Clinical predictive value of the age, creatinine, and ejection fraction score in patients in acute type A aortic dissection after total arch replacement.

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34-4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82-6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work.

Impact of peripheral anterior synechiae on the outcome of combined phacoemulsification, goniosynechialysis and goniotomy for primary angle-closure glaucoma and cataract: a multicenter observational study.

PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle-closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataract who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into three groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mmHg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred and four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery (P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the three groups (P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared to 180°≤PAS<270° (P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataract over one year period. However, the outcome was not correlated with preoperative extent of PAS. PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle-closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae.

Opportunistic prediction of osteoporosis in patients with degenerative lumbar diseases: a simplified T12 vertebral bone quality approach.

BACKGROUND: Osteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases. METHODS: We retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis. RESULTS: Total of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18. CONCLUSION: T12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation. TRIAL REGISTRATION: retrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.

Balanced Mass Transfer and Active Sites Density in Hierarchical Porous Catalytic Metal-Organic Framework for Enhancing Redox Reaction in Lithium-Sulfur Batteries.

Developing highly efficient catalysts, characterized by controllable pore architecture and effective utilization of active sites, is paramount in addressing the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs), which, however, remains a formidable challenge. In this study, a hierarchical porous catalytic metal-organic framework (HPC-MOF) with both appropriate porosity and abundant exposed catalytic sites is achieved through time-controlled precise pore engineering. It is revealed that the evolution of the porous structure and catalytic site density is time-dependent during the etching processes. The moderately etched HPC-MOF-M attains heterogeneous pores at various scales, where large apertures ensure fast mass transfer and micropores inherit high-density catalytic sites, enhancing utilization and catalytic kinetics at internal catalytic sites. Capitalizing on these advantages, LSB incorporating the HPC-MOF-M interlayer demonstrates a 164.6% improvement in discharge capability and an 83.3% lower decay rate over long-term cycling at 1.0C. Even under high sulfur loading of 7.1 mg cm-2 and lean electrolyte conditions, the LSB exhibits stable cycling for over 100 cycles. This work highlights the significance of balancing the relationship between mass transfer and catalytic sites through precise chemical regulation of the porous structure in catalytic MOFs, which are anticipated to inspire the development of advanced catalysts for LSBs.

Effect of ethylene production by four pathogenic fungi on the postharvest diseases of green pepper (Capsicum annuum L.).

Ethylene produced by plants generally induces ripening and promotes decay, whereas the effect of ethylene produced by pathogens on plant diseases remains unclear. In this study, four ethylene-producing fungi including Alternaria alternata (A. alternata, Aa), Fusarium verticilliodes (F. verticillioides, Fv), Fusarium fujikuroi 1 (F. fujikuroi 1, Ff-1) and Fusarium fujikuroi 2 (F. fujikuroi 2, Ff-2) were severally inoculated in potato dextrose broth (PDB) media and postharvest green peppers, the ethylene production rates, disease indexes and chlorophyll fluorescence parameters were determined. The results showed that Ff-2 and Fv in the PDB media had the highest and almost the same ethylene production rates. After inoculation with green peppers, Ff-2 treated group still exhibited the highest ethylene production rate, whereas Aa treated group had a weak promotion effect on ethylene production. Moreover, the ethylene production rate of green peppers with mechanical injury was twice that without mechanical injury, and the ethylene production rates of green peppers treated with Aa, Ff-1, Ff-2 and Fv were 1.2, 2.6, 3.8 and 2.8 folds than those of green peppers without treatment, respectively. These results indicated that pathogen infection stimulated the synthesis of ethylene in green peppers. Correlation analysis indicated that the degreening of Fusarium-infected green pepper was significantly positively correlated with the ethylene production rate of green pepper, whereas the disease spot of Aa-infected green pepper had a significant positive correlations with the ethylene production rate of green peppers. Chlorophyll fluorescence results showed that the green peppers already suffered from severe disease after being infected with fungi for 4 days, and Fusarium infection caused early and serious stress, while the harm caused by A. alternata was relatively mild at the early stage. Our results clearly showed that α-keto-γ-methylthiobutyric acid (KMBA)-mediated ethylene synthesis was the major ethylene synthesis pathway in the four postharvest pathogenic fungi. All the results obtained suggested that ethylene might be the main infection factor of Fusarium spp. in green peppers. For pathogenic fungi, stimulating green peppers to produce high level of ethylene played a key role in the degreening of green peppers.

Surgical management of the aortic root in acute type A aortic dissection: A comparative analysis.

