Efficacy and safety of PD-1/PD-L1 inhibitors in elderly patients with advanced non-small cell lung cancer.

OBJECTIVE: This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC ≥70 years old who received PD-1/PD-L1 inhibitors in our hospital were retrospectively analyzed. According to age, the patient were stratified as follows: 70-75 years old, 76-80 years old, and >80 years old. Kaplan-Meier method was used for survival analysis, and univariate and multivariate Cox proportional hazards regression models were used to analyze the correlation between different clinical characteristics and survival. RESULTS: A total of 58 elderly patients with advanced non-small cell cancer were enrolled in this study. Patients aged 70-75, 76-80, and >80 years old were 32, 19, and 7, respectively. For the all, median OS was 17.0 months, and PFS was 7.0 months. PFS and OS did not differ according to age (P = 0.396, 0.054, respectively). Univariate analysis showed that PS of 0-1, stage III, first-line therapy and irAEs were associated with longer PFS, and PS of 0-1, stage III, and first-line therapy were associated with longer OS. Multivariate analysis showed that patients with stage III had longer PFS. PFS and OS of patients with PS ≥ 2 were significantly shorter than those of patients with PS of 0-1. CONCLUSIONS: In the present real-world retrospective cohort, PD-1/PD-L1 inhibitors are effective and well tolerated in elderly patients with advanced NSCLC. Immunotherapy should be actively used as early as possible in older patients advanced NSCLC.

Curcumin Inhibits the Progression of Non-small Cell Lung Cancer by Regulating DMRT3/SLC7A11 Axis.

Non-small cell lung cancer (NSCLC) is a fatal malignancy all over the world. Emerging studies have shown that curcumin might repress NSCLC progression by regulating ferroptosis, but the underlying mechanism remains unclear. 16HBE, LK-2, and H1650 cell viability was detected using Cell Counting Kit-8 assay. LK-2 and H1650 cell proliferation, apoptosis, and angiopoiesis were measured using 5-ethynyl-2'-deoxyuridine, flow cytometry, and tube formation assay. Superoxide dismutase, Malondialdehyde, Glutathione, and lactate dehydrogenase levels in LK-2 and H1650 cells were examined using special assay kits. Fe+ level was assessed using an iron assay kit. Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) and solute carrier family 7 member 11 (SLC7A11) protein levels were detected using western in NSCLC tissues, adjacent matched normal tissues, 16HBE cells, LK-2 cells, H1650 cells, and xenograft tumor tissues. Glutathione peroxidase 4, Acyl-CoA Synthetase Long Chain Family Member 4, and transferrin receptor 1 protein levels in LK-2 and H1650 cells were examined by western blot assay. DMRT3 and SLC7A11 levels were determined using real-time quantitative polymerase chain reaction. After JASPAR prediction, binding between DMRT3 and SLC7A11 promoter was verified using Chromatin immunoprecipitation and dual-luciferase reporter assays in LK-2 and H1650 cells. Role of curcumin on NSCLC tumor growth was assessed using the xenograft tumor model in vivo. Curcumin blocked NSCLC cell proliferation and angiopoiesis, and induced apoptosis and ferroptosis. DMRT3 or SLC7A11 upregulation partly abolished the suppressive role of curcumin on NSCLC development. In mechanism, DMRT3 was a transcription factor of SLC7A11 and increased the transcription of SLC7A11 via binding to its promoter region. Curcumin inhibited NSCLC growth in vivo by modulating DMRT3. Curcumin might constrain NSCLC cell malignant phenotypes partly through the DMRT3/SLC7A11 axis, providing a promising therapeutic strategy for NSCLC.

Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription.

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping.

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

Content of medicine prescription and clinical practice training for haematology advanced practice nurses in China: A modified Delphi study.

