CD47-SIRPα Blockade Sensitizes Head and Neck Squamous Cell Carcinoma to Cetuximab by Enhancing Macrophage Adhesion to Cancer Cells.

Developing effective treatments for patients with head and neck squamous cell carcinoma (HNSCC) is a significant challenge. Cetuximab, a first-line targeted therapy for HNSCC, exhibits limited efficacy. Here, we used pooled CRISPR screening to find targets that can synergize with cetuximab and identified CD47 as the leading candidate. Rather than inhibiting cancer cell proliferation, CD47 inhibition promoted cetuximab-triggered antibody-dependent cellular phagocytosis (ADCP), thereby enhancing macrophage-mediated cancer cell removal. The combination of CD47-SIRPα blockade and cetuximab demonstrated strong anticancer activity in vivo. In addition to blocking the phagocytosis checkpoint, CD47-SIRPα inhibition upregulated CD11b/CD18 on the surface of macrophages, which accelerated intercellular adhesion between macrophages and cancer cells to enhance subsequent phagocytosis. Inhibition of the interaction between macrophage CD11b/CD18 and cancer cell ICAM1 eliminated the intercellular adhesion and phagocytosis induced by CD47-SIRPα blockade. Thus, CD47-SIRPα blockade enhances ADCP through CD11b/CD18-ICAM1-mediated intercellular adhesion and sensitizes HNSCC to cetuximab.

Inferior Interfacial Superconductivity in 1 UC FeSe/SrVO3/SrTiO3 with Screened Interfacial Electron-Phonon Coupling.

Single-unit cell (1 UC) FeSe interfaced with TiOx or FeOx exhibits significantly enhanced superconductivity compared to that of bulk FeSe, with interfacial electron-phonon coupling (EPC) playing a crucial role. However, the reduced dimensionality in 1 UC FeSe, which may drive superconducting fluctuations, complicates our understanding of the enhancement mechanisms. We construct a new superconducting interface, 1 UC FeSe/SrVO3/SrTiO3. Here, the itinerant electrons of highly metallic SrVO3 films can screen all high-energy Fuchs-Kliewer phonons, including those of SrTiO3, making it the first FeSe/oxide system with screened interfacial EPC while maintaining the 1 UC FeSe thickness. Despite comparable doping levels, the heavily electron-doped 1 UC FeSe/SrVO3 exhibits a pairing temperature (Tg ∼ 48 K) lower than those of FeSe/SrTiO3 and FeSe/LaFeO3. Our findings disentangle the contributions of interfacial EPC from dimensionality in terms of enhancing Tg in FeSe/oxide interfaces, underscoring the critical importance of interfacial EPC. This FeSe/VOx interface also provides a platform for studying interfacial superconductivity.

Cachexia Index as a Predictor of Reduced Survival in Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

The cachexia index is a novel indicator of cachexia, but its prognostic implications for survival outcomes have not been systematically assessed in patients with gastrointestinal cancer. This systematic review and meta-analysis aimed to examine the association between the cachexia index and survival outcomes in gastrointestinal cancer patients. Two independent reviewers searched PubMed, Embase, and Web of Science to identify studies that evaluated the prognostic significance of the cachexia index in patients with gastrointestinal cancer. The prognostic value of the cachexia index was determined by combining the adjusted hazard ratios (HR) and 95% confidence intervals (CI). Thirteen studies were identified, including a total of 4207 patients. Meta-analysis indicated that a lower cachexia index was associated with shorter overall survival (HR 2.18; 95% CI 1.78-2.66) and disease-free survival (HR 1.72; 95% CI 1.50-1.97) in gastrointestinal cancer patients. Further stratified analysis confirmed the significant association between a lower cachexia index and shorter overall survival in different study designs, regions, patients' age, sample sizes, gastrointestinal cancer subtypes, tumor stages, and follow-up duration subgroups. The cachexia index could be utilized as a predictor of overall survival and disease-free survival in patients with gastrointestinal cancer. However, future prospective studies are required to confirm these findings.

0D/2D heterojunction constructed by Ag2S quantum dots anchored on graphdiyne (g-CnH2n-2) nanosheets for wide spectrum photocatalytic H2 evolution.

