Perfusion deficit and vessel wall characteristics to predict recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion.

BACKGROUND: To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. METHODS: We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. RESULTS: Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. CONCLUSIONS: Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.

Mitochondrial Sulfenated-Protein-Targeted Covalent Immobilization Boosting Efficient Copper(II) Depletion for Enhanced Cancer Treatment.

Copper plays a vital role in cellular metabolism and oxidative stress regulation. Visualizing and controlling the copper level in mitochondrion have been proven to be promising and efficient strategies for the diagnosis and treatment of triple-negative breast cancer (TNBC). However, developing an advanced probe for simultaneous visualization and depletion of mitochondrial copper remains a huge challenge. Herein, we for the first time report a mitochondria-anchorable, copper-responsive, and depleting probe d-IR-DPA and evaluate its potential for quantitative visualization of intratumoral copper(II) and anti-TNBC in vivo. Taking advantage of the mitochondrion-targeting and sulfenated-protein-mediated covalent immobilization characteristics, this probe not only enables the quantitative detection of Cu2+ levels in various types of tumors through ratiometric photoacoustic (PA680 nm/PA800 nm) imaging but also scavenges the mitochondrial Cu2+, simultaneously igniting increased oxidative stress and mitochondrial membrane damage and eventually leading to severe TNBC cell apoptosis. More notably, the depletion of Cu2+ by d-IR-DPA can alter the cellular metabolic pathway from oxidative phosphorylation to glycolysis, inducing energy deprivation and significant suppression of TNBC tumor in living mice. Our probe may provide a valuable and powerful means for the effective treatment of TNBC as well as other copper-associated diseases.

The prognostic impact of malnutrition on the outcomes of patients with vertebrobasilar artery occlusion following endovascular treatment.

BACKGROUND AND PURPOSE: Malnutrition is associated with poor outcomes in different diseases. Our aim was to investigate whether measures of malnutrition could be used to predict 90-day outcomes in patients with vertebrobasilar artery occlusion (VBAO) undergoing endovascular treatment (EVT). METHODS: We retrospectively analyzed patients with VBAO who received EVT at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0-3 measured at 90 days. RESULTS: A total of 285 patients were enrolled, of which 260 (91.22 %) met the requirements. According to the CONUT, GNRI, and PNI scores, the proportions of patients classified as moderately or severely malnourished were 7.3 %, 3.08 %, and 35 %, respectively. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of poor prognosis for CONUT scores (adjusted odds ratio [OR]14.91, 95 %CI, 1.69 - 131.71; P = 0.015), GNRI scores (adjusted [OR] 10.67, 1.17 - 96.93; P = 0.036) and PNI scores (adjusted [OR] 4.61, 2.28 - 9.31; P < 0.001). Similar results were obtained when malnutrition scores were analyzed as continuous variables. Adding the 3 malnutrition measures to the risk reclassification that included traditional risk factors significantly improved the predictive value of 3-month poor prognosis. CONCLUSIONS: Our study showed that malnutrition may be associated with poor prognosis within 3 months of EVT in patients with VBAO.

Transjugular intrahepatic portosystemic shunt combined with dual-access thrombolysis for acute severe non-cirrhotic portal-mesenteric vein thrombosis.

OBJECTIVE: Non-cirrhotic porto-mesenteric vein thrombosis (NC-PMVT) is a rare but severe clinical condition. The study aims to assess the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) coupled with dual-access thrombolysis in patients with acute severe NC-PMVT. METHODS: From January 2018 to February 2023, a total of 25 patients with acute severe NC-PMVT who were treated with TIPS in conjunction with mechanical thrombectomy and dual-access thrombolysis. The period of thrombolysis was determined by the improvement of clinical symptoms and vascular recanalization. The technical success, recanalization rate, clinical success, and procedure-related complications were analyzed. RESULTS: The technical success rate was 100 %. The median duration for thrombolytic catheter removal was 5 (IQR 3.5 - 7) days. Full and partial recanalization were accomplished in 10 (40 %) and 15 (60 %) patients respectively before discharge. No significant procedure-related complications were reported. The clinical success rate was 88 %, with a mortality rate of 12 %. Over a median follow-up of 8 months, 3/22 (13.64 %) patients had a recurrence of thrombosis; 1/22 (4.54 %) patients underwent partial intestinal resection one and a half months post-discharge; the remaining patients did not experience any portal hypertensive complications. CONCLUSION: The combination of TIPS and dual-access thrombolysis appears to be safe and effective for patients with acute severe NC-PMVT.