AIM: To explore the scope and form of prescriptions for blood and hematopoietic drugs that future advanced practice nurses (APNs) in the Department of Haematology and to establish a medicine prescription training content in China. BACKGROUND: Because the increasing number of doctors cannot meet the increasing demand for medical care with the population growth, many countries have begun to explore the medical team structure and practice areas, among which nurse prescribing rights have been the most effective. However, China's higher nursing education system still lacks education and training on nurse prescription. DESIGN: On the basis of literature research and semi-structured interviews, a set of nursing prescription content, education, training and practice system suitable for Chinese nurses was jointly created. METHODS: Two rounds of expert consultation between 23 haematology nursing experts and clinical experts determined the training content of blood system drugs and medicine prescriptions. Additionally, on the basis of the 23 experts，13 experts engaged in clinical and education, teaching and training experts were involved. Two rounds of expert consultation with 36 experts identified a general clinical practice training program for advanced practice nurses in China. RESULTS: Regarding contents and forms of hematopoietic drugs, the study concluded that advanced practice nurses in haematology department can prescribe anti-anemia drugs, anti-coagulant drugs and anti-thrombotic drugs in 2 categories and 16 drugs. Of these, four kinds of drugs should be prescribed in the form of protocol prescription. One kind of drug should be prescribed in the form of extended prescription and 11 drugs should be prescribed in the form of independent/extended or agreed/extended prescription. Regarding training content, the study obtained the training content of nurses' medicine prescriptions in eight clinical circumstances and the medicine prescription training content for common diseases of the blood system. The required specifications and the medicine prescription decision skills of nurses were sorted out according to different prescription types. CONCLUSIONS: The degrees of expert authority were both higher in consultations. Moreover, the results after consultation were reliable. It was recommended that haematology APNs could prescribe anti-anaemic drugs and anti-coagulation and anti-thrombotic drugs. Furthermore, most drugs should be prescribed in the form of independent/extended or agreed/extended prescriptions. The establishment of a medicine prescription training content for haematology APNs is expected to provide a reference for clinical practice education and training for drug prescriptive authority applicants for blood and hematopoietic system nurses in China.

Construction of a 3D Quantum Dot Nanoassembly with Two-Step FRET for One-Step Sensing of Human Telomerase RNA in Breast Cancer Cells and Tissues.

Telomerase is an important biomarker for early diagnosis of cancers, but current telomerase assays usually rely on measuring the extension products of telomerase substrates, which increases the assay complexity. More evidence indicates that human telomerase RNA (hTR), as a core component of telomerase, is positively correlated with the telomerase activity. Herein, we demonstrate the development of a duplex-specific nuclease (DSN)-propelled 3D quantum dot (QD) nanoassembly with two-step Föster resonance energy transfer (FRET) for the one-step sensing of hTR in breast cancer cells and tissues. This assay involves only one hairpin probe modified with a Cy5 at the sixth base from the 5'-biotin end and a BHQ2 at the 3'-terminus, which integrates three functions of target recognition, target recycling amplification, and signal readout. The anchoring of the hairpin probe on the 605QD surface results in the formation of a 3D 605QD-Cy5-probe-BHQ2 nanoassembly in which two-step FRET occurs among the 605QD, Cy5, and BHQ2 quencher. Notably, the formation of 605QD-Cy5-probe-BHQ2 nanoassembly facilitates the reduction of background signal and the increase of signal-to-background ratio due to its dense, highly oriented nucleic acid shell-induced steric hindrance effect. This assay can achieve one-step and rapid detection of hTR with a detection limit of 2.10 fM, which is the simplest and most rapid hTR assay reported so far. Moreover, this assay can efficiently distinguish single-base mismatched sequences, and it can discriminate the hTR level between breast cancer patients and healthy donors with a high accuracy of 100%, with great prospects for early diagnosis of cancers.

Cellulose-based biomass composite films for plastic replacement: Synergistic UV shielding, antibacterial and antioxidant properties.