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

Pseudo-nanostructure and trapped-hole release induce high thermoelectric performance in PbTe.

Thermoelectric materials can realize direct and mutual conversion between electricity and heat. However, developing a strategy to improve high thermoelectric performance is challenging because of strongly entangled electrical and thermal transport properties. We demonstrate a case in which both pseudo-nanostructures of vacancy clusters and dynamic charge-carrier regulation of trapped-hole release have been achieved in p-type lead telluride-based materials, enabling the simultaneous regulations of phonon and charge carrier transports. We realized a peak zT value up to 2.8 at 850 kelvin and an average zT value of 1.65 at 300 to 850 kelvin. We also achieved an energy conversion efficiency of ~15.5% at a temperature difference of 554 kelvin in a segmented module. Our demonstration shows promise for mid-temperature thermoelectrics across a range of different applications.

Guest Acceptors with Lower Electrostatic Potential in Ternary Organic Solar Cells for Minimizing Voltage Losses.

The ternary strategy, in which one guest component is introduced into one host binary system, is considered to be one of the most effective ways to realize high-efficiency organic solar cells (OSCs). To date, there is no efficient method to predict the effectiveness of guest components in ternary OSCs. Herein, three guest compositions (i.e., ANF-1, ANF-2 and ANF-3) with different electrostatic potential (ESP) are designed and synthesized by modulating the electron-withdrawing ability of the terminal groups through density functional theory simulations. The effects of the introduction of guest component into the host system (D18:N3) on the photovoltaic properties are investigated. The theoretical and experimental studies provide a key rule for guest acceptor in ternary OSCs to improve the open-circuit voltage, that is, the larger ESP difference between the guest and host acceptor, the stronger the intermolecular interactions and the higher the miscibility, which improves the luminescent efficiency of the blend film and the electroluminescence quantum yield (EQEEL) of the device by reducing the aggregation-caused-quenching, thereby effectively decreasing the non-radiative voltage loss of ternary OSCs. This work will greatly contribute to the development of highly efficient guest components, thereby promoting the rapid breakthrough of the 20% efficiency bottleneck for single-junction OSCs.

Second malignant neoplasms within 5 years from first primary diagnosis in pediatric oncology patients in Canada: a population-based retrospective cohort study.

Introduction: From the advancement of treatment of pediatric cancer diagnosis, the five-year survival rate has increased significantly. However, the adverse consequence of improved survival rate is the second malignant neoplasm. Although previous studies provided information on the incidence and risk of SMN in long term survivors of childhood cancer, there is still scarce information known for short term (< 5 years) prognosis. This study aims to assess the incidence, characteristics, management, and outcome of children who develop SMN malignancies within 5 years of diagnosis of their initial cancer. Method: This is a retrospective cohort study of early Second Malignant Neoplasms (SMN) in pediatric oncology patients. The Cancer in Young People - Canada (CYP-C) national pediatric cancer registry was used and reviewed pediatric patients diagnosed with their first cancer from 2000-2015. Results: A total of 20,272 pediatric patients with a diagnosis of a first malignancy were analyzed. Of them, 0.7% were diagnosed with a SMN within the first 5 years following their first cancer diagnosis. Development of a SMN impacted survival, shown by an inferior survival rate in the SMN cohort (79.1%) after three years compared to that of the non-SMN cohort (89.7%). Several possible risk factors have been identified in the study including the use of epipodophyllotoxins, exposure to radiation, and hematopoietic stem cell 169 transplant. Discussion: This is the first national study assessing the incidence, 170 characteristics, risk factors and outcome of early SMN in Canadian children 171 from age 0-15 from 2000-2015.

Rare-Earth Metal-Organic Framework with Nonplanar Porphyrin Groups for High-Efficiency Photocatalysis.

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

Synthesis of Metal-Nitrogen-Carbon Electrocatalysts with Atomically Regulated Nitrogen-Doped Polycyclic Aromatic Hydrocarbons.

Tuning the active site structure of metal-nitrogen-carbon electrocatalysts has recently attracted increasing interest. Herein, we report a bottom-up synthesis strategy in which atomically regulated N-doped polycyclic aromatic hydrocarbons (N-PAHs) of NxC42-x (x = 1, 2, 3, 4) were used as ligands to allow tuning of the active site's structures of M-Nx and establish correlations between the structures and electrocatalytic properties. Based on the synthesis process, detailed characterization, and DFT calculation results, active structures of Nx-Fe1-Nx in Fe1-Nx/RGO catalysts were constructed. The results demonstrated that the extra uncoordinated N atoms around the Fe1-N4 moieties disrupted the π-conjugated NxC42-x ligands, which led to more localized electronic state in the Fe1-N4 moieties and superior catalytic performance. Especially, the Fe1-N4/RGO exhibited optimized performance for ORR with E1/2 increasing by 80 mV and Jk at 0.85 V improved 18 times (compared with Fe1-N1/RGO). This synthesis strategy utilizing N-PAHs holds significant promise for enhancing the controllability of metal-nitrogen-carbon electrocatalyst preparation.

