Balancing the Kinetic and Thermodynamic Synergetic Effect of Doped Carbon Molecular Sieves for Selective Separation of C2H4/C2H6.

Selective separation of ethylene and ethane (C2H4/C2H6) is a formidable challenge due to their close molecular size and boiling point. Compared to industry-used cryogenic distillation, adsorption separation would offer a more energy-efficient solution when an efficient adsorbent is available. Herein, a class of C2H4/C2H6 separation adsorbents, doped carbon molecular sieves (d-CMSs) is reported which are prepared from the polymerization and subsequent carbonization of resorcinol, m-phenylenediamine, and formaldehyde in ethanol solution. The study demonstrated that the polymer precursor themselves can be a versatile platform for modifying the pore structure and surface functional groups of their derived d-CMSs. The high proportion of pores centered at 3.5 Å in d-CMSs contributes significantly to achieving a superior kinetic selectivity of 205 for C2H4/C2H6 separation. The generated pyrrolic-N and pyridinic-N functional sites in d-CMSs contribute to a remarkable elevation of Henry selectivity to 135 due to the enhancement of the surface polarity in d-CMSs. By balancing the synergistic effects of kinetics and thermodynamics, d-CMSs achieve efficient separation of C2H4/C2H6. Polymer-grade C2H4 of 99.71% purity can be achieved with 75% recovery using the devised d-CMSs as reflected in a two-bed vacuum swing adsorption simulation.

[Advances in the Treatment of Osteochondral Lesions of the Talus]. / è·éª¨éª¨è½¯éª¨æŸä¼¤æ²»ç–—çš„ç ”ç©¶è¿›å±•.

Osteochondral lesion of the talus (OLT) is a localized cartilage and subchondral bone injury of the talus trochlea. OLT is caused by trauma and other reasons, including osteochondritis dissecans of the talus (OCD) and talus osteochondral tangential fracture. OLT can develop from being asymptomatic to subchondral bone cysts accompanied by deep ankle pain. OLT tends to occur on the medial and lateral sides of the talar vault. OLT seriously affects the patients' life and work and may even lead to disability. Herein, we reviewed advances in the treatment of OLT and the strengths and weaknesses of various treatments. Different treatment methods, including conservative treatments and surgical treatments, can be adopted according to the different subtypes or clinical symptoms of OLT. Conservative treatments mostly relieve symptoms in the short term and only slow down the disease. In recent years, it has been discovered that platelet-rich plasma injection, microfracture, periosteal bone grafting, talar cartilage transplantation, allograft bone transplantation, reverse drilling under robotic navigation, and other methods can achieve considerable benefits when each of these treatment methods is applied. Furthermore, microfracture combined with platelet-rich plasma injections, microfracture combined with cartilage transplantation, and various other treatment methods combined with anterior talofibular ligament repair have all led to good treatment outcomes.

Eu(III) functionalized ZnMOF based efficient dual-emission sensor integrated with self-calibrating logic gate for intelligent detection of epinephrine.

The rapid detection of epinephrine (EPI) in serum holds immense importance in the early disease diagnosis and regular monitoring. On the basis of the coordination post-synthetic modification (PSM) strategy, a Eu3+ functionalized ZnMOF (Eu3+@ZnMOF) was fabricated by anchoring the Eu3+ ions within the microchannels of ZnMOF as secondary luminescent centers. Benefiting from two independent luminescent centers, the prepared Eu3+@ZnMOF shows great potential as a multi-signal self-calibrating luminescent sensor in visually and efficiently detecting serum EPI levels, with high reliability, fast response time, excellentrecycleability, and low detection limits of 17.8 ng/mL. Additionally, an intelligent sensing system was designed in accurately and reliably detecting serum EPI levels, based on the designed self-calibrating logic gates. Furthermore, the possible sensing mechanisms were elucidated through theoretical calculations as well as spectral overlaps. This work provides an effective and promising strategy for developing MOFs-based self-calibrating intelligent sensing platforms to detect bioactive molecules in bodily fluids.

Ion channel-mediated mitochondrial volume regulation and its relationship with mitochondrial dynamics.

