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1.
J Asthma Allergy ; 17: 495-516, 2024.
Article in English | MEDLINE | ID: mdl-38828396

ABSTRACT

Asthma is a high-risk disease based on airway hyperresponsiveness (AHR). In this review, we found that there are many studies on clinical therapy for asthma that focus on the efficacy of acupuncture therapy and its mechanisms, including the functional connectivity of different brain regions, with the aid of functional magnetic resonance imaging (fMRI), immune responses/cell recognition (innate lymphoid cells and balance of Th1/Th2 and Treg/Th17), intracellular mechanism (autophagy, endoplasmic reticulum stress, and epigenetic alteration), and ligand-receptor/chemical signaling pathway (neurotransmitter, hormone, and small molecules). In this review, we summarized the clinical and experimental evidence for the mechanisms of acupuncture therapy in asthma to offer insights into drug discovery and clinical therapy. Given the paucity of clinical studies on the mechanisms of acupuncture in the treatment of asthma, this review notably included studies based on animal models to investigate the mechanisms of acupuncture in the treatment of asthma.

2.
Sci Rep ; 14(1): 12659, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830942

ABSTRACT

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The "Atyp.C" parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case-control study identified clinical primary or newly recurrent BC (study period, 2022-2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman's rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.


Subject(s)
Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/urine , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Male , Female , Risk Factors , Aged , Middle Aged , Retrospective Studies , Case-Control Studies , Cell Nucleus
3.
Front Bioeng Biotechnol ; 12: 1367929, 2024.
Article in English | MEDLINE | ID: mdl-38832128

ABSTRACT

Introduction: Surface electromyogram (sEMG) signals have been widely used in human upper limb force estimation and motion intention recognition. However, the electrocardiogram(ECG) artifact generated by the beating of the heart is a major factor that reduces the quality of the EMG signal when recording the sEMG signal from the muscle close to the heart. sEMG signals contaminated by ECG artifacts are difficult to be understood correctly. The objective of this paper is to effectively remove ECG artifacts from sEMG signals by a novel method. Methods: In this paper, sEMG and ECG signals of the biceps brachii, brachialis, and triceps muscle of the human upper limb will be collected respectively. Firstly, an improved multi-layer wavelet transform algorithm is used to preprocess the raw sEMG signal to remove the background noise and power frequency interference in the raw signal. Then, based on the theory of blind source separation analysis, an improved Fast-ICA algorithm was constructed to separate the denoising signals. Finally, an ECG discrimination algorithm was used to find and eliminate ECG signals in sEMG signals. This method consists of the following steps: 1) Acquisition of raw sEMG and ECG signals; 2) Decoupling the raw sEMG signal; 3) Fast-ICA-based signal component separation; 4) ECG artifact recognition and elimination. Results and discussion: The experimental results show that our method has a good effect on removing ECG artifacts from contaminated EMG signals. It can further improve the quality of EMG signals, which is of great significance for improving the accuracy of force estimation and motion intention recognition tasks. Compared with other state-of-the-art methods, our method can also provide the guiding significance for other biological signals.

5.
Front Cell Dev Biol ; 12: 1359451, 2024.
Article in English | MEDLINE | ID: mdl-38694823

ABSTRACT

Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.