Precisely crafting heterojunctions for efficient charge separation is a major obstacle in the realm of photocatalytic hydrogen evolution. A 0D/2D heterojunction was successfully fabricated by anchoring Ag2S quantum dots (Ag2S QDs) onto graphdiyne (GDY) nanosheets (Ag2S QDs/GDY) using a straightforward physical mixing technique. This unique structure allows for excellent contact between GDY and Ag2S QDs, thereby enhancing the rate of charge transfer. The light absorption capabilities of Ag2S QDs/GDY extend up to 1200 nm, enabling strong absorption of light, including infrared. Through DFT calculations and in-situ XPS analysis, it was demonstrated that incorporating Ag2S QDs onto GDY effectively modulates the electronic structure, promotes an internal electric field, and facilitates directional electron transfer. This directed electron transfer enhances the utilization of electrons by GDY and Ag2S QDs, with the added benefit of Ag2S QDs serving as electron reservoirs for efficient photocatalytic hydrogen evolution. A 7 %Ag2S QDs/GDY composite exhibited impressive efficiency and stable performance in photocatalytic hydrogen evolution (2418 µmol g-1 h-1), which is much higher than that of GDY and Ag2S QDs. This study conclusively demonstrates that the 0D/2D heterojunction formed by GDY and Ag2S QDs can establish high-quality contact and efficient charge transfer, ultimately enhancing photocatalytic performance.

Discovery of baicalein derivatives as novel inhibitors against human pancreatic lipase: Structure-activity relationships and inhibitory mechanisms.

Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC50 < 1 µM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (Ki < 1 µM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo.

Physician preferences for nonmetastatic castration-resistant prostate cancer treatment in China.

Introduction: The treatment preferences of Chinese physicians who treat nonmetastatic castration-resistant prostate cancer (nmCRPC) and how they weigh the benefits and risks of nmCRPC treatment are still unknown. This study aimed to evaluate Chinese physicians' benefit-risk treatment preferences for nmCRPC and assist in setting nmCRPC treatment goals. Methods: A paper-based discrete choice experiment (DCE) survey was administered to 80 nmCRPC-treating physicians. DCE responses were analyzed to produce the preference weight and the relative importance score for each attribute level. The marginal rate of substitution (MRS) was used to quantify the amount of overall survival (OS) physicians were willing to trade for a reduction in treatment-related adverse events (AEs). We further conducted the exploratory analysis, stratifying physicians from 5 perspectives into different subgroups and examining the treatment preferences and OS trade-off in each subgroup. Results: In terms of efficacy attributes, physicians placed greater emphasis on OS than time to pain progression. With regard to safety attributes, serious fracture was perceived as the most important AE by physicians, followed by serious fall, cognitive problems, skin rash, and fatigue. In the exploratory analysis, we found generally that physicians with less clinical practice experience and those from more economically developed regions placed more emphasis on AEs and were willing to give up more of their patients' OS to reduce the risk of AEs. Conclusion: Physicians from mainland China value the importance of minimizing treatment-related AEs when considering different treatment options for patients with nmCRPC, and they are willing to trade a substantial amount of OS to avoid AEs.

Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma.

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.

Minor Spliceosomal 65K/RNPC3 Interacts with ANKRD11 and Mediates HDAC3-Regulated Histone Deacetylation and Transcription.

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA- and other RNA-processing machineries in the nucleus. However, these established couplings are all major spliceosome-related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural-related defects. The 65K-ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle-uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin-binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11-KD are due to the decreased common chromatin-binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

Experimental Realization of Self-Contained Quantum Refrigeration.

A fundamental challenge in quantum thermodynamics is the exploration of inherent dimensional constraints in thermodynamic machines. In the context of two-level systems, the most compact refrigerator necessitates the involvement of three entities, operating under self-contained conditions that preclude the use of external work sources. Here, we build such a smallest refrigerator using a nuclear spin system, where three distinct two-level carbon-13 nuclei in the same molecule are involved to facilitate the refrigeration process. The self-contained feature enables it to operate without relying on net external work, and the unique mechanism sets this refrigerator apart from its classical counterparts. We evaluate its performance under varying conditions and systematically scrutinize the cooling constraints across a spectrum of scenarios, which sheds light on the interplay between quantum information and thermodynamics.

Determinants of macaques' space use: A test for the ecological constraints model using GPS collars.