The mitochondrion, one of the important cellular organelles, has the major function of generating adenosine triphosphate and plays an important role in maintaining cellular homeostasis, governing signal transduction, regulating membrane potential, controlling programmed cell death and modulating cell proliferation. The dynamic balance of mitochondrial volume is an important factor required for maintaining the structural integrity of the organelle and exerting corresponding functions. Changes in the mitochondrial volume are closely reflected in a series of biological functions and pathological changes. The mitochondrial volume is controlled by the osmotic balance between the cytoplasm and the mitochondrial matrix. Thus, any disruption in the influx of the main ion, potassium, into the cells can disturb the osmotic balance between the cytoplasm and the matrix, leading to water movement between these compartments and subsequent alterations in mitochondrial volume. Recent studies have shown that mitochondrial volume homeostasis is closely implicated in a variety of diseases. In this review, we provide an overview of the main influencing factors and research progress in the field of mitochondrial volume homeostasis.

RNAi silencing CHS1 gene shortens the mortality time of Plutella xylostella feeding Bt-transgenic Brassica napus.

BACKGROUND: Insect-resistance genetically modified (GM) plants derived from Bacillus thuringiensis (Bt) have been cultivated to control pests, but continuous cultivation of Bt-transgenic plants at large-scale regions leads to the resistance evolution of target insects to transgenic plants. RNA interference (RNAi) technology is considered an effective strategy in delaying the resistance evolution of target insects. RESULTS: We here developed a single transgenic oilseed rape (Brassica napus) line with hairpin RNA of the chitin-synthase 1 gene (CHS1) of Plutella xylostella (hpPxCHS1) and a pyramid transgenic B. napus line harboring hpPxCHS1 and Bt gene (Cry1Ac). Escherichia coli HT115 delivered hpPxCHS1 showed negative effects on the growth of P. xylostella. The single transgenic and pyramid transgenic B. napus significantly reduced the larval weight and length of P. xylostella and increased its lethality rate, with down-regulation expression of the PxCHS1 gene in insects. CONCLUSION: Compared to Bt-transgenic B. napus, pyramid-transgenic B. napus shorted the mortality time of P. xylostella, indicating that RNAi technology synergistic with Bt protein improves the effectiveness of controlling target insects. Our results proved that RNAi can delay the resistance evolution of target insects to Bt-transgenic plants. © 2024 Society of Chemical Industry.

Heterometallic ZnHoMOF as a Dual-Responsive Luminescence Sensor for Efficient Detection of Hippuric Acid Biomarker and Nitrofuran Antibiotics.

Developing efficient and sensitive MOF-based luminescence sensors for bioactive molecule detection is of great significance and remains a challenge. Benefiting from favorable chemical and thermal stability, as well as excellent luminescence performance, a porous Zn(II)Ho(III) heterometallic-organic framework (ZnHoMOF) was selected here as a bifunctional luminescence sensor for the early diagnosis of a toluene exposure biomarker of hippuric acid (HA) through "turn-on" luminescence enhancing response and the daily monitoring of NFT/NFZ antibiotics through "turn-off" quenching effects in aqueous media with high sensitivity, acceptable selectivity, good anti-interference, exceptional recyclability performance, and low detection limits (LODs) of 0.7 ppm for HA, 0.04 ppm for NFT, and 0.05 ppm for NFZ. Moreover, the developed sensor was employed to quantify HA in diluted urine samples and NFT/NFZ in natural river water with satisfactory results. In addition, the sensing mechanisms of ZnHoMOF as a dual-response chemosensor in efficient detection of HA and NFT/NFZ antibiotics were conducted from the view of photo-induced electron transfer (PET), as well as inner filter effects (IFEs), with the help of time-dependent density functional theory (TD-DFT) and spectral overlap experiments.

Added value of CE-CT radiomics to predict high Ki-67 expression in hepatocellular carcinoma.

BACKGROUND: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. METHODS: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). CONCLUSIONS: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.

An edge-based approach for virtual network embedding based on the graph edit distance.