6.
Quant Imaging Med Surg ; 14(5): 3619-3627, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38720849

ABSTRACT

Background: Cardiac ultrasound is one of the most important examinations in cardiovascular medicine, but the technical requirements for the operator are relatively high, which to some extent affects the scope of its use. This study was dedicated to investigating the agreement of ejection fraction between coronary computed tomography (CT) and cardiac ultrasound and diagnostic performance in evaluating the clinical diagnosis of patients with chronic heart failure. Methods: We conducted a single-center-based retrospective study including 343 consecutive patients enrolled between January 2019 to April 2020, all of whom presented with suspected symptoms of heart failure within one month. All enrolled cases performed cardiac ultrasound and coronary CT scans. The CT images were analyzed using accurate left ventricle (AccuLV) artificial intelligence (AI) software to calculate the ejection fraction-computed tomography (EF-CT) and it was compared with the ejection fraction (EF) obtained based on ultrasound. Cardiac insufficiency was determined if the EF measured by ultrasound was below 50%. Diagnostic performance analysis, correlation analysis and Bland-Altman plot were used to compare agreement between EF-CT and CT. Results: Of the 319 successfully performed patients, 220 (69%) were identified as cardiac insufficiency. Quantitative consistency analysis showed a good correlation between EF-CT and EF values in all cases (R square =0.704, r=0.837). Bland-Altman analysis showed mean bias of 6.6%, mean percentage error of 27.5% and 95% limit of agreement of -17% to 30% between EF and EF-CT. The results of the qualitative diagnostic study showed that the sensitivity and specificity of EF measured by coronary CT reached a high level of 91% [95% confidence interval (CI): 86-94%], and the positive diagnostic value was up to 96% (95% CI: 92-98%). Conclusions: The EF-CT and EF have excellent agreement, and AccuLV-based AI left ventricular function analysis software perhaps can be used as a clinical diagnostic reference.

7.
Cancer Biol Med ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38712819

ABSTRACT

OBJECTIVE: To investigate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). METHODS: A total of 155 patients with CHB-related HCC who received ICI-based therapy (in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were evaluated. Patients were divided into two groups: MASLD concurrent with CHB [MASLD-CHB] (n = 38), and CHB (n = 117). RESULTS: The median progression-free survival (PFS, 6.9 months vs. 9.3 months; P = 0.001), progressive disease (57.89% vs. 37.61%; P = 0.028), and disease control rate (42.11% vs. 62.39%; P = 0. 028) in the MASLD-CHB group were significantly worse than the CHB group. The median overall survival was not attained. The percentage of CD4+PD1+ (17. 56% vs. 8.89%; P < 0.001) and CD8+PD1+ T cells (10.50% vs. 7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB group. Concurrent MASLD [hazard ratio (HR) = 1.921; 95% CI, 1.138-3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment (HR = 2.412; 95% CI, 1.360-4.279; P = 0.003) were independent risk factors for PFS in all patients. CONCLUSIONS: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

9.
Nature ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750366

ABSTRACT

Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity1,2. However, its impact is often overlooked in biophysical studies that are typically performed at non-physiological temperatures, potentially leading to inaccurate mechanistic and pharmacological insights. Here we demonstrate temperature-dependent changes in the structure and function of TRPM4, a temperature-sensitive Ca2+-activated ion channel3-7. By studying TRPM4 prepared at physiological temperature using single-particle cryo-electron microscopy, we identified a 'warm' conformation that is distinct from those observed at lower temperatures. This conformation is driven by a temperature-dependent Ca2+-binding site in the intracellular domain, and is essential for TRPM4 function in physiological contexts. We demonstrated that ligands, exemplified by decavanadate (a positive modulator)8 and ATP (an inhibitor)9, bind to different locations of TRPM4 at physiological temperatures than at lower temperatures10,11, and that these sites have bona fide functional relevance. We elucidated the TRPM4 gating mechanism by capturing structural snapshots of its different functional states at physiological temperatures, revealing the channel opening that is not observed at lower temperatures. Our study provides an example of temperature-dependent ligand recognition and modulation of an ion channel, underscoring the importance of studying macromolecules at physiological temperatures. It also provides a potential molecular framework for deciphering how thermosensitive TRPM channels perceive temperature changes.