With the gradual increase in environmental awareness and the growing demand for food safety, sustainable and environmentally friendly cellulose-based materials have become a promising alternative to petroleum-based plastics. However, in practice, packaging materials prepared from cellulose-based materials still have some unsatisfactory properties, such as monofunctionality, low transparency, and lack of UV shielding, antibacterial or antioxidant properties. Herein, a novel synthetic strategy is proposed in this paper, specifically, tannic acid (TA), a green natural extract with antibacterial and antioxidant properties, is used as a plasticizer and cross-linker, and oxidized cellulose nanocellulose (TOCN) modified with folic acid (FA) grafting is blended with TA, and cellulose-based biomass thin films with ultraviolet (UV) shielding, antibacterial, and antioxidant properties have been successfully prepared by using a simple vacuum-assisted filtration. The experimental results showed that the films could completely block ultraviolet light at wavelengths of 200-400 nm while providing 81.47 % transparency in the visible spectrum, while the introduction of TA conferred excellent antibacterial and antioxidant capabilities with antioxidant activity of up to 95 %, and also resulted in films with excellent mechanical properties. Therefore, this work provides ideas for the design and manufacture of competitive biomass green packaging materials, laying the foundation for future applications in food packaging.

The function and application of edible fungal polysaccharides.

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Edible fungal polysaccharides (EFPs) are a variety of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Increasing researches have confirmed that EFPs possess multiple biological activities both in vitro and in vivo settings, including antioxidant, antiviral, anti-inflammatory, immunomodulatory, anti-tumor, hypoglycemic, hypolipidemic, and regulating intestinal flora activities. As a result, they have emerged as a prominent focus in the healthcare, pharmaceutical, and cosmetic industries. Fungal EFPs have safe, non-toxic, biodegradable, and biocompatible properties with low immunogenicity, bioadhesion ability, and antibacterial activities, presenting diverse potential applications in the food industries, cosmetic, biomedical, packaging, and new materials. Moreover, varying raw materials, extraction, purification, chemical modification methods, and culture conditions can result in variances in the structure and biological activities of EFPs. The purpose of this review is to provide comprehensively and systematically organized information on the structure, modification, biological activities, and potential applications of EFPs to support their therapeutic effects and health functions. This review provides new insights and a theoretical basis for prospective investigations and advancements in EFPs in fields such as medicine, food, and new materials.

Triple semicircular canal occlusion with endolymphatic sac decompression for intractable Meniere's disease.

Background: Meniere's disease (MD) is characterized by idiopathic endolymphatic hydrops (ELH). Frequent vertigo attacks is the most disabling symptom of MD. Objective: This study evaluated the efficacy of triple semicircular canal occlusion combined with endolymphatic sac decompression in the treatment of frequent vertigo in patients with MD. Methods: Eleven patients with complete medical records were included in this study conducted from May 2021 to April 2022. All patients were enrolled to undergo triple semicircular canal occlusion (TSCO) with endolymphatic sac decompression (ESD). Various tests including pure tone audiometry (PTA), vestibular evoked myogenic potentials (VEMPs), the video head impulse test (v-HIT), caloric test data, the Dizziness Handicap Inventory (DHI), the Berg Balance Scale (BBS), and the Tinnitus Handicap Inventory (THI) were performed both before and after the surgery. Results: The successful control rate of vertigo was 100% (9/9) in the average 23-month postoperative follow-up period, with complete control rate of 88.89% (8/9) and substantial control rate of 11.11% (1/9). Conclusion: Triple semicircular canal occlusion combined with ESD may be an effective treatment option for managing frequent vertigo attacks in patients with MD. This combination therapy has the potential to become a significant addition to the treatment framework for MD.

Nosocomial Infections After Pediatric Congenital Heart Disease Surgery: Data from National Center for Cardiovascular Diseases in China.