As a central topic in Behavioral Ecology, animal space use involves dynamic responses to social and ecological factors. We collared 22 rhesus macaques (Macaca mulatta) from six groups on Neilingding Island, China, and collected 80,625 hourly fixes over a year. Using this high-resolution location data set, we quantified the macaques' space use at the individual level and tested the ecological constraints model while considering various environmental and human interfering factors. As predicted by the ecological constraints model, macaques in larger groups had longer daily path lengths (DPLs) and larger home ranges. We found an inverted U-shape relationship between mean daily temperatures and DPLs, indicating that macaques traveled farther on mild temperature days, while they decreased DPLs when temperatures were too high or too low. Anthropogenic food subsidies were positively correlated to DPLs, while the effect of rainfall was negative. Macaques decreased their DPLs and core areas when more flowers and less leaves were available, suggesting that macaques shifted their space use patterns to adapt to the seasonal differences in food resources. By applying GPS collars on a large number of individuals living on a small island, we gained valuable insights into within-group exploitation competition in wild rhesus macaques.

Site-specific thrombus formation: advancements in photothrombosis-on-a-chip technology.

Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels via laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.

FOXA1 Suppresses Endoplasmic Reticulum Stress, Oxidative Stress, and Neuronal Apoptosis in Parkinson's Disease by Activating PON2 Transcription.

Endoplasmic reticulum (ER) stress and oxidative stress (OS) are often related states in pathological conditions including Parkinson's disease (PD). This study investigates the role of anti-oxidant protein paraoxonase 2 (PON2) in ER stress and OS in PD, along with its regulatory molecule. PD was induced in C57BL/6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment and in SH-SY5Y cells using 1-methyl-4-phenylpyridinium. PON2 was found to be poorly expressed in the substantia nigra pars compacta (SNc) of PD mice, and its overexpression improved motor coordination of mice. Through the evaluation of tyrosine hydroxylase, dopamine transporter, reactive oxygen species (ROS), and C/EBP homologous protein (CHOP) levels and neuronal loss in mice, as well as the examination of CHOP, glucose-regulated protein 94 (GRP94), GRP78, caspase-12, sarco/endoplasmic reticulum calcium ATPase 2, malondialdehyde, and superoxide dismutase levels in SH-SY5Y cells, we observed that PON2 overexpression mitigated ER stress, OS, and neuronal apoptosis both in vivo and in vitro. Forkhead box A1 (FOXA1) was identified as a transcription factor binding to the PON2 promoter to activate its transcription. Upregulation of FOXA1 similarly protected against neuronal loss by alleviating ER stress and OS, while the protective roles were abrogated by additional PON2 silencing. In conclusion, this study demonstrates that FOXA1-mediated transcription of PON2 alleviates ER stress and OS, ultimately reducing neuronal apoptosis in PD.

Successful treatment of iatrogenic internal carotid artery pseudoaneurysm following carotid endarterectomy with thrombin injection: a case report.

BACKGROUND: Iatrogenic pseudoaneurysms arising from the internal carotid artery subsequent to carotid endarterectomy are exceptionally infrequent. Herein, we present a case detailing an internal carotid artery pseudoaneurysm that manifested subsequent to a hybrid carotid endarterectomy and endovascular therapy intervention. Our approach to managing this condition involved a novel technique wherein thrombin was directly injected into the luminal cavity of the pseudoaneurysm under the guidance of a C-arm. CASE PRESENTATION: A 66-year-old male patient of Chinese ethnicity exhibited a 4-month history of headache and a 20-day history of gait disturbance. Digital subtraction angiography revealed occlusion in the cervical region of the left carotid artery. Following a hybrid surgical procedure, the patient reported mild pain and bruising surrounding the incision site of the left internal carotid artery endarterectomy. Subsequent angiography identified the presence of a carotid artery pseudoaneurysm. Utilizing C-arm guidance, thrombin was then directly injected into the luminal cavity of the pseudoaneurysm, resulting in complete healing during follow-up. CONCLUSION: For the management of pseudoaneurysms arising post carotid endarterectomy, the direct injection of thrombin into the aneurysm cavity under the guidance of a C-arm is deemed both safe and efficacious.

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OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

Prognostic value of 17-Gene genomic prostate score in patients with clinically localized prostate cancer: a meta-analysis.

