Inflammation-Targeted Biomimetic Nano-Decoys via Inhibiting the Infiltration of Immune Cells and Effectively Delivering Glucocorticoids for Enhanced Multiple Sclerosis Treatment.

Excessive infiltration of neutrophil and inflammatory cytokines accumulation as well as the inadequate delivery of drugs to the targeted site are key pathological cascades in multiple sclerosis (MS). Herein, inflammation-targeting biomimetic nano-decoys (TFMN) is developed that inhibit the infiltration of immune cells and effectively deliver glucocorticoids to lesions for enhanced MS treatment. Nano-decoys encapsulated with the glucocorticoid methylprednisolone (MPS) are prepared by coating neutrophil membrane (NM) on nanoparticles formed by the self-assembly of tannic acid and poloxamer188/pluronic68. Benefiting from the natural inflammation-targeting ability of activated neutrophil membranes, TFMN can target the lesion site and prevent neutrophils infiltration by adsorbing and neutralizing elevated neutrophil-related cytokines, subsequently modulating the inflammatory microenvironment in experimental autoimmune encephalomyelitis mice. TFMN exhibits a strong antioxidant capacity and scavenged excessive reactive oxygen species to enhance neuronal protection. Furthermore, at the inflammation site, perforin, discharged by cytotoxic T-lymphocytes, triggered the controlled release of MPS within the TFMN through perforin-formed pores in the NM. Simultaneously, this mechanism protected neurons from perforin-induced toxicity. The MPS liberated at the targeted site achieves optimal drug accumulation, thereby enhancing therapeutic efficacy. In conclusion, the innovative system shows potential for integrating various therapeutic agents, offering a novel strategy for CNS disorders.

Microwave versus Radiofrequency Ablation in Treating Predominantly Solid Benign Thyroid Nodules: A Randomized Controlled Trial.

Background Current guidelines recommend radiofrequency ablation (RFA) as the first-line treatment for benign thyroid nodules. Purpose To compare the efficacy and safety of microwave ablation (MWA) and RFA for the treatment of predominantly solid benign thyroid nodules. Materials and Methods This prospective, randomized, open-label, multicenter study was conducted from August 2019 to February 2023. Participants with nonfunctioning, predominantly solid benign thyroid nodules from five institutions were randomly assigned with a 1:1 ratio to receive MWA or RFA treatment. Participants were followed up for at least 2 years. Primary outcomes were 6-month and 2-year volume reduction rate (VRR) of nodules after ablation. Secondary outcomes included VRR change over time, complications, and technique efficacy (defined as volumetric reduction ≥ 50% of the initial nodule volume). Continuous variables and categorical variables were compared using the t test and the χ2 test or Fisher exact test, respectively. Results This study included 76 participants in the MWA group (mean age, 46 years ± 12 [SD]; 58 female participants) and 76 in the RFA group (mean age, 50 years ± 13; 56 female participants). MWA was noninferior to RFA in terms of 6-month (mean difference, -5.6%; P = .01) and 2-year (-2.4%; P < .001) VRR after ablation. Comparing MWA and RFA, no evidence of a difference was observed for VRR change over time (mean difference from mixed-effects analysis, 6.9% [95% CI: -0.5, 13.9]; P = .73) or technique efficacy (91% vs 86%; P = .40). The most common major complication was voice change, which occurred in 6.6% of participants in the MWA group and 1.3% of participants in the RFA group (P = .21). Conclusion MWA and RFA showed comparable efficacy for treating participants with predominantly solid benign thyroid nodules. However, a larger sample size is needed to demonstrate that safety is comparable between the procedures. ClinicalTrials.gov Identifier: NCT04046354 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by McGahan in this issue.

Reclamation alters evapotranspiration and its biophysical controls in a meadow grassland on the Mongolian Plateau.

Global grasslands were constantly being replaced and reclaimed for cropland, and such reclamations may profoundly affect ecological such as water cycles. However, the long-term effects of this conversion on evapotranspiration (ET) processes remain underexplored. To discern changes in ET from grassland to reclaimed cropland and among different crop rotations, a four-year study (2018-2021) was conducted using the eddy covariance system in a Hulunber grassland and a neighboring reclaimed cropland. The ET in reclaimed cropland (248 mm) was 49% higher than the grassland (166 mm) during the growing season (crop growth period), whereas the ET in the grassland (134 mm) exceeded that in the cropland (128 mm) by 6% in the non-growing season. The croplands experienced a 19% increase in precipitation, primarily due to artificial irrigation during the growing season. Meanwhile, the increase in ET in reclaimed cropland might also be influenced by changes in vegetation type and crop growth characteristics, as well as by rational tillage practices that increase the cover of vegetation and biomass. Notably, potato cultivation most closely matched the water balance of grasslands. In addition, irrigation directly increased soil water content (SWC), and that enhancing the sensitivity of ET to SWC. Overall, this study highlighted the importance of understanding ET variations due to grassland conversion to cropland and different crop rotations, emphasizing the role of irrigation and tillage practices.