Virtualization and resource isolation techniques have enabled the efficient sharing of networked resources. How to control network resource allocation accurately and flexibly has gradually become a research hotspot due to the growth in user demands. Therefore, this paper presents a new edge-based virtual network embedding approach to studying this problem that employs a graph edit distance method to accurately control resource usage. In particular, to manage network resources efficiently, we restrict the use conditions of network resources and restrict the structure based on common substructure isomorphism and an improved spider monkey optimization algorithm is employed to prune redundant information from the substrate network. Experimental results showed that the proposed method achieves better performance than existing algorithms in terms of resource management capacity, including energy savings and the revenue-cost ratio.

Salt-assisted surface charge driven synthesis of large pores alumina as carbon tolerance support for propane dehydrogenation.

Porous alumina has been widely used as catalytic support for industrial processes. Under carbon emission constraints, developing a low-carbon porous aluminum oxide synthesis method is a long-standing challenge for low-carbon technology. Herein, we report a method involving the only use of elements of the aluminum-containing reactants (e.g. sodium aluminate and aluminum chloride), sodium chloride was introduced as the coagulation electrolyte to adjust the precipitation process. Noticeably, the adjustment of the dosages of NaCl would allow us to tailor the textural properties and surface acidity with a volcanic-type change of the assembled alumina coiled plates. As a result, porous alumina with a specific surface area of 412 m2/g, large pore volume of 1.96 cm3/g, and concentrated pore size distribution at 30 nm was obtained. The function of salt on boehmite colloidal nanoparticles was proven by colloid model calculation, dynamic light scattering, and scanning/transmission electron microscopy. Afterward, the synthesized alumina was loaded with PtSn to prepare catalysts for the propane dehydrogenation reaction. The obtained catalysts were active but showed different deactivation behavior that was related to the coke resistance capability of the support. We figure out the correlation between pore structure and the activity of the PtSn catalysts associated with the maximum conversion of 53 % and minimum deactivation constant occurring at the pore diameter around 30 nm of the porous alumina. This work offers new insight into the synthesis of porous alumina.

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

Soft Carbon as Cathode with High Rate Performance for Dual-Ion Batteries via Fast PF6 - Intercalation Improved by Surface Effect.

Dual-ion battery is a new type of battery in which both anions and cations participate in the energy storage process. However, this unique battery configuration imposes high requirements on the cathode, which typically presents a poor rate performance due to the sluggish diffusion dynamics and intercalation reaction kinetics of anions. Herein, we report petroleum coke-based soft carbon as the cathode for dual-ion batteries, exhibiting a superior rate performance with a specific capacity of 96 mAh g-1 at a rate of 2 C and 72 mAh g-1 remained even at 50 C. In situ XRD and Raman demonstrate that the anions can directly form lower-stage graphite intercalation compounds during the charge process owing to the surface effect, skipping the long evolutionary process from higher to lower stage, thus significantly improving the rate performance. This study highlights the impact of the surface effect and provides a promising perspective for dual-ion batteries.

Nanoengineered Design of inside-Heating Hot Nanoreactor Surrounded by Cool Environment for Selective Hydrogenations.

Catalysts with designable intelligent nanostructure may potentially drive the changes in chemical reaction techniques. Herein, a multi-function integrating nanocatalyst, Pt-containing magnetic yolk-shell carbonaceous structure, having catalysis function, microenvironment heating, thermal insulation, and elevated pressure into a whole is designed, which induces selective hydrogenation within heating-constrained nanoreactors surrounded by ambient environment. As a demonstration, carbonyl of α, ß-unsaturated aldehydes/ketones are selectively hydrogenated to unsaturated alcohols with a >98% selectivity at a nearly complete conversion under mild conditions of 40 °C and 3 bar instead of harsh requirements of 120 °C and 30 bar. It is creatively demonstrated that the locally increased temperature and endogenous pressure (estimated as ≈120 °C, 9.7 bar) in the nano-sized space greatly facilitate the reaction kinetics under an alternating magnetic field. The outward-diffused products to the "cool environment" remain thermodynamically stable, avoiding the over-hydrogenation that often occurs under constantly heated conditions of 120 °C. Regulation of the electronic state of Pt by sulfur doping of carbon allows selective chemical adsorption of the CO group and consequently leads to selective hydrogenation. It is expected that such a multi-function integrated catalyst provides an ideal platform for precisely operating a variety of organic liquid-phase transformations under mild reaction conditions.