10.
J Vasc Access ; : 11297298241250263, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752401

ABSTRACT

BACKGROUND: Assessing the size of the distal radial artery (DRA) in anatomic snuffbox (AS) before coronary intervention is extremely important in the selection of suitable patients, improving the success rate of puncture and reducing the complications. OBJECTIVE: To evaluate the diameter of the DRA in AS and its influencing factors in Chinese patients scheduled for coronary intervention. METHODS: Ultrasound was used to detect the inner diameter of vessels. A total of 1182 patients were involved in the study. RESULTS: In all patients, the mean inner diameters of the DRA, conventional radial artery (CRA) and ulnar artery (UA) were 2.00 ± 0.43 mm, 2.38 ± 0.51 mm and 1.99 ± 0.47 mm, respectively. The proportion of DRA diameter ⩾2.0 mm was 53% (in all patients), 64% (in males), 36% (in females), respectively. The DRA/CRA ratios were 0.85 ± 0.13 in all patients, 0.86 ± 0.13 in males and 0.84 ± 0.13 in females. The diameter of the DRA was strongly positively correlated with the diameter of the CRA (r = 0.750, p < 0.05), and weakly correlated with the body mass index (r = 0.303, p < 0.05) and the diameter of the UA (r = 0.304, p < 0.05). Multivariate regression analysis showed that female sex, age ⩾60 years, body mass index <24 kg/m2, previous CRA/DRA access and history of coronary artery disease were independent predictors of the DRA diameter <2.0 mm. CONCLUSION: Measurement of the diameter of the DRA by ultrasonography may offer important information prior to coronary catheterization.

11.
Chemistry ; : e202400803, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752562

ABSTRACT

To meet the demand for higher energy density in lithium-ion batteries and expand their application range, coupling lithium metal anodes with high-voltage cathodes is an ideal solution. However, the compatibility between lithium metal batteries and electrolytes affects their applicability. In this study, proposes a locally concentrated electrolyte based on ethyl acetate (EA) as the solvent, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) as the lithium salt, and lithium difluorooxoborate (LiDFOB) as a sacrificial agent to enhance the low-temperature and high-voltage endurance of Li//Lithium cobalt oxide (LCO) batteries. The Li//LCO battery can operate within the voltage range of 3 to 4.5 V, with an initial discharge specific capacity of 174.5 mAh g-1 at 20 oC. At -40 oC, after 200 cycles, the capacity retention rate is 87.7%. It can operate under extreme conditions of -70 oC, with a discharge specific capacity of 112.6 mAh g-1. Additionally, LCO//HC batteries using this electrolyte demonstrate excellent performance. Present work provides a new perspective for the optimization of electrolytes for low-temperature lithium-ion batteries.

12.
Case Rep Oncol Med ; 2024: 7925511, 2024.
Article in English | MEDLINE | ID: mdl-38770355

ABSTRACT

Background: Delayed migration and exposure of embolic coils is a rare complication of endovascular therapy for carotid blowout syndrome. Methods: A 64-year-old man with recurrent tongue cancer noticed the presence of foreign body in the malignant wound on the right side of his neck. He had undergone transarterial embolization on his right vertebral artery, right common carotid artery (CCA), and internal carotid artery (ICA) for carotid blowout syndrome 1 month prior. On physical examination, exposed spring-like metallic coils were observed, covered in brownish granulation tissue, at the bottom of the malignant wound. Neck radiograph and computed tomography confirmed the extrusion and migration of the embolic coils. Results: In this case, the patient was managed by transection of the exposed coils at the wound surface with close monitoring. Conclusions: Computed tomography angiography is essential for assessing the condition of the remaining embolic coils. In cases with thrombosed parent arteries, a conservative approach, like the transection of exposed coils, can be employed as part of the management strategy.

13.
Med Biol Eng Comput ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775870

ABSTRACT

The current diagnosis of diabetic retinopathy is based on fundus images and clinical experience. However, considering the ineffectiveness and non-portability of medical devices, we aimed to develop a diagnostic model for diabetic retinopathy based on glucose series data from the wearable continuous glucose monitoring system. Therefore, this study developed a novel method, i.e., double deep latent autoencoder, for exploring glycemic variability influence from multi-day glucose data for diabetic retinopathy. Specifically, the model proposed in this research could encode continuous glucose sensor data with non-continuous and variable length via the integration of a data reorganization module and a novel encoding module with fragmented-missing-wise objective function. Additionally, the model implements a double deep autoencoder, which integrated convolutional neural network, long short-term memory, to jointly capturing the inter-day and intra-day glucose latent features from glucose series. The effectiveness of the proposed model is evaluated through a cross-validation method to clinical datasets of 765 type 2 diabetes patients. The proposed method achieves the highest accuracy value (0.89), precision value (0.88), and F1 score (0.73). The results suggest that our model can be used to remotely diagnose and screen for diabetic retinopathy by learning potential features of glucose series data collected by wearable continuous glucose monitoring systems.