Image-guided percutaneous microwave ablation for unresectable pancreatic cancers: A multicenter retrospective study.

OBJECTIVE: This study aims to assess the feasibility, effectiveness, and safety of image-guided percutaneous microwave ablation (PMWA) for unresectable pancreatic cancer. METHODS: In this retrospective study, 72 patients from four hospitals were enrolled between November 2009 and October 2022. Descriptive statistics were employed to describe the patients' characteristics and prognostic factors. The primary endpoint compassed the complete ablation rate (CAR), incidence of complications and the pain relief rate (PRR). RESULTS: The median age of the 72 patients was 61 (interquartile range (IQR) 52.5-67.0) years, with 62.5 % (45/72) being male. 26 cases received computed tomography (CT) guidance; 46 cases received ultrasound guidance. A total of 74 tumors were identified (2 in 2 patients), with 56.8 % (42/74) at the body and tail, and the rest at the head and neck. Overall, 73 ablation sessions were carried out, achieving a technical success rate (TSR) of 100 %. The CAR was 40.5 % (30/74). The median follow-up time was 4.6 (1-43.4) months. 50 % (36/72) of patients had died with a median overall survival (OS) of 5.6 (1-27) months. Regarding complications, 18.1 % (13/72) of cases were classified as grade I and II, and 9.8 % (7/72) as grade IIIa. Before surgery, 33 patients experienced pain symptoms, and the postoperative PRR was 96.7 % (32/33). The average pain score decreased from 6.3 (4-10) before surgery to 2.0 (0-8) after ablation (P<0.001). CONCLUSIONS: Image-guided PMWA for unresectable pancreatic cancer is safe and feasible, effectively relieving cancer pain and improving patients' the quality of life.

Modeling and Analysis of Wide Frequency Band Coaxial TSV Transmission Interconnect.

In this paper, we first build the 3D model of coaxial TSV(CTSV), RDL, and bump of the CTSV interconnect, and extract the equivalent circuit model of each part. Then, we get the S-parameters of the 3D and equivalent circuit model of the CTSV interconnect structure; the validity of the equivalent circuit model is verified by comparing the consistency of the S-parameters. The simulation results show that the maximum errors for the S11 and S21 parameters are 0.4% and 0.18%, respectively, which proves the validity of the equivalent circuit modeling in this paper. Finally, parametric analysis is performed to investigate the effect of different model parameters on the signal-transmission characteristics of the CTSV interconnect.

The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body.

Cilia are antenna-like organelles protruding from the surface of many cell types in the human body. Defects in ciliary structure or function often lead to diseases that are collectively called ciliopathies. Cilia and flagella-associated protein 410 (CFAP410) localizes at the basal body of cilia/flagella and plays essential roles in ciliogenesis, neuronal development and DNA damage repair. It remains unknown how its specific basal body location is achieved. Multiple single amino acid mutations in CFAP410 have been identified in patients with various ciliopathies. One of the mutations, L224P, is located in the C-terminal domain (CTD) of human CFAP410 and causes severe spondylometaphyseal dysplasia, axial (SMDAX). However, the molecular mechanism for how the mutation causes the disorder remains unclear. Here, we report our structural studies on the CTD of CFAP410 from three distantly related organisms, Homo sapiens, Trypanosoma brucei and Chlamydomonas reinhardtii. The crystal structures reveal that the three proteins all adopt the same conformation as a tetrameric helical bundle. Our work further demonstrates that the tetrameric assembly of the CTD is essential for the correct localization of CFAP410 in T. brucei, as the L224P mutation that disassembles the tetramer disrupts its basal body localization. Taken together, our studies reveal that the basal body localization of CFAP410 is controlled by the CTD and provide a mechanistic explanation for how the mutation L224P in CFAP410 causes ciliopathies in humans.

Finite immune imprinting on neutralizing antibody responses to Omicron subvariants by repeated vaccinations.

OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

Soil environmental anomalies dominate the responses of net ecosystem productivity to heatwaves in three Mongolian grasslands.