Thrombectomy Alone or Alongside Intravenous Thrombolysis in Managing Acute Ischemic Stroke Caused by Basilar Artery Occlusion: A Multicenter Observational Study.

BACKGROUND AND PURPOSE: It remains unclear whether the combination of endovascular treatment (EVT) with intravenous thrombolysis (IVT) results in a more favorable functional outcome than EVT alone in managing cases of acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO). Thus, this study aimed to compare the outcomes of two approaches-direct EVT (DEVT) and bridging therapy (IVT plus EVT)-in acute BAO patients presenting within 4.5 hours of stroke onset. MATERIALS AND METHODS: This multicenter retrospective cohort study included 153 acute BAO patients presenting within 4.5 hours of stroke onset. Of these patients, 65 (42.5%) and 88 (57.5%) underwent DEVT and bridging therapy, respectively. The primary outcome was defined as good functional outcome (modified Rankin Scale, 0-3) at 90 days. Additionally, pre-operative clinical features, thrombectomy attempts, successful reperfusion rates, incidences of symptomatic intracranial hemorrhage (sICH), and mortality were compared between the two groups. RESULTS: At 90 days, the rate of good functional outcome was comparable between the DEVT (44.6%) and bridging-therapy (39.8%) groups (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 0.55-2.31; p = 0.753). The bridging-therapy group exhibited a lower percentage of patients requiring ≥ 3 attempts of stent retrieval (aOR, 0.39; 95% CI, 0.16-0.93; p = 0.034). Pre-operative clinical features, rate of successful reperfusion, sICH, and mortality were similar between the two groups. CONCLUSIONS: In patients with BAO-induced AIS, DEVT demonstrates a comparable functional outcome to bridging therapy within 4.5 hours of symptom onset, but IVT reduces the number of thrombectomy attempts. ABBREVIATIONS: AIS, acute ischemic stroke; LVO, large-vessel occlusion; EVT, endovascular treatment; IVT, intravenous thrombolysis; BAO, basilar artery occlusion; DEVT, direct endovascular treatment; sICH, symptomatic intracranial hemorrhage; RCT, randomized controlled trial; IRIS, Improving Reperfusion Strategies in Ischemic Stroke; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; mTICI, modified thrombolysis in cerebral infarction; SD, standard deviation; IQR, interquartile range; ICAS, intracranial atherosclerotic stenosis.

Spatial and temporal heterogeneity of soil salinity and ionic coupling relationship under the water-saving renovation of a typical irrigation district in arid and semi-arid areas.

Soil salinization is a global environmental problem. To investigate the spatiotemporal heterogeneity of soil salinity and the coupling relationship of soil salinity ions under water-saving renovation conditions, we chose Shenwu Irrigation Area, where water-saving renovation projects are being conducted comprehensively. Specifically, for our field experiments, we chose 46 soil sampling points. Specifically, we used different spatial interpolation methods and coupling coordination models were applied to study the spatial and temporal distribution of soil salinity and soil salt-based ion coupling relationship changes during different water-saving periods in the irrigation area between 2015 and 2022. The results showed that (1) the emergence of soil salinity extremes after water-saving renovation project led to an increase in the variability of soil salinity. (2) Compared with the Inverse Distance Weighted, Radial Basis Function, and Universal Kriging interpolations, the Mean Absolute Error of the Ordinary Kriging interpolation was reduced by 12.68 %, 43.96 %, and 38.77 %, the Root Mean Square Error was reduced by 14.34 %, 60.85 %, and 36.53 %, reflective of a significant improvement in accuracy, and thus confirming this method to be optimal for elucidating soil salinity. (3) Compared with pre-water-saving renovation project, the average soil desalination rates in the 0-50 cm soil layer during and after project implementation were 5.71 % and 35.67 %. The impact of the water-saving renovation project was highest in channelside areas, followed by croplands, and lowest in lakeside areas. (4) The growth rates of soil salt-based ion coupling degree and coupling coordination degree after project implementation, compared with before implementation, were 17.07 % and 10.81 %. The implementation of water-saving renovation project improved soil quality. This study provides scientific support for the prevention and control of soil salinization in irrigation areas.