Purpose: Infection prevention and control (IPC) has a significant impact on the prognosis after pediatric cardiac surgery. This study aimed to provide surveillance data on the incidence and density of various infections during the COVID-19 epidemic and explore the influence of multi-drug resistant organisms (MDRO) on in-hospital prognosis after congenital heart disease surgery. Methods: This single-center retrospective study included pediatric patients who underwent cardiac surgery between 2021 and 2022. The results of the postoperative bacterial and fungal cultures and antimicrobial stewardship were collected. The demographic characteristics (age and weight), operation-related parameters (RACHS-1 grade, duration of cardiopulmonary bypass, and aortic cross clamp), and surgical outcomes (extracorporeal membrane oxygenation, delayed sternal closure, mortality, duration of mechanical ventilation, length of intensive care unit stay and hospital stay, and hospitalization costs) of MDRO and non-MDRO patients were compared. Results: A total of 4776 patients were included. There were 101 infectious culture results after the operation, with a nosocomial infection rate of 2.1%. There were 40 MDRO specimens from 36 patients, 50 non-MDRO specimens from 30 patients, and 11 fungal specimens from 10 patients. The incidence of pneumonia was 1.5%, with a ventilator-associated pneumonia incidence density of 7.2/1000 patient-days. The incidence of sepsis was 0.4%, with a catheter-related bloodstream infection incidence density of 0.24/ 1000 patient-days. The incidence density of catheter-associated tract infection was 0.45/ 1000 patient-days. The incidence of surgical site infection was 0.06%. The culture proportion before commencing antibiotics was 93% and the antibiotic consumption intensity was 30.7 DDD/100 bed-days. The length of intensive care unit stay in MDRO infection patients increased compared with that in non-MDRO infection patients, 30 (18,52) vs 17 (7,62) days, p=0.05). Conclusion: The IPC performance of Fuwai Hospital achieved satisfactory results. MDRO infection can lead to prolonged intensive care unit stay.

Developed countries have advanced infection prevention and control systems and comprehensive postoperative infection monitoring data for congenital heart disease. While developing countries have initiated efforts in infection prevention and control, global attention remains substantial. This study aimed to provide comprehensive infection surveillance data and identify possible implementation for further improvement in the National Center for Cardiovascular Diseases in China (Fuwai Hospital). This was a retrospective single-center study. We included pediatric patients who underwent cardiac surgery at a pediatric surgical center between 2021 and 2022, with an age limit of 14 years. Exclusion criteria included patients undergoing medical therapy, interventional therapy, or surgical therapy in other centers in Fuwai Hospital. This study, for the first time, reports the incidence of comprehensive healthcare-associated infection surveillance and targeted surveillance (encompassing device-associated infection, surgical site infection, and multi-drug resistant organisms) after pediatric cardiac surgery at the National Center for Cardiovascular Diseases in China. In addition, we report the data on antimicrobial stewardship. We compared the surgical outcome and hospitalization costs between patients with multi-drug resistant organism infection and those without multi-drug resistant organism infection and found that multi-drug resistant organism infection can lead to prolonged intensive care unit length of stay. The Fuwai Hospital achieved satisfactory infection prevention and control results. However, because China is a large developing country exhibiting notable variations in medical conditions across its diverse regions, prospective, multicenter, observational studies should be carried out for future research based on existing evidence.

Rapid quantitative authentication and analysis of camellia oil adulterated with edible oils by electronic nose and FTIR spectroscopy.

Camellia oil, recognized as a high-quality edible oil endorsed by the Food and Agriculture Organization, is confronted with authenticity issues arising from fraudulent adulteration practices. These practices not only pose health risks but also lead to economic losses. This study proposes a novel machine learning framework, referred to as a transformer encoder backbone with a support vector machine regressor (TES), coupled with an electronic nose (E-nose), for detecting varying adulteration levels in camellia oil. Experimental results indicate that the proposed TES model exhibits the best performance in identifying the adulterated concentration of camellia oi, compared with five other machine learning models (the support vector machine, random forest, XGBoost, K-nearest neighbors, and backpropagation neural network). The results obtained by E-nose detection are verified by complementary Fourier transform infrared (FTIR) spectroscopy analysis for identifying functional groups, ensuring accuracy and providing a comprehensive assessment of the types of adulterants. The proposed TES model combined with E-nose offers a rapid, effective, and practical tool for detecting camellia oil adulteration. This technique not only safeguards consumer health and economic interests but also promotes the application of E-nose in market supervision.