Climate change is causing more frequent and intense heatwaves. Therefore, it is important to understand how heatwaves affect the terrestrial carbon cycle, especially in grasslands, which are especially susceptible to climate extremes. This study assessed the impact of naturally occurring, simultaneous short-term heatwaves on CO2 fluxes in three ecosystems on the Mongolia Plateau: meadow steppe (MDW), typical steppe (TPL), and shrub-grassland (SHB). During three heatwaves, net ecosystem productivity (NEP) was reduced by 86 %, 178 %, and 172 % at MDW, TPL, and SHB, respectively. The changes in ecosystem respiration, gross primary production, evapotranspiration, and water use efficiency were divergent, indicating the mechanisms underlying the observed NEP decreases among the sites. The impact of the heatwave in MDW was mitigated by the high soil water content, which enhanced evapotranspiration and subsequent cooling effects. However, at TPL, insufficient soil water led to combined thermal and drought stress and low resilience. At SHB, the ecosystem's low tolerance to an August heatwave was heavily influenced by species phenology, as it coincided with the key phenological growing phase of plants. The potential key mechanism of divergent NEP response to heatwaves lies in the divergent stability and varying importance of environmental factors, combined with the specific sensitivity of NEP to each factor in ecosystems. Furthermore, our findings suggest that anomalies in soil environment, rather than atmospheric anomalies, are the primary determinants of NEP anomalies during heatwaves. This challenges the conventional understanding of heatwaves as a discrete and ephemeral periods of high air temperatures. Instead, heatwaves should be viewed as chronologically variable, compound, and time-sensitive environmental stressors. The ultimate impact of heatwaves on ecosystems is co-determined by a complex interplay of environmental, biological, and heatwave features.

Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection.

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.

CS/PVP Hydrogel-Based Nanocapillary for Monitoring Bacterial Growth and Rapid Antibiotic Susceptibility Testing.

Infection with drug-resistant bacteria poses a significant threat to human health. Judicious use of antibiotics could reduce the likelihood of bacterial resistance, which can be evaluated through antibiotic susceptibility testing (AST). This paper focuses on the application of a needle-like nanocapillary tip filled with chitosan (CS)/polyethylene pyrrolidone (PVP) hydrogel based on its specific pH-sensitive properties. The gel-filled nanocapillary has the potential to be used for electrical pH detection with a sensitivity of 3.06 nA/pH and a linear range from 7.3 to 4.3. Such sensitivity for pH measurement could be extended for monitoring of bacterial (such as Escherichia coli and Streptococcus salivarius) growth because of the relationship between pH and bacterial growth. Bacterial growth curves obtained using the hydrogel-filled nanocapillary showed good agreement with the OD600 method. Moreover, this device could be applied for rapid AST for tetracycline and norfloxacin on E. coli with minimum inhibitory concentrations of 2 and 0.125 µg/mL, respectively. This study expands the application of the hydrogel-based nanocapillary for bacterial research by monitoring changes in pH values.

Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Causal relationships between gut microbrome and digestive system diseases: A two-sample Mendelian randomization study.

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.

Efficacy of microwave ablation in the treatment of large benign thyroid nodules: a multi-center study.

OBJECTIVE: To evaluate the efficacy, safety, and improvement of symptoms by ultrasound-guided microwave ablation (MWA) for patients with large benign thyroid nodules (BTNs). METHODS: Eighty-seven patients with 87 BTNs (≥ 4 cm) treated with MWA between April 2015 and March 2021 were enrolled in this retrospective multicenter study, with clinical and ultrasound examinations performed at the 1st, 3rd, 6th, and 12th months. A multivariable linear mixed effects model was employed to explore the alterations in volume and volume reduction ratio (VRR), as well as the potential factors associated with VRR. RESULTS: The mean age of the 87 patients was 45.69 ± 14.21 years (range 18-76 years), and the ratio of men to women was 1:4.8. The mean volumes were much decreased at the 12th month after ablation compared to the initial volumes (p < .001). The mean VRR was 76.09% at the 12th month. The technique efficacy (VRR > 50%) was 90.80% at the 12th month. A multivariate analysis revealed that VRR was related to the initial volume (p = .015), annular flow (p = .010), and nodule composition (p = .024). The mean symptomatic score decreased from 4.40 ± 0.28 to 0.26 ± 0.06 at the 12th month (p < .001). At the same time, the mean cosmetic score decreased from 3.22 ± 0.10 to 1.31 ± 0.08 (p < .001). CONCLUSION: MWA could serve as a safe and effective therapy for large BTNs, significantly reducing the volume of BTNs and significantly improving compressive symptoms and appearance problems. CLINICAL RELEVANCE STATEMENT: Microwave ablation could serve as a safe and effective therapy for large benign thyroid nodules, leading to significant volume reduction and satisfied symptom and cosmetic alleviation period. KEY POINTS: • This multicenter study investigated the feasibility and safety of microwave ablation for large benign thyroid nodules. • After ablation, the nodule volume was significantly reduced, and patients' symptoms and appearance problems were significantly improved. • Microwave ablation is feasible for large benign thyroid nodules and has been a supplement treatment.

Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience.