S-Sulfenylation Driven Antigen Capture Boosted by Radiation for Enhanced Cancer Immunotherapy.

Radiotherapy (RT)-induced in situ vaccination greatly promotes the development of personalized cancer vaccines owing to the massive release of antigens initiated by tumor-localized RT eliciting the tumor-specific immune response. However, its broad application in cancer treatment is seriously impeded by poor antigen cross-presentation, low response rate, and short duration of efficacy. Herein, the tumor-antigen-capturing nanosystem dAuNPs@CpG consisting of gold nanoparticles, 3,5-cyclohexanedione (CHD), and immunoadjuvant CpG were fabricated to enhance RT-induced vaccination. Taking advantage of the specific covalent binding between CHD and sulfenic acids of antigen proteins, we show that this nanoplatform has an unexpected potential to capture the sulfenylated tumor-derived protein antigens (TDPAs) induced by RT to in situ generate a vaccination effect, achieving significant growth suppression of both primary and distant tumors in combination with PD-1 blockade. We thus believe that our work presents a powerful and effective means to improve the synergistic tumor radioimmunotherapy.

Endovascular treatment for basilar artery occlusion: whether the "weekend effect" affects time metrics and clinical outcomes at a comprehensive stroke center.

Objectives: This study aimed to evaluate whether the "weekend effect" would affect the time metrics and the prognosis of acute ischemic stroke (AIS) patients who underwent endovascular treatment (EVT) due to basilar artery occlusion (BAO). Methods: Clinical data of AIS patients who underwent EVT due to BAO between December 2019 and July 2023 were retrospectively analyzed. At the time when the patients were admitted, the study population was divided into the weekdays daytime group and weekends nighttime group. In the subgroup analysis, the study cohort was divided into four groups: the weekdays daytime group, weekdays nighttime group, weekend daytime group, and weekend nighttime group. A good outcome was defined as a modified Rankin Scale score of ≤3 at 90 days after EVT. Time metrics [e.g. onset-to-door time (ODT) and door-to-puncture time (DPT)] and clinical outcomes were compared using appropriate statistical methods. Results: A total of 111 patients (88 male patients, mean age, 67.7 ± 11.7 years) were included. Of these, 37 patients were treated during weekdays daytime, while 74 patients were treated during nights or weekends. There were no statistically significant differences in ODT (P = 0.136), DPT (P = 0.931), and also clinical outcomes (P = 0.826) between the two groups. Similarly, we found no significant differences in the time metrics and clinical outcomes among the four sub-groups (all P > 0.05). Conclusion: This study did not reveal any influence of the "weekend effect" on the time metrics and clinical outcomes in AIS patients who underwent EVT due to BAO at a comprehensive stroke center.

Comparing Transbrachial and Transradial as Alternatives to Transfemoral Access for Large-Bore Neuro Stenting: Insights From a Propensity-Matched Study.