BACKGROUND: The 17-gene Genomic Prostate Score (GPS) test has been clinically employed to predict adverse prognosis in prostate cancer. In this meta-analysis, we aimed to evaluate the prognostic value of the 17-gene GPS in patients with prostate cancer. METHODS: Potentially relevant studies were obtained by searching PubMed, Web of Science, Embase databases from their inception to December 1, 2023. Studies were considered eligible if they evaluated the association of the 17-gene GPS with distant metastases, biochemical recurrence, or prostate cancer-specific mortality (PCSM) in prostate cancer patients. To estimate the prognostic value, we pooled the adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the high versus low GPS group or per 20-unit increase in GPS. RESULTS: Seven cohort studies that reported on 8 articles comprising 1,962 patients satisfied the eligibility criteria. Meta-analysis showed that per 20-unit increase in GPS was significantly associated with distant metastases (HR 2.99; 95% CI 1.97-4.53), biochemical recurrence (HR 2.18; 95% CI 1.64-2.89), and PCSM (HR 3.14; 95% CI 1.86-5.30). Moreover, patients with high GPS (> 40 points) had an increased risk of distant metastases (HR 5.22; 95% CI 3.72-7.31), biochemical recurrence (HR 4.41; 95% CI 2.29-8.49), and PCSM (HR 3.81; 95% CI 1.74-8.33) than those with low GPS (≤ 40 points). CONCLUSIONS: A higher 17-gene GPS significantly predicts distant metastases, biochemical recurrence, and PCSM in men with clinically localized prostate cancer. However, large-scale multicenter prospective studies are necessary to further validate these findings.

Cancer cachexia as a predictor of adverse outcomes in patients with non-small cell lung cancer: A meta-analysis.

INTRODUCTION: Cancer cachexia is a complex problem characterized by weight loss due to skeletal muscle and adipose tissue reduction. The purpose of this meta-analysis is to examine the association between cancer cachexia and adverse outcomes in patients with non-small cell lung cancer (NSCLC). METHODS: A comprehensive search was conducted in the PubMed, Web of Science, and Embase databases from their inception to January 15, 2024. Retrospective or prospective studies that investigated the cancer cachexia as a predictor of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), or disease control rate (DCR) in NSCLC patients were included in this analysis. RESULTS: Sixteen studies, comprising 5919 NSCLC patients, were identified. The pooled prevalence of cachexia in NSCLC patients was 39%, with individual studies reporting rates ranging from 19% to 63.8%. A meta-analysis using a random effects model showed that cachexia was associated with reduced OS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.54-2.21) and PFS (HR 1.49; 95% CI 1.27-1.73). Subgroup analysis indicated that cancer cachexia significantly predicted OS, regardless of study design, NSCLC subtypes, cancer stage, definitions of cachexia, or follow-up duration. However, there was no clear association between cancer cachexia and ORR or DCR. CONCLUSIONS: Cancer cachexia emerges is a negative prognostic factor for OS and PFS in NSCLC patients. Assessing cancer cachexia can improve risk classification for survival outcomes in this patient population.

Corn Silk Polysaccharide Reduces the Risk of Kidney Stone Formation by Reducing Oxidative Stress and Inhibiting COM Crystal Adhesion and Aggregation.

The aim of this study is to explore the inhibition of nanocalcium oxalate monohydrate (nano-COM) crystal adhesion and aggregation on the HK-2 cell surface after the protection of corn silk polysaccharides (CSPs) and the effect of carboxyl group (-COOH) content and polysaccharide concentration. METHOD: HK-2 cells were damaged by 100 nm COM crystals to build an injury model. The cells were protected by CSPs with -COOH contents of 3.92% (CSP0) and 16.38% (CCSP3), respectively. The changes in the biochemical indexes of HK-2 cells and the difference in adhesion amount and aggregation degree of nano-COM on the cell surface before and after CSP protection were detected. RESULTS: CSP0 and CCSP3 protection can obviously inhibit HK-2 cell damage caused by nano-COM crystals, restore cytoskeleton morphology, reduce intracellular ROS level, inhibit phosphoserine eversion, restore the polarity of the mitochondrial membrane potential, normalize the cell cycle process, and reduce the expression of adhesion molecules, OPN, Annexin A1, HSP90, HAS3, and CD44 on the cell surface. Finally, the adhesion and aggregation of nano-COM crystals on the cell surface were effectively inhibited. The carboxymethylated CSP3 exhibited a higher protective effect on cells than the original CSP0, and cell viability was further improved with the increase in polysaccharide concentration. CONCLUSIONS: CSPs can protect HK-2 cells from calcium oxalate crystal damage and effectively reduce the adhesion and aggregation of nano-COM crystals on the cell surface, which is conducive to inhibiting the formation of calcium oxalate kidney stones.