Clinical significance of serum levels of 14-3-3ß protein in patients with stable chronic obstructive pulmonary disease.

Nowadays, the diagnosis and treatment of COPD are often based on the results of lung function tests. Certain individuals, however, are not candidates for lung function testing due to pulmonary bullae, cardiac failure, low lung function, and other factors. Therefore, we evaluated whether serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein ß (14-3-3ß) could be a biomarker for the diagnosis of stable COPD patients. The expression of serum 14-3-3ß protein was evaluated by an enzyme-linked immunosorbent assay. The association between its concentrations and clinical parameters of stable COPD patients were analyzed by correlation analysis and ROC curve. The results before propensity score matching (PSM) showed that serum 14-3-3ß protein concentrations (ng/ml) in stable COPD patients were significantly higher than in healthy controls (P < 0.001). Furthermore, serum 14-3-3ß protein concentrations were higher in GOLD 3&4 COPD patients compared with healthy participants, GOLD 1 and GOLD 2 COPD patients (P < 0.05), which shows that the concentration of 14-3-3ß protein correlates with disease severity in stable COPD patients. After 1:1 PSM, there was also a statistically significant rise in 14-3-3 protein levels in stable COPD patients compared to healthy controls (P < 0.01). Serum 14-3-3ß protein levels were positively correlated with blood neutrophil levels (P < 0.05), and negatively related to lung function parameters in stable COPD patients (P < 0.01). When the cutoff value was set at 29.53 ng/ml, the ROC curve yielded a sensitivity of 84.9% and a specificity of 68.3% for diagnosing stable COPD. The 14-3-3ß protein may be a potential serum biomarker for the diagnosis of stable COPD patients, which is associated with disease severity, systemic inflammation, and small airway obstruction.

Chemorobust dye-encapsulated framework as dual-emission self-calibrating ratiometric sensor for intelligent detection of toluene exposure biomarker in urine.

By taking advantages of confinement effect can effectively prevent dye aggregation caused luminescent quenching, Eosin Y (EY) was encapsulated into a chemorobust porous CoMOF as secondary fluorescent signal to construct the dual-emitting sensor of EY@CoMOF. And the photo-induced electron transfer from CoMOF to EY molecules induced EY@CoMOF presenting a weak blue emission at 421 nm and a strong yellow emission at 565 nm. Those dual-emission features also endow EY@CoMOF itself great potentials as a self-calibrating ratiometric sensor in visually and efficiently monitoring hippuric acid (HA) in urine, with fast response, high sensitivity and selectivity, excellent recyclable, and low LOD (0.24 µg/mL). Furthermore, based on a tandem combinational logic gate, an intelligent detection system was designed to improve the practicability and convenience of HA detection in urine. To the best of our knowledge, this is the first example of dye@MOF based sensor for HA detection. And this work provides a promising approach for developing dye@MOF based sensors to intelligent detect bioactive molecules.

Boosting Selective Oxidation of Ethylene to Ethylene Glycol Assisted by In situ Generated H2 O2 from O2 Electroreduction.

Ethylene glycol is a useful organic compound and chemical intermediate for manufacturing various commodity chemicals of industrial importance. Nevertheless, the production of ethylene glycol in a green and safe manner is still a long-standing challenge. Here, we established an integrated, efficient pathway for oxidizing ethylene into ethylene glycol. Mesoporous carbon catalyst produces H2 O2 , and titanium silicalite-1 catalyst would subsequently oxidize ethylene into ethylene glycol with the in situ generated H2 O2 . This tandem route presents a remarkable activity, i.e., 86 % H2 O2 conversion with 99 % ethylene glycol selectivity and 51.48 mmol gecat -1 h-1 production rate at 0.4 V vs. reversible hydrogen electrode. Apart from generated H2 O2 as an oxidant, there exists ⋅OOH intermediate which could omit the step of absorbing and dissociating H2 O2 over titanium silicalite-1, showing faster reaction kinetics compared to the ex situ one. This work not only provides a new idea for yielding ethylene glycol but also demonstrates the superior of in situ generated H2 O2 in tandem route.