RATIONALE AND OBJECTIVES: This study aimed to evaluate the safety and effectiveness of transbrachial access (TBA) and transradial access (TRA) compared to transfemoral access (TFA) for large-bore neuro stenting (≥7 F). METHODS: From January 2019 to January 2024, 4752 patients received large-bore neuro stenting in our center. The primary outcomes were procedural metrics. Safety outcomes were significant access site complications, including substantial hematoma, pseudoaneurysm, artery occlusion, and complications requiring treatment (medicine, intervention, or surgery). After propensity score matching with a ratio of 1:1:2 (TBA: TRA: TFA), adjusting for age, gender, aortic arch type, and neuro stenting as covariates, outcomes were compared between groups. RESULTS: 46 TBA, 46 TRA and 92 TFA patients were enrolled. The mean age was 67.8 ± 11.2 years, comprising 127 (69.0%) carotid artery stenting and 57 (31.0%) vertebral artery stenting. The rates of technical success (TBA: 100%, TRA: 95.7%, TFA: 100%) and significant access site complications (TBA: 4.3%, TRA: 6.5%, TFA: 1.1%) were comparable between the groups (P > 0.05). Compared to TFA, the TRA cohort exhibited significant delays in angiosuite arrival to puncture time (14 vs. 8 min, P = 0.039), puncture to angiography completion time (19 vs. 11 min, P = 0.027), and procedural duration (42 vs. 29 min, P = 0.031). There were no substantial differences in procedural time metrics between TBA (10, 14, and 31 min, respectively) and TFA. CONCLUSION: TBA and TRA as the primary access for large-bore neuro stenting are safe and effective. Procedural delays in TRA may favor TBA as the first-line alternative access to TFA.

A transformable and self-oxygenated smart probe for enhanced tumor sonodynamic therapy.

Sonodynamic therapy (SDT) is emerging as a promising modality for cancer treatment. However, improving the tumor bioavailability and anti-hypoxia capability of sonosensitizers faces a big challenge. In this work, we present a tumor microenvironment (TME)-mediated nanomorphology transformation and oxygen (O2) self-production strategy to enhance the sonodynamic therapeutic efficacy of tumors. A smart probe Ce6-Leu@Mn2+ that consists of a glutathione (GSH) and leucine amino peptidase (LAP) dual-responsive unit, a 2-cyanobenzothiazole (CBT) group, and a Mn2+-chelated Ce6 as sonosensitizer for tumor SDT was synthesized, and its SDT potential for liver tumor HepG2 in living mice was systematically studied. It was found that the probes could self-assemble into large nanoparticles in physiological condition and spontaneously transformed into small particles under the dual stimulation of GSH and LAP in TME resulting in enhanced tumor accumulation and deep penetration. More notably, Ce6-Leu@Mn2+ could convert endogenous hydrogen peroxide to O2, thereby alleviating the hypoxia and achieving effective SDT against hypoxic tumors under the excitation of ultrasound. We thus believe this smart TME-responsive probe may provide a noninvasive and efficient means for malignant tumor treatment. STATEMENT OF SIGNIFICANCE: Sonodynamic therapy (SDT) is emerging as a promising therapeutic modality for cancer treatment. However, how to improve the tumor bioavailability and anti-hypoxia capability of sonosensitizers remains a huge challenge. Herein, we rationally developed a theranostic probe Ce6-Leu@Mn2+ that can transform into small-size nanoparticles from initial large particles under the dual stimulation of LAP and GSH in tumor microenvironment (TME) resulting in enhanced tumor accumulation, deep tissue penetration as well as remarkable O2 self-production for enhanced sonodynamic therapy of human liver HepG2 tumor in living mice. This smart TME-responsive probe may provide a noninvasive and efficient means for hypoxic tumor treatment.

Fe-doped Cu-based bimetallic metal-organic frameworks as nanoscale microwave sensitizers for enhancing microwave thermal and dynamic therapy for hepatocellular carcinoma.