Preoperative CECT-Based Multitask Model Predicts Peritoneal Recurrence and Disease-Free Survival in Advanced Ovarian Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: Peritoneal recurrence is the predominant pattern of recurrence in advanced ovarian cancer (AOC) and portends a dismal prognosis. Accurate prediction of peritoneal recurrence and disease-free survival (DFS) is crucial to identify patients who might benefit from intensive treatment. We aimed to develop a predictive model for peritoneal recurrence and prognosis in AOC. METHODS: In this retrospective multi-institution study of 515 patients, an end-to-end multi-task convolutional neural network (MCNN) comprising a segmentation convolutional neural network (CNN) and a classification CNN was developed and tested using preoperative CT images, and MCNN-score was generated to indicate the peritoneal recurrence and DFS status in patients with AOC. We evaluated the accuracy of the model for automatic segmentation and predict prognosis. RESULTS: The MCNN achieved promising segmentation performances with a mean Dice coefficient of 84.3% (range: 78.8%-87.0%). The MCNN was able to predict peritoneal recurrence in the training (AUC 0.87; 95% CI 0.82-0.90), internal test (0.88; 0.85-0.92), and external test set (0.82; 0.78-0.86). Similarly, MCNN demonstrated consistently high accuracy in predicting recurrence, with an AUC of 0.85; 95% CI 0.82-0.88, 0.83; 95% CI 0.80-0.86, and 0.85; 95% CI 0.83-0.88. For patients with a high MCNN-score of recurrence, it was associated with poorer DFS with P < 0.0001 and hazard ratios of 0.1964 (95% CI: 0.1439-0.2680), 0.3249 (95% CI: 0.1896-0.5565), and 0.3458 (95% CI: 0.2582-0.4632). CONCLUSION: The MCNN approach demonstrated high performance in predicting peritoneal recurrence and DFS in patients with AOC.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Occurrence and combined exposure of phthalate esters in urban soil, surface dust, atmospheric dustfall, and commercial food in the semi-arid industrial city of Lanzhou, Northwest China.

A total of 138 samples including urban soil, surface dust, atmospheric dustfall, and commercial food were collected from the semi-arid industrial city of Lanzhou in Northwest China, and 22 phthalate esters (PAEs) were analyzed in these samples by gas chromatography-mass spectrometry for the pollution characteristics, potential sources, and combined exposure risks of PAEs. The results showed that the total concentration of 22 PAEs (Æ©22PAEs) presented surface dust (4.94 × 104 ng/g) â‰« dustfall (1.56 × 104 ng/g) â‰« food (2.14 × 103 ng/g) â‰« urban soil (533 ng/g). Di-n-butyl phthalate (DNBP), di-isobutyl phthalate, di(2-ethylhexyl) phthalate (DEHP), and di-isononyl phthalate/di-isodecyl phthalate were predominant in the environmental media and commercial food, being controlled by priority (52.1%-65.5%) and non-priority (62.1%) PAEs, respectively. Elevated Æ©22PAEs in the urban soil and surface dust was found in the west, middle, and east of Lanzhou. Principal component analysis indicated that PAEs the urban soil and surface dust were related with the emissions of products containing PAEs, atmosphere depositions, and traffic and industrial emissions. PAEs in the foods were associated with the growth and processing environment. The health risk assessment of United States Environmental Protection Agency based on the Chinese population exposure parameters indicated that the total exposure dose of 22 PAEs was from 0.111 to 0.226 mg/kg/day, which were above the reference dose (0.02 mg/kg/day) and tolerable daily intake (TDI, 0.05 mg/kg/day) for DEHP (0.0333-0.0631 mg/kg/day), and TDI (0.01 mg/kg/day) for DNBP (0.0213-0.0405 mg/kg/day), implying that the exposure of PAEs via multi-media should not be ignored; the total non-carcinogenic risk of six priority PAEs was below 1 for the three environmental media (1.21 × 10-5-2.90 × 10-3), while close to 1 for food (4.74 × 10-1-8.76 × 10-1), suggesting a potential non-carcinogenic risk of human exposure to PAEs in food; the total carcinogenic risk of BBP and DEHP was below 1 × 10-6 for the three environmental media (9.13 × 10-10-5.72 × 10-7), while above 1 × 10-4 for DEHP in food (1.02 × 10-4), suggesting a significantly carcinogenic risk of human exposure to DEHP in food. The current research results can provide certain supports for pollution and risk prevention of PAEs.

MDM2: current research status and prospects of tumor treatment.