Efficient catalysts of surface hydrophobic Cu-BTC with coordinatively unsaturated Cu(I) sites for the direct oxidation of methane.

Selective oxidation of methane to organic oxygenates over metal-organic frameworks (MOFs) catalysts at low temperature is a challenging topic in the field of C1 chemistry because of the inferior stability of MOFs. Modifying the surface of Cu-BTC via hydrophobic polydimethylsiloxane (PDMS) at 235 °C under vacuum not only can dramatically improve its catalytic cycle stability in a liquid phase but also generate coordinatively unsaturated Cu(I) sites, which significantly enhances the catalytic activity of Cu-BTC catalyst. The results of spectroscopy characterizations and theoretical calculation proved that the coordinatively unsaturated Cu(I) sites made H2O2 dissociative into •OH, which formed Cu(II)-O active species by combining with coordinatively unsaturated Cu(I) sites for activating the C-H bond of methane. The high productivity of C1 oxygenates (CH3OH and CH3OOH) of 10.67 mmol gcat.-1h-1 with super high selectivity of 99.6% to C1 oxygenates was achieved over Cu-BTC-P-235 catalyst, and the catalyst possessed excellent reusability.

Eu(III)-Functionalized MOF-Based Dual-Emission Ratiometric Sensor Integrated with Logic Gate Operation for Efficient Detection of Hippuric Acid in Urine and Serum.

With the introduction of Eu3+ ions as the secondary fluorescent signal reporter and sensing active sites, a dual-emission ratiometric sensor of Eu3+@NiMOF (Eu3+ functional NiMOF) for hippuric acid (HA) detection in urine and serum was fabricated via the postsynthetic encapsulating strategy. Based on the two emission signals at 441 nm (turn-on) and 628 nm (turn-off), the produced Eu3+@NiMOF ratiometric sensor provided enhanced sensitivity, higher selectivity, and 9.7 times lower limits of detection (LOD) for the detection of HA (2.38 µM, 0.42 µg·mL-1) than that of the pristine NiMOF. Considering the high sensitivity and visualization results, further exploration of intelligent applications in the HA sensing process was carried out by constructing a tandem combinational logic gate to improve the practicability and convenience with the help of a smartphone. This work provides a promising approach for developing MOF-based ratiometric sensors to detect biomarkers.

LncRNA AC108925 promotes osteoblast differentiation of tendon-derived stem cells by targeting miR-146a-3p.

It has been reported that tendon-derived stem cells(TDSCs) conduce to the ostosis in tendon diseases, and the molecular mechanism needs to be discussed. To investigate the function and mechanism of LncRNA in tendinopathy. Tendon of tendinopathy patients and health controls were obtained, and sequencing analysis have been performed to detect the significantly expressed genes and non-coding RNAs. Moreover, to further discuss LncRNA AC108925 in tendinopathy, tendinopathy animal models have been established, and the expression of LncRNA AC108925 expression was examined by RT-qPCR methods. Furthermore, hTDSCs have been treated by osteogenic medium, and the modulating function of LncRNA AC108925 on the osteoblast differentiation of hTDSCs have been examined. Sequencing analysis showed that AC108925 a dramatically elevated LncRNA, and results of animal and cells studies confirmed the finding. Knockdown AC108925 inhibited the osteogenic differentiation of osteogenic medium treated TDSCs by decreasing the expression of osteogenic markers. Furthermore, miR-146a-3p is a target of AC108925 in TDSCs, and miR-146a-3p is a negative modulator of osteogenic differentiation of hTDSCs by inhibiting the effects of AC108925 shRNA on osteogenic differentiation of hTDSCs. AC108925 can regulate the osteogenic differentiation of hTDSCs via regulating the miR-146a-3p. Targeting the AC108925/miR-146a-3p axis might be a latent way to treat tendinopathy.

Randomized, double-blind, noninferiority study of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily in patients with acute ankle sprain.