Microwave ablation (MWA) is recognized as a novel treatment modality that can kill tumor cells by heating the ions and polar molecules in these cells through high-speed rotation and friction. However, the size and location of the tumor affect the effective ablation range of microwave hyperthermia, resulting in residual tumor tissue and a high recurrence rate. Due to their tunable porous structure and high specific surface area, metal-organic frameworks (MOFs) can serve as microwave sensitizers, promoting microwave energy conversion owing to ion collisions in the porous structure of the MOFs. Moreover, iron-based compounds are known to possess peroxidase-like catalytic activity. Therefore, Fe-doped Cu bimetallic MOFs (FCMs) were prepared through a hydrothermal process. These FCM nanoparticles not only increased the efficiency of microwave-thermal energy conversion as microwave sensitizers but also promoted the generation of reactive oxygen species (ROS) by consuming glutathione (GSH) and promoted the Fenton reaction to enhance microwave dynamic therapy (MDT). The in vitro and in vivo results showed that the combination of MWA and MDT treatment effectively destroyed tumor tissues via microwave irradiation without inducing significant side effects on normal tissues. This study provides a new approach for the combined application of MOFs and microwave ablation, demonstrating excellent potential for future applications.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors Versus Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma with First- or Lower-Order Portal Vein Tumor Thrombosis.

PURPOSE: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). CONCLUSION: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.

Effects of Preoperative Oral Carbohydrate on Perioperative Maternal Outcomes Undergoing Cesarean Section: A Systematic Review and Meta-Analysis.

Purpose: Preoperative oral carbohydrate (CHO) is a rapid postoperative rehabilitation protocol that improves perioperative outcomes and is widely used in adult surgical patients. However, pregnant women are excluded because of the possibility of aspiration due to delayed gastric emptying. This meta-analysis was conducted to evaluate the efficacy of preoperative oral CHO in elective cesarean section. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to July 2023. Randomized controlled trials were included. The risk of bias was assessed using the Cochrane tool. Risk ratios and 95% confidence intervals were calculated. Meta-analysis was performed using random-effects models to estimate risk ratios and mean differences (MDs) with 95% confidence intervals (CIs). The outcomes included thirst and hunger scores, incidence of vomiting and nausea, time to flatus, and homeostatic model assessment of insulin resistance (HOMA-IR). Results: A total of nine studies with 1211 patients were included in the analysis. The levels of thirst and hunger were evaluated using a 10-point visual analog scale, with 0 representing the best and 10 representing the worst. The severity of hunger (weighted mean difference (WMD: -2.34, 95% CI: -3.13 to -1.54), time to flatus (WMD: -3.51 hours, 95% CI: -6.85 to -0.17), and HOMA-IR (WMD: -1.04, 95% CI: -1.31 to -0.77) were significantly lower in the CHO group compared to the control group. However, there were no significant differences in the severity of thirst or the incidence of vomiting and nausea between the CHO and control groups. Conclusion: Preoperative oral CHO during cesarean section alleviates thirst and hunger, shortens the time of postoperative flatus, and reduces HOMA-IR. However, the available evidence is insufficient to reach a clear consensus on the benefits or harms of preoperative oral CHO during cesarean section. Therefore, it is premature to make a definitive recommendation for or against its routine use.

PROTAC-mediated degradation of HIV-1 Nef efficiently restores cell-surface CD4 and MHC-I expression and blocks HIV-1 replication.

The HIV-1 Nef accessory factor enhances the viral life cycle in vivo, promotes immune escape of HIV-infected cells, and represents an attractive antiretroviral drug target. However, Nef lacks enzymatic activity and an active site, complicating traditional occupancy-based drug development. Here we describe the development of proteolysis targeting chimeras (PROTACs) for the targeted degradation of Nef. Nef-binding compounds, based on an existing hydroxypyrazole core, were coupled to ligands for ubiquitin E3 ligases via flexible linkers. The resulting bivalent PROTACs induced formation of a ternary complex between Nef and the cereblon E3 ubiquitin ligase thalidomide-binding domain in vitro and triggered Nef degradation in a T cell expression system. Nef-directed PROTACs efficiently rescued Nef-mediated MHC-I and CD4 downregulation in T cells and suppressed HIV-1 replication in donor PBMCs. Targeted degradation is anticipated to reverse all HIV-1 Nef functions and may help restore adaptive immune responses against HIV-1 reservoir cells in vivo.

Efficacy and Safety of TACE Combined with a Tyrosine Kinase Inhibitor for the Treatment of TACE-Refractory Hepatocellular Carcinoma: A Retrospective Comparative Study.