Impacts of medication adherence and home healthcare on the associations between polypharmacy and the risk of severe hypoglycemia among elderly diabetic patients in Taiwan from 2002 to 2012: A nationwide case-crossover study.

AIM: To assess how medication adherence and home healthcare support influence the role of polypharmacy in induced hypoglycemia events among elderly diabetic patients. METHODS: This case-crossover study retrieved records on diabetic patients >=65 years with severe hypoglycemia from 2002 to 2012 in Taiwan. Case period defined as 1-3 days before severe hypoglycemia was compared with a preceding control period of the same length, with an all-washout period of 30 days. Moreover, the modifiable effects of medication adherence and home healthcare service use were evaluated by stratified analysis. RESULTS: Totally 2,237 patients were identified. Polypharmacy use was associated with the risk of severe hypoglycemia. Patients receiving polypharmacy without home healthcare services (aOR: 1.34; 95 % CI: 1.16-1.54) and those with poor adherence to anti-diabetic medications (aOR: 1.48; 95 % CI: 1.24-1.77) were significantly associated with an elevated risk of severe hypoglycemia. In patients with good adherence, non-home healthcare users being prescribed with polypharmacy had a higher risk of severe hypoglycemia. In the group that received home healthcare services, patients with poor adherence using polypharmacy had a higher risk of severe hypoglycemia. CONCLUSIONS: Good adherence and receiving home healthcare services were associated with a decreased odds of severe hypoglycemic events in elderly diabetic patients, regardless of the fact whether they were prescribed with polypharmacy.

The correlation between time-intensity curve parameters of transrectal contrast-enhanced ultrasound and pathological prognostic factors in rectal adenocarcinoma.

AIMS: To investigate the correlation between time-intensity curve (TIC) parameters obtained from transrectal contrast-enhanced ultrasound (TR-CEUS) and important pathological prognostic factors in rectal adenocarcinoma. MATERIAL AND METHODS:  We retrospectively included 477 patients with pathologically confirmed rectal adenocarcinoma. TIC parameters were derived from preoperative dynamic TR-CEUS images. These parameters included peak intensity (PI), time to peak (TTP),mean transit time (MTT), slope (S), and area under the curve (AREA). Pathological prognostic factors included TN stage, tumor diameter, lymphovascular invasion (LVI), perineural invasion, and tumor differentiation. Spearman's correlation analysis and binary logistic regression were used to analyze the association between TIC parameters and pathological prognostic factors. RESULTS: pT1-2 stages rectal carcinomas exhibited higher PI-max, PI-min, S-max, S-min, AREA-max, and AREA-min than pT3-4 stages (all p<0.05). pN0 stage rectal adenocarcinomas displayed higher PI-max, S-max, AREA-max, PI-ratio, Sratio, and AREA-ratio than pN1-2 stage (all p<0.05). PI-ratio and S-ratio were higher in the LVI-negative and tumor diameter ≥4cm group compared to the LVI-positive and tumor diameter <4cm group, respectively (p<0.05). Well-differentiated rectal adenocarcinomas displayed higher PI-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio than the moderate-poor differentiated group (all p<0.05). PI-max, S-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio were negatively correlated with pN stage (all p<0.05). PI-ratio and S-ratio were independent predictive factors for the pN stage (OR=0.774, OR=1.048). S-ratio and AREA-ratio were independent predictive factors for tumor differentiation (OR=1.071, OR=0.911). CONCLUSIONS: TIC parameters derived from TR-CEUS exhibit correlations with specific pathological prognostic factors in rectal adenocarcinomas. This non-invasive method may hold promise for preoperatively assessing the prognosis of rectal adenocarcinoma patients.