14.
Science ; 384(6698): 920-928, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38781377

ABSTRACT

Excitatory and inhibitory synapses do not overlap even when formed on one submicron-sized dendritic protrusion. How excitatory and inhibitory postsynaptic cytomatrices or densities (e/iPSDs) are segregated is not understood. Broadly, why membraneless organelles are naturally segregated in cellular subcompartments is unclear. Using biochemical reconstitutions in vitro and in cells, we demonstrate that ePSDs and iPSDs spontaneously segregate into distinct condensed molecular assemblies through phase separation. Tagging iPSD scaffold gephyrin with a PSD-95 intrabody (dissociation constant ~4 nM) leads to mistargeting of gephyrin to ePSD condensates. Unexpectedly, formation of iPSD condensates forces the intrabody-tagged gephyrin out of ePSD condensates. Thus, instead of diffusion-governed spontaneous mixing, demixing is a default process for biomolecules in condensates. Phase separation can generate biomolecular compartmentalization specificities that cannot occur in dilute solutions.


Subject(s)
Biomolecular Condensates , Carrier Proteins , Membrane Proteins , Membrane Proteins/metabolism , Membrane Proteins/chemistry , Animals , Biomolecular Condensates/chemistry , Biomolecular Condensates/metabolism , Carrier Proteins/metabolism , Carrier Proteins/chemistry , Humans , Post-Synaptic Density/metabolism , Disks Large Homolog 4 Protein/metabolism , HEK293 Cells , Synapses/physiology , Phase Separation
15.
Cancer ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38781433

ABSTRACT

BACKGROUND: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. METHODS: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. RESULTS: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. CONCLUSIONS: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

16.
Zool Res ; 45(3): 633-647, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38766746

ABSTRACT

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.


Subject(s)
Nociception , Parabrachial Nucleus , Animals , Parabrachial Nucleus/physiology , Mice , Nociception/physiology , Neurons/physiology , Pain/physiopathology , Male , Behavior, Animal/physiology
17.
Diabetes Metab Res Rev ; 40(4): e3813, 2024 May.
Article in English | MEDLINE | ID: mdl-38767128

ABSTRACT

AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Female , Male , Middle Aged , Blood Glucose/analysis , Follow-Up Studies , Prospective Studies , Risk Factors , Prognosis , Aged , Glycated Hemoglobin/analysis , Blood Glucose Self-Monitoring , Cause of Death , Biomarkers/analysis , Biomarkers/blood , Circadian Rhythm/physiology , Hypoglycemia/mortality , Survival Rate , Adult
18.
Bioorg Med Chem ; 106: 117754, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38728869