BACKGROUND: Diclofenac diethylamine (DDEA) gel has demonstrated efficacy for treatment of ankle sprains in both the 1.16% four-times-daily (QID) and 2.32% twice-daily (BID) formulations. The objective of this study was to compare, for the first time, the efficacy of DDEA 2.32% gel BID and DDEA 1.16% gel QID. METHODS: This was a phase 3, randomized, double-blind, multicenter, active-controlled, parallel-group study conducted in China from October 2019 to November 2020, designed to determine the noninferiority of DDEA 2.32% gel BID relative to DDEA 1.16% gel QID for treatment of grade I-II ankle sprain. At study entry, patients must have had pain on movement (POM) ≥50 mm on a 100-mm visual analogue scale (VAS), and not received any pain medication. The primary efficacy endpoint was the noninferiority of DDEA 2.32% gel BID vs DDEA 1.16% gel QID for POM as assessed by the patient using the 100-mm VAS, conducted on day 5. Secondary endpoints included measures of ankle tenderness, joint function, swelling, and patient-reported pain intensity and pain relief. RESULTS: A total of 302 patients were randomized and 95.4% completed the study. The mean (SD) change in POM from baseline to day 5 using the 100-mm VAS was - 42.8 mm (19.7 mm) with DDEA 2.32% gel BID and - 43.1 mm (18.1 mm) with DDEA 1.16% gel QID for the per-protocol population. The least squares mean difference (DDEA gel 2.32% - DDEA gel 1.16%) at this timepoint was 1.11 mm (95% CI - 3.00, 5.22; P = 0.595), and the upper limit (5.22 mm) of the 95% CI was less than the noninferiority margin of 13 mm, demonstrating that DDEA 2.32% gel BID was noninferior to DDEA 1.16% gel QID. Similar trends were seen for the secondary efficacy endpoints. There was no significant difference in the incidence of treatment-emergent adverse events or adverse events adjudicated as being treatment related. All treatment-related adverse events were dermatological; one patient discontinued from the DDEA 2.32% gel BID arm due to application-site inflammation. CONCLUSIONS: DDEA 2.32% gel BID offers a convenient alternative to DDEA 1.16% gel QID, with similar pain reduction and relief, anti-inflammatory effects, and tolerability. TRIAL REGISTRATION: NCT04052620.

A Multiparametric Fusion Radiomics Signature Based on Contrast-Enhanced MRI for Predicting Early Recurrence of Hepatocellular Carcinoma.

Objectives: The postoperative early recurrence (ER) rate of hepatocellular carcinoma (HCC) is 50%, and no highly reliable predictive tool has been developed yet. The aim of this study was to develop and validate a predictive model with radiomics analysis based on multiparametric magnetic resonance (MR) images to predict early recurrence of HCC. Methods: In total, 302 patients (training dataset: n = 211; validation dataset: n = 91) with pathologically confirmed HCC who underwent preoperative MR imaging were enrolled in this study. Three-dimensional regions of interest of the entire lesion were accessed by manually drawing along the tumor margins on the multiple sequences of MR images. Least absolute shrinkage and selection operator Cox regression were then applied to select ER-related radiomics features and construct radiomics signatures. Univariate analysis and multivariate Cox regression analysis were used to identify the significant clinico-radiological factors and establish a clinico-radiological model. A predictive model of ER incorporating the fusion radiomics signature and clinico-radiological risk factors was constructed. The diagnostic performance and clinical utility of this model were measured by receiver-operating characteristic (ROC), calibration curve, and decision curve analyses. Results: The fusion radiomics signature consisting of 6 radiomics features achieved good prediction performance (training dataset: AUC = 0.85, validation dataset: AUC = 0.79). The predictive model of ER integrating clinico-radiological risk factors and the fusion radiomics signature improved the prediction efficacy with AUCs of 0.91 and 0.87 in the training and validation datasets, respectively. Furthermore, the nomogram and ER risk stratification system based on the predictive model demonstrated encouraging predictions of the individualized risk of ER and gave three risk groups with low, intermediate, or high risk of ER. Conclusions: The proposed predictive model incorporating clinico-radiological factors and the fusion radiomics signature derived from multiparametric MR images may be an effective tool for the individualized prediction of postoperative ER in patients with HCC.