PURPOSE: Combining angiogenesis inhibitors may enhance therapeutic efficacy synergistically after TACE refractoriness. The purpose of this study was to compare the outcomes of transarterial chemoembolization (TACE) plus a tyrosine kinase inhibitor (TACE-TKI) with TKI only for patients with TACE-refractory hepatocellular carcinoma (HCC). METHODS: From January 2019 to March 2022, 101 HCC patients confirmed with TACE-refractory were retrospectively reviewed in the study. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were evaluated between groups. RESULTS: Fifty-two patients undergoing TACE-TKI, while 32 patients receiving TKI alone were included. The objective response rate (ORR) was higher in the TACE-TKI group compared with the TKI group (55.8% vs. 25.0%, P = 0.006). The median PFS in the TACE-TKI group was significantly longer than that in the TKI group (7.6 months vs. 4.9 months, P = 0.018). The median OS was non reach to statistical longer than that in the TKI alone group (19.5 months vs. 17.7 months, P = 0.055). Subgroup analysis showed that TACE-TKI treatment resulted in a significantly longer median PFS and OS for Barcelona Clinic Liver Cancer (BCLC) stage B patients (PFS 11.8 months vs. 5.1 months, P = 0.017; OS 30.3 months vs. 19.4 months, P = 0.022). CONCLUSION: For patients with TACE-refractory HCC, TACE-TKI appeared to be superior to TKI monotherapy with regard to tumor control and PFS. Furthermore, for the BCLC stage B subgroup, TACE-TKI therapy was superior to TKI monotherapy in both OS and PFS.

Technical Risk Stratification Nomogram Model for 90-Day Mortality Prediction in Patients With Acute Basilar Artery Occlusion Undergoing Endovascular Thrombectomy: A Multicenter Cohort Study.

BACKGROUND: This study aimed to establish and validate a nomogram model for predicting 90-day mortality in patients with acute basilar artery occlusion receiving endovascular thrombectomy. METHODS AND RESULTS: A total of 242 patients with basilar artery occlusion undergoing endovascular thrombectomy were enrolled in our study, in which 172 patients from 3 stroke centers were assigned to the training cohort, and 70 patients from another center were assigned to the validation cohort. Univariate and multivariate logistic regression analyses were adopted to screen prognostic predictors, and those with significance were subjected to establish a nomogram model in the training cohort. The discriminative accuracy, calibration, and clinical usefulness of the nomogram model was verified in the internal and external cohorts. Six variables, including age, baseline National Institutes of Health Stroke Scale score, Posterior Circulation-Alberta Stroke Program Early CT (Computed Tomography) score, Basilar Artery on Computed Tomography Angiography score, recanalization failure, and symptomatic intracranial hemorrhage, were identified as independent predictors of 90-day mortality of patients with basilar artery occlusion and were subjected to develop a nomogram model. The nomogram model exhibited good discrimination, calibration, and clinical usefulness in both the internal and the external cohorts. Additionally, patients were divided into low-, moderate-, and high-risk groups based on the risk-stratified nomogram model. CONCLUSIONS: Our study proposed a novel nomogram model that could effectively predict 90-day mortality of patients with basilar artery occlusion after endovascular thrombectomy and stratify patients with high, moderate, or low risk, which has a potential to facilitate prognostic judgment and clinical management of stroke.

TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.

Stimuli-triggered Self-Assembly of Gold Nanoparticles: Recent Advances in Fabrication and Biomedical Applications.

Gold nanoparticles have been widely used in engineering, material chemistry, and biomedical applications owing to their ease of synthesis and functionalization, localized surface plasmon resonance (LSPR), great chemical stability, excellent biocompatibility, tunable optical and electronic property. In recent years, the decoration and modification of gold nanoparticles with small molecules, ligands, surfactants, peptides, DNA/RNA, and proteins have been systematically studied. In this review, we summarize the recent approaches on stimuli-triggered self-assembly of gold nanoparticles and introduce the breakthrough of gold nanoparticles in disease diagnosis and treatment. Finally, we discuss the current challenge and future prospective of stimuli-responsive gold nanoparticles for biomedical applications.