A Study on Interobserver and Intraobserver Reliability of the Huashan Radiologic Classification System for Cervical Spinal Cord Injury Without Fracture and Dislocation.

STUDY DESIGN: Observational study. OBJECTIVE: To assess the reproducibility and reliability of the system. BACKGROUND: The Huashan radiologic classification system for cervical spinal cord injury without fracture and dislocation (CSCIWFD) was recently proposed and found useful for clinical practice. PATIENTS AND METHODS: Patients diagnosed with CSCIWFD between 2015 and 2021 were recruited. Six spine surgeons from different institutions, three experienced and other inexperienced respectively, were trained as observers of the system, and these surgeons classified the recruited patients using the system. Then, 8 weeks later, they repeated the classification on the same patients in a different order. The interobserver and intraobserver agreement between the results was analyzed using percentage agreement, weighted kappa, and Cohen kappa (κ) statistics. RESULTS: A total of 60 patients were included in the analysis. Type I was the most frequent type (29 cases, 48.3%), followed by type II (13 cases, 21.7%), type III (12 cases, 20%), and type IV (6 cases, 10%). For all the observers, experienced observers, and inexperienced observers, the overall agreement percentages were 77.6% (κ = 0.78), 84.4% (κ = 0.84), and 72.8% (κ = 0.74), respectively, indicating substantial to nearly perfect interobserver reproducibility. A higher level of agreement was found for differentiating type I from other types, with the percentage agreement ranging from 87.8% to 94.4% (κ= 0.74-0.88). For distinguishing compression on the spinal cord (types I and II vs types III and IV) among the different groups of observers, the percentage agreement was 97.8% (κ = 0.94), indicating nearly perfect reproducibility. As for intraobserver agreement, the percentage agreement ranged from 86.7% to 96.7% (κ = 0.78-0.95), indicating at least substantial reliability. CONCLUSIONS: The Huashan radiologic classification system for CSCIWFD was easy to learn and apply in a clinical environment, showing excellent reproducibility and reliability. Therefore, it would be promising to apply and promote this system for the precise evaluation and personalized treatment strategy.

Selective oxidation of ß-keto ester modulated by the d-band centers in D-A conjugated microporous metallaphotoredox catalysts containing M-salen (MZn, Cu and Co) and triazine monomers.

Photocatalytic selective oxidation plays an important role in developing green chemistry. However, it is challenging to design an efficient photocatalyst for controlling the selectivity of photocatalytic oxidation reaction and exploring its detailed mechanism. Here, we synthesized three conjugated microporous polymers (CMPs) with D-A structures, named M-SATE-CMPs (MZn, Cu and Co), with different d-band centers based on different metal centers, resulting in the discrepancy in adsorption and activation capacities for the reactants, which produces the selectivity of ß-keto esters being catalyzed into α-hydroperoxide ß-keto esters (ROOH) or to α-hydroxyl ß-keto esters (ROH). Density functional theory (DFT) calculations also demonstrate that the adsorption and activation capacities of the metal active centers in M-SATE-CMPs (MZn, Cu and Co) for ROOH are the key factors to influence the photocatalytic selective oxidation of ß-keto ester. This study provides a promising strategy for designing a metallaphotoredox catalyst whose photocatalytic selectivity depends on the d-band center of metal site in the catalyst.

Self-Assembled Molecules with Asymmetric Backbone for Highly Stable Binary Organic Solar Cells with 19.7 % Efficiency.