ABSTRACT

To improve the biodistribution of the drug in the tumor, a supramolecular prodrug of SN38 was fabricated in situ between endogenous albumin and SN38 prodrug modified with semaglutide side chain. Firstly, SN38 was conjugated with semaglutide side chain and octadecanedioic acid via glycine linkers to obtain SI-Gly-SN38 and OA-Gly-SN38 prodrugs, respectively. Both SI-Gly-SN38 and OA-Gly-SN38 exhibited excellent stability in PBS for over 24 h. Due to the strong binding affinity of the semaglutide side chain with albumin, the plasma half-life of SI-Gly-SN38 was 2.7 times higher than that of OA-Gly-SN38. Furthermore, with addition of HSA, the fluorescence intensity of SI-Gly-SN38 was 4 times higher than that of OA-Gly-SN38, confirming its strong binding capability with HSA. MTT assay showed that the cytotoxicity of SI-Gly-SN38 and OA-Gly-SN38 was higher than that of Irinotecan. Even incubated with HSA, the SI-Gly-SN38 and OA-Gly-SN38 still maintained high cytotoxicity, indicating minimal influence of HSA on their cytotoxicity. In vivo pharmacokinetic studies demonstrated that the circulation half-life of SI-Gly-SN38 was twice that of OA-Gly-SN38. SI-Gly-SN38 exhibited significantly reduced accumulation in the lungs, being only 0.23 times that of OA-Gly-SN38. The release of free SN38 in the lungs from SI-Gly-SN38 was only 0.4 times that from OA-Gly-SN38 and Irinotecan. The SI-Gly-SN38 showed the highest accumulation in tumors. The tumor inhibition rate of SI-Gly-SN38 was 6.42% higher than that of OA-Gly-SN38, and 8.67% higher than that of Irinotecan, respectively. These results indicate that the supramolecular prodrug delivery system can be constructed between SI-Gly-SN38 and endogenous albumin, which improves drug biodistribution in vivo, enhances tumor accumulation, and plays a crucial role in tumor growth inhibition.


Subject(s)
Irinotecan , Prodrugs , Irinotecan/chemistry , Irinotecan/pharmacology , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/chemical synthesis , Animals , Humans , Mice , Tissue Distribution , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacokinetics , Molecular Structure , Drug Screening Assays, Antitumor , Cell Proliferation/drug effects , Cell Line, Tumor , Mice, Inbred BALB C , Mice, Nude , Albumins/chemistry , Male , Structure-Activity Relationship , Serum Albumin, Human/chemistry , Glucagon-Like Peptides
19.
Arthroscopy ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38735417

ABSTRACT

PURPOSES: To evaluate if the modified suture button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, data of patients who underwent the modified suture button Latarjet with CAL and PM preservation in our department was collected. The glenoid bone loss of these patients were above 20% or over 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of the preoperative 3-dimensional computed tomography (3D CT) evaluation of the glenoid defect area (GDA) and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was utilized to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3D CT, and magnetic resonance imaging (MRI) was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was: VAS 85.71%; ASES 97.14%; Rowe 100%; Walch-Duplay 97.14%. 33 patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3±2.2 months, and the coracoid grafts restored 97.1±4.0% of the perfect fitting circle (PFC) at the last follow-up. Postoperative CT scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial majority of patients (>85%) achieved the MCID for the VAS, ASES, ROWE, and Walch-Duplay scores. Additionally, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up.

20.
Langmuir ; 40(19): 9999-10007, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38696767

ABSTRACT

With a large theoretical capacity and high energy density, aluminum-air batteries are a promising energy storage device. However, the rigid structure and liquid electrolyte of a traditional aluminum-air battery limit its application potential in the field of flexible electronics, and the irreversible corrosion of its anode greatly reduces the battery life. To solve the above problems, a PVA/KC/KOH (2 M) composite gel polymer electrolyte (GPE) with a three-dimensional dual-network structure consisting of polyvinyl alcohol (PVA), kappa-carrageenan (KC), and potassium hydroxide was prepared in this paper by a simple two-step method and applied in aluminum-air batteries. At room temperature, the ionic conductivity of the PVA/KC/KOH (2 M) composite GPE was found to be up to 6.50 × 10-3 S cm-1. By utilizing this composite GPE, a single flexible aluminum-air battery was assembled and achieved a maximum discharge voltage of 1.2 V at 5 mA cm-2, with discharge time exceeding 3 h. Moreover, the single flexible aluminum-air battery maintains good electrochemical performance under various deformation modes, and the output voltage of the battery remains at about 99% after 300 cycles. The construction of flexible aluminum-air batteries based on a three-dimensional dual-network PVA/KC/KOH composite GPE provides excellent safety and high-multiplication capabilities for aluminum-air batteries, making them potential candidates for various flexible device applications.

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