Mousedouble minute 2 (MDM2) is one of the molecules activated by p53 and plays an important role in the regulation of p53. MDM2 is generally believed to function as a negative regulator of p53 by facilitating its ubiquitination and subsequent degradation. Consequently, blocked p53 activity often fails in damaged cells to undergo cell cycle arrest or apoptosis. Given that around 50% of human cancers involve the inactivation of p53 through genetic mutations, and directly targeting p53 through drug development has limited feasibility, targeting molecular regulation related to p53 has great potential and has become a research hotspot. For example, developing drugs that target the interaction between p53 and MDM2. Such drugs aim to reactivate p53 by targeting either MDM2 binding or p53 phosphorylation. Researchers have identified various compounds that can serve as inhibitors, either by directly binding to MDM2 or by modifying p53 through phosphorylation. Furthermore, a significant correlation exists between the expression of MDM2 in tumors and the effectiveness of immunotherapy, predominantly in the context of immune checkpoint inhibition. This review presents a comprehensive overview of the molecular characteristics of MDM2 and the current state of research on MDM2-targeting inhibitors. It includes a review of the impact of MDM2 targeting on the efficacy of immunotherapy, providing guidance and direction for the development of drugs targeting the p53-MDM2 interaction and optimization of immunotherapy.

Application of Situational Simulation Teaching Method in Respiratory and Cardiac Arrest Induced by Aspiration in Elderly Patients.

Background: Elderly hospitalized patients often have dysphagia, which can cause a variety of complications, the most common being aspiration. Early detection and timely treatment by nurses are needed in the clinic. Objective: To assess the effect of the situational simulation teaching method in respiratory and cardiac arrest induced by aspiration in elderly patients. Design: This was a retrospective study. Setting: This study was performed in the Department of Geriatrics, The Third Hospital of Hebei Medical University. Participants: Fifty patients with aspiration-induced respiratory and cardiac arrest who were hospitalized in our hospital were chosen and divided into 2 groups according to the composition of rescue nursing staff, and each group had 25 cases. Interventions: The patients who were rescued by nurses without scenario simulation training were the control group (routine emergency nursing group). The patients who were rescued by nurses trained via the scenario simulation teaching method were the experimental group. Primary Outcome Measures: (1) Emergency rescue time, (2) survival rate, (3) duration of adverse events, and (4) nursing satisfaction of patients. Results: Compared to the control group, the emergency rescue time, the duration of asphyxia, duration of respiratory and cardiac arrest, and the duration of malignant arrhythmias caused by cardiac arrest in the experimental group was lower (P < .05), while the survival rate and nursing satisfaction of patients in the experimental group was higher (P < .05). Conclusion: The application of situational simulation teaching method in the rescue of patients with respiratory and cardiac arrest has outstanding effects, which can effectively improve the efficiency of first aid, significantly improve the efficiency and standardization of first aid, and control or prevent the occurrence of poor prognosis, which is worth popularizing.

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.

BACKGROUND: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. METHODS: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. RESULTS: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. CONCLUSION: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

TRIB3 promotes the progression of renal cell carcinoma by upregulating the lipid droplet-associated protein PLIN2.

Abnormal lipid metabolism and lipid accumulation are characteristic hallmarks of renal cell carcinoma (RCC). While there is prior evidence closely linking such lipid accumulation within RCC cells and consequent tumorigenesis, the mechanisms underlying this process remain incompletely understood. In this study, a series of bioinformatics analyses were initially performed by screening RCC databases and gene sets, ultimately leading to the identification of TRIB3 as an oncogene that functions as a central regulator of lipid metabolism. TRIB3 overexpression was observed in both RCC patient tumor tissues and cell lines, and this upregulation was correlated with a worse RCC patient prognosis. When TRIB3 was knocked down, this resulted in a reduction in lipid accumulation and the consequent induction of endoplasmic reticulum (ER) stress-related apoptotic cell death. At the molecular level, interactions between TRIB3 and PLIN2 were found to abrogate TEB4-mediated PLIN2 ubiquitination and consequent degradation, thus maintaining higher PLIN2 expression levels. This simultaneously helps facilitate the accumulation of lipids while preserving ER homeostasis, thus driving accelerated RCC tumor progression. This TRIB3-PLIN2 axis thus represents a promising new target for efforts to treat RCC.