The hole-transporting material (HTM), poly (3,4-ethylene dioxythiophene) poly(styrene sulfonate) (PEDOT : PSS), is the most widely used material in the realization of high-efficiency organic solar cells (OSCs). However, the stability of PEDOT : PSS-based OSCs is quite poor, arising from its strong acidity and hygroscopicity. In addition, PEDOT : PSS has an absorption in the infrared region and high highest occupied molecular orbital (HOMO) energy level, thus limiting the enhancement of short-circuit current density (Jsc) and open-circuit voltage (Voc), respectively. Herein, two asymmetric self-assembled molecules (SAMs), namely BrCz and BrBACz, were designed and synthesized as HTM in binary OSCs based on the well-known system of PM6 : Y6, PM6 : eC9, PM6 : L8-BO, and D18 : eC9. Compared with BrCz, BrBACz shows larger dipole moment, deeper work function and lower surface energy. Moreover, BrBACz not only enhances photon harvesting in the active layer, but also minimizes voltage losses as well as improves interface charge extraction/ transport. Consequently, the PM6 : eC9-based binary OSC using BrBACz as HTM exhibits a champion efficiency of 19.70 % with a remarkable Jsc of 29.20 mA cm-2 and a Voc of 0.856 V, which is a record efficiency for binary OSCs so far. In addition, the unencapsulated device maintains 95.0 % of its original efficiency after 1,000 hours of storage at air ambient, indicating excellent long-term stability.

Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE).

BACKGROUND: The efficacy of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been established in several trials in people with type 2 diabetes mellitus (T2DM); however, real-world evidence on their effectiveness is limited. This study evaluated the effectiveness of OW GLP-1RA regarding glycemic and weight outcomes, and relative to DPP-4i in a comparator analysis. METHODS: This observational cohort study evaluated glycated hemoglobin (HbA1c) and weight outcomes in people with T2DM with two or more prescription claims for the same OW GLP-1RA using a pre-post study design (including for a semaglutide OW T2DM subgroup, hereafter referred to as semaglutide). Comparator analysis for the same outcome was performed for OW GLP-1RAs versus DPP-4i and semaglutide subgroup versus DPP-4i. A linked patient population from the IQVIA PharMetrics® Plus database and the Ambulatory Electronic Medical Records (AEMR) database was analyzed using data from January 2017 to April 2022. HbA1c and weight were assessed at baseline and at the end of the 12-month post-index period. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline patient characteristics in the comparator analysis. RESULTS: In the pre-post analysis, a greater numerical reduction in HbA1c and weight was observed for the semaglutide subgroup (N = 354) relative to the OW GLP-1RA cohort (N = 921). In the semaglutide subgroup, 52.5% and 34.2% of patients achieved HbA1c of < 7.0% and ≥ 5% weight loss, respectively. For the comparator analysis, the OW GLP-1RAs (N = 651) were significantly more effective (p < 0.001) in reducing HbA1c (- 1.5% vs. -  1.0%) and weight (- 3.2 kg vs. -  1.0 kg) than the DPP-4is (N = 431). Similarly, the semaglutide cohort (N = 251) also displayed more effectiveness (p < 0.001) in reducing HbA1c (- 1.7% vs. -  0.9%) and weight (- 4.1 kg vs. -  1.3 kg) than the respective DPP-4i cohort (N = 417). Patients initiating OW GLP-1RAs, including the semaglutide cohort, were at least twice as likely to achieve HbA1c and weight outcomes as well as composite outcomes compared with those initiating DPP-4is. CONCLUSION: The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world setting. These findings align with the recommendation in the current guidelines for utilizing glucose-lowering treatment regimens that support weight-management goals in people with T2DM.

In type 2 diabetes mellitus (T2DM), glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for managing blood sugar levels and major adverse cardiovascular event risk reduction. In clinical trials, once-weekly (OW) GLP-1RAs showed better control of blood sugar levels and body weight than those administered daily, as well as another class of daily T2DM medications called dipeptidyl peptidase-4 inhibitors (DPP-4is). However, there is limited evidence of OW GLP-1RAs-based routine care to confirm these findings. This study gathered prescription and outcomes data for people with T2DM (January 2017­April 2022) from two linked US databases. Body weight measurements and glycated hemoglobin (HbA_1c) test results (measuring average blood sugar levels) were used to evaluate the effectiveness of OW GLP-1RAs (exenatide, dulaglutide, and semaglutide) via a pre-post analysis, and compare OW GLP-1RAs with DPP-4is. We found that treatment with semaglutide lowered body weight and blood sugar levels to a greater extent than OW GLP-1RAs in the pre-post analysis. In the comparator analysis, people receiving OW GLP-1RAs, including semaglutide, were at least twice as likely to achieve reduced HbA_1c levels and body weight compared with those receiving DPP-4is. People receiving OW GLP-1RAs were three times more likely than those on DPP-4is to achieve the recommended target of HbA_1c < 7.0% and weight loss ≥ 5%, while treatment with semaglutide increased this likelihood by > 4.6 times. This study shows clear benefits of OW GLP-1RAs, building on current evidence for integration of this treatment into overall management of T2DM.

Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy.

Background: Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway. Methods: In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 µM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers. Results: DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells. Conclusions: This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.

Exploring the efficacy and safety of drug-eluting beads transarterial chemoembolization in pancreatic cancer liver metastasis.

OBJECTIVES: Drug-eluting beads transarterial chemoembolization (DEB-TACE) has shown promise as a treatment modality for primary liver cancer and colorectal cancer liver metastasis. However, its role in pancreatic cancer liver metastasis (PCLM) remains uncertain. This study aimed to investigate the efficacy and safety of DEB-TACE in PCLM patients. METHODS: A retrospective study included 10 PCLM patients who underwent DEB-TACE using CalliSpheres® microspheres as the chemoembolization material. Treatment response, survival outcomes, adverse events, and liver function indexes were comprehensively assessed. RESULTS: Among the patients, complete response, partial response, stable disease, and progressive disease rates were 0.0%, 40.0%, 30.0%, and 30.0%, respectively. The objective response rate was 40.0%, and the disease-control rate was 70.0%. The median progression-free survival (PFS) was 12.0 months (95% CI: 0.0-26.7), with a 1-year PFS rate of 48.0%. The median overall survival (OS) was 18.0 months (95% CI: 6.0-30.0), with a 1-year OS rate of 80.0%. Additionally, no significant differences were observed in any of the liver function indexes, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, etc., between pre- and posttreatment evaluations. Adverse events included pain, grade 1-2 vomiting, fever, and transient liver dysfunction. CONCLUSIONS: DEB-TACE demonstrates a promising treatment response, favorable survival profile, and satisfactory safety in PCLM patients. ADVANCES IN KNOWLEDGE: This study adds to the current research by providing novel evidence on the efficacy, safety, and favorable survival outcomes of DEB-TACE in treating PCLM, highlighting its potential as an effective therapeutic option in this specific population.

Bioinformatics analysis and experimental validation of key genes associated with lumbar disc degeneration and biomechanics.

Background: Lumbar disc degeneration (LDD) is an important pathological basis for the development of degenerative diseases of the lumbar spine. Most clinical patients have low back pain as their main symptom. The deterioration of the biomechanical environment is an important cause of LDD. Although there is a large amount of basic research on LDD, there are fewer reports that correlate biomechanical mechanisms with basic research. Our research aims to identify 304 key genes involved in LDD due to biomechanical deterioration, using a bioinformatics approach. We focus on SMAD3, CAV1, SMAD7, TGFB1 as hub genes, and screen for 30 potential target drugs, offering novel insights into LDD pathology and treatment options. Methods: The Gene Cards, GenCLip3, OMIM and Drugbank databases were explored to obtain genes associated with biomechanics and LDD, followed by making veen plots to obtain both co-expressed genes. GO enrichment analysis and KEGG pathway analysis of the co-expressed genes were obtained using the DAVID online platform and visualised via a free online website. Protein interaction networks (PPI) were obtained through the STRING platform and visualised through Cytoscape 3.9.0. These genes were predicted for downstream interaction networks using the STITCH platform. Then, the GSE56081 dataset was used to validate the key genes. RT-PCR was used to detect mRNA expression of core genes in the degenerated nucleus pulposus (NP) samples and western bolt was used for protein expression. Lastly, the obtained hub genes were searched in the drug database (DGIdb) to find relevant drug candidates. Results: From the perspective of biomechanics-induced LDD, we obtained a total of 304 genes, the GO functional enrichment and KEGG pathway enrichment analysis showed that the functions of these genes are mostly related to inflammation and apoptosis. The PPI network was constructed and four Hub genes were obtained through the plug-in of Cytoscape software, namely SMAD3, CAV1, SMAD7 and TGFB1. The analysis of key genes revealed that biomechanical involvement in LDD may be related to the TGF-ß signaling pathway. Validation of the GSE56081 dataset revealed that SMAD3 and TGFB1 were highly expressed in degenerating NP samples. RT-PCR results showed that the mRNA expression of SMAD3 and TGFB1 was significantly increased in the severe degeneration group; Western blot results also showed that the protein expression of TGFB1 and P-SMAD3 was significantly increased. In addition, we identified 30 potential drugs. Conclusion: This study presented a new approach to investigate the correlation between biomechanical mechanisms and LDD. The deterioration of the biomechanical environment may cause LDD through the TGF-ß signaling pathway. TGFB1 and SMAD3 are important core targets. The important genes, pathways and drugs obtained in this study provided a new basis and direction for the study, diagnosis and treatment of LDD.