PURPOSE: To investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). MATERIALS AND METHODS: This was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. RESULTS: The technical success rate was 93.5% (29/31). No major adverse events occurred. Local tumor progression occurred after 2 sessions (6.5%, 2/31), and intrahepatic distant metastasis occurred after 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3-117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1-112.8) and 23.8 months (95% CI: 15.4-32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. CONCLUSIONS: Image-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that resulted in local tumor control and a favorable long-term prognosis.

Spatiotemporal patterns and driving factors of gross primary productivity over the Mongolian Plateau steppe in the past 20 years.

The Eurasian steppe is the largest temperate grassland in the world. The grassland of the Mongolian Plateau (MP) represents an important part of the Eurasian steppe with high climatic sensitivity. Gross primary productivity (GPP) is a key indicator of the grassland's production, status and dynamic on the MP. In this study, we calibrated and evaluated the grassland-specific light use efficiency model (GRASS-LUE) against the observed GPP collected from nine eddy covariance flux sites on the MP, and compared the performance with other four GPP products (MOD17, VPM, GLASS and GOSIF). GRASS-LUE with higher R2 (0.91) and lower root mean square error (RMSE = 0.99 gC m-2 day-1) showed a better performance compared to the four GPP products in terms of model accuracy and dynamic consistency, especially in typical and desert steppe. The parameters of the GRASS-LUE are more suitable for water-limited grassland could be the reason for its outstanding performance in typical and desert steppe. Mean grassland GPP derived from GRASS-LUE was higher in the east and lower in the west of the MP. Grassland GPP was on average 205 gC m-2 over the MP between 2001 and 2020 with mean annual total GPP of 322 TgC yr-1. 30 % of the MP steppe showed a significant GPP increase. Growing season precipitation is the main factor affecting GPP of the MP steppe across regions. Anthropogenic factors (livestock density and population density) had greater effect on GPP than growing season temperature in pastoral counties in IM that take grazing as one of main industries. These findings can inform the status and trend of the productivity of MP steppe and help government and scientific research institutions to understand the drivers for spatial pattern of grassland GPP on the MP.

Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop.

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.

Safety and Efficacy of Ultrasound-Guided Radiofrequency Ablation in the Treatment of Gallbladder Polyps.

RATIONALE AND OBJECTIVES: To investigate the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) in the treatment of gallbladder polyps. MATERIALS AND METHODS: A retrospective analysis was conducted on the medical records of 296 patients diagnosed with gallbladder polyps. The study observed the changes in lesions post-procedure within the ablation group, and compared whether there was a difference in the gallbladder contraction rate in patients before and after ablation. It also compared the liver function indicators before and after surgery, some indicators during the periprocedural period, and the incidence of complications in two groups of patients. RESULTS: In the ablation group, all lesions (84/84) were completely ablated, and the absorption effect of the ablation lesions was good after the ablation. No significant differences were observed in the gallbladder contraction rate before ablation compared to 1 month and 3 months post-ablation (p > 0.05). After the operation, statistically significant differences were observed in ALT and TP between the two groups (all p < 0.05). Significant differences were observed between the two groups in terms of hospital stay, procedural time, postprocedural mobilization time, postprocedural exhaust time, postprocedural eating time, and VAS score on postprocedural day 3 (all p < 0.05). There was no significant difference in the incidence of complications between the two groups (x2=0.477，p = 0.490). CONCLUSION: Our findings demonstrate that ultrasound-guided RFA is a safe, effective, and feasible treatment for gallbladder polyps, as it not only effectively eliminates the polyps but also preserves the physiological functions of the gallbladder.

Discovery of (quinazolin-6-yl)benzamide derivatives containing a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety as potent reversal agents against P-glycoprotein-mediated multidrug resistance.

P-glycoprotein (P-gp) is an important factor leading to multidrug resistance (MDR) in cancer treatment. The co-administration of anticancer drugs and P-gp inhibitors has been a treatment strategy to overcome MDR. In recent years, tyrosine kinase inhibitor Lapatinib has been reported to reverse MDR through directly interacting with ABC transporters. In this work, a series of P-gp inhibitors (1-26) was designed and synthesized by integrating the quinazoline core of Lapatinib into the molecule framework of the third-generation P-gp inhibitor Tariquidar. Among them, compound 14 exhibited better MDR reversal activity than Tariquidar. The docking results showed compound 14 displayed the L-shaped molecular conformation. Importantly, compound 14 increased the accumulation of Adriamycin (ADM) and rhodamine 123 (Rh123) in MCF7/ADM cells. Besides, compound 14 significantly increased ADM-induced apoptosis and inhibited the proliferation, migration and invasion of MCF7/ADM cells. It was also demonstrated that compound 14 significantly inhibited the growth of MCF7/ADM xenograft tumors by increasing the sensitivity of ADM. In summary, compound 14 has the potential to overcome MDR caused by P-gp.