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Abstract Cancer affects patients as well as their spouses. Patients and their spouses use different strategies to cope with cancer and the associated burden. This study aimed to gain a deeper and more differentiated understanding of support systems for patients and their spouses. This was an exploratory qualitative study conducted in China. The study was based on 20 semistructured face-to-face interviews. Ten pancreatic cancer patients and their spouses were interviewed. The interviews took place at a tertiary hospital from June 2023 to December 2023. The data were analysed using thematic analysis according to Braun and Clarke's methodology. This study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Twenty participants of different ages (patients: range = 49–75 years; spouses: range = 47–73 years) participated. Patients with different cancer stages (e.g., potentially resectable, borderline resectable, locally advanced) and cancer types (initial diagnosis or relapse) participated in the study. Five themes emerged from the data, namely, denial and silence, fear and worry, struggle, coping strategies and cherishing the present. Active dyadic coping is conducive to promoting disease adaptation, and spouses seem to need more psychological support to improve their own well-being. Health care providers should pay attention to pancreatic cancer patients and their spouses in terms of five themes: denial and silence, fear and worry, struggle, coping strategies and cherishing the present. Future studies should use a combination of qualitative and quantitative methods to explore dyadic coping in greater depth.

Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties, e.g., Mfsd2a-mediated BTB low transcytosis. Here, we reported VCAM-1-targeting nano-wogonin (W@V-NPs) as an adjuvant of nano-orlistat (O@V-NPs) to intensify drug delivery and inhibit lipogenesis of brain metastases. W@V-NPs were proven to be able to inactivate BTB Wnt signaling, downregulate BTB Mfsd2a, accelerate BTB vesicular transport, and enhance tumor accumulation of O@V-NPs. With the ability to specifically kill cancer cells in a lipid-deprived environment with IC50 at 48 ng/mL, W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice. The combination did not induce brain edema, cognitive impairment, and systemic toxicity in healthy mice. Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

This is an article in the field of ceramics and composites. In order to improve the impermeability and microstructure of the impermeable wall materials, four kinds of calcium-based bentonite modified and filling material with different dosages were prepared under the action of alkali excitation reaction. The modified and filling material samples in the curing process were tested by flexible wall penetration (FWPT), nuclear magnetic resonance (NMR) scanning and electron microscope scanning (SEM). The results show that the permeability coefficient of filling material samples decreases first and then increases with the increase of bentonite content, and reaches a minimum value when the content of bentonite is 4%. The relaxation time (T2) distribution curves of the filled material specimens after curing from 1 to 28 d were all bimodal, with more than 80% of the peaks representing small pores, and the percentage of the peaks representing large pores decreasing with the increase of curing time. According to SEM images, it can be seen that a certain amount of calcium bentonite can promote the occurrence of hydration reaction, and the porosity of the material is significantly reduced. At 4% phosphate slag, the cementitious filler has the best compactness and better impermeability and strength. Accordingly, it can be determined that the better dosage of phosphate slag modified cementitious filler is 4%.

F. taipaiensis P. Y. Li represents a significant asset within traditional Chinese medicinal flora, though it confronts the challenge of germplasm deterioration during its cultivation phase. This study aimed to discern the implications of single strains or combinations of diverse growth-promoting actinomycetes on the growth metrics, antioxidant competence and pertinent gene expression in the leaves of F. taipaiensis. The result revealed that the malondialdehyde content within the plant's leaves notably diminished in the treatment groups compared to the CK group, with the S6 group showcasing the most pronounced malondialdehyde reduction, amounting to approximately one-third of the CK's value. Leaf area, length and width peaked in the S5 cohort, registering values 4.55, 2.46 and 1.85 times surpassing the CK group. Concurrently, plant height and stem thickness were maximal in the S6 group, being 2.29 and 1.75 times that of the CK group, whereas leaf thickness reached its zenith in the S7 group, marking a 2.17-fold elevation compared to the CK. Photosynthetic pigments, soluble sugars and soluble proteins in the leaves, exhibited augmentation across the inoculated groups to varying magnitudes. Specifically, the S5 group was superior in photosynthetic metrics and pigments, while the S6 group manifested the highest soluble sugar concentration, which was 1.35 times that of the CK. The S3 group demonstrated the pinnacle of soluble protein content, an impressive 5.86-fold increment relative to the CK group. The enzymatic activities of superoxide dismutase, peroxidase and catalase, along with their affiliated gene expressions, were observably augmented in the inoculated groups, with the S5 group standing out. To encapsulate, the actinomycete inoculation holds potential in fostering the growth and maturation of F. taipaiensis, amplifying its environmental resilience. The revelations from this study extend valuable insights for the judicious choice of microbial fertilizers in the cultivated propagation of Fritillaria taipaiensis P. Y. Li.

Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.

Gastric cancer (GC) is a common malignant tumor that is pernicious to the health of patients. Proteasome activator subunit 3 (PSME3) has been shown to exhibit higher expression and aggravate tumorigenesis in cancer progression. A major finding is that PSME3 is also highly expressed in GC tissues, which results in a worse prognosis. Nevertheless, the regulatory functions of PSME3 in GC progression remain unclear. This study aimed to investigate the impacts of PSME3 and related regulatory pathways on GC progression. From the Gene Expression Profiling Interactive Analysis (GEPIA) database, it was noted that PSME3 expression was up-regulated in GC tissues. Our findings suggested that in GC, PSME3 showed higher expression, resulting in a worse prognosis. Functional experiments revealed that PSME3 accelerates cell growth, migration and abnormal glycolysis in GC. PSME3 stimulates the epidermal growth factor receptor (EGFR)/c-myc pathway. In conclusion, GC cells exhibited higher PSME3 expression, which modulated the EGFR/c-myc pathway to facilitate glycolysis and migration. PSME3 might be an effective bio-target for GC treatment.

Abstract Controversy surrounds the role of serum uric acid and whether treatment intervention is favorable in retarding the progression of chronic kidney disease (CKD). The association of serum uric acid levels and CKD patient mortality risk needs to be further determined by large sample cohort studies. The National Health and Nutrition Examination Survey participants with CKD from 1998 to 2017 were enrolled in the study. Multivariable Cox regression models were used to reveal the association of serum uric acid concentrations and CKD mortality risks. A total of 9891 CKD patients were enrolled in the study, and 3698 individuals died during the follow-up. Increasing serum uric acid levels are independently relevant to higher mortality risks of CKD patients (HR per SD increase). A restricted cubic spline curve showed a nonlinear association between serum uric acid and CKD mortality risks (p for nonlinearity = 0.046). CKD patients with higher levels of serum uric acid (≥ 5.900 mg/dL) show a significant increase in mortality risks (HR = 1.102, 95% CI 1.043–1.165). Sensitivity analysis demonstrated that the results were stable and robust. High serum uric acid levels (≥ 5.900 mg/dL) may be associated with increased mortality risks in CKD patients.

BackgroundIncreasing cases of diabetes, a general lack of routinely operational prevention, and a long history of separating disease prevention and treatment call for immediate engagement of frontier clinicians. This applies especially to village doctors who work in rural China where the majority of the nation’s vast population lives. ObjectiveThis study aims to develop and test an online Smart Web Aid for Preventing Type 2 Diabetes (SWAP-DM2) capable of addressing major barriers to applying proven interventions and integrating diabetes prevention into routine medical care. MethodsDevelopment of SWAP-DM2 used evolutionary prototyping. The design of the initial system was followed by refinement cycles featuring dynamic interaction between development of practical and effective standardized operation procedures (SOPs) for diabetes prevention and Web-based assistance for implementing the SOPs. The resulting SOPs incorporated proven diabetes prevention practices in a synergetic way. SWAP-DM2 provided support to village doctors ranging from simple educational webpages and record maintenance to relatively sophisticated risk scoring and personalized counseling. Evaluation of SWAP-DM2 used data collected at baseline and 6-month follow-up assessment: (1) audio recordings of service encounters; (2) structured exit surveys of patients’ knowledge, self-efficacy, and satisfaction; (3) measurement of fasting glucose, body mass index, and blood pressure; and (4) qualitative interviews with doctors and patients. Data analysis included (1) descriptive statistics of patients who received SWAP-DM2–assisted prevention and those newly diagnosed with prediabetes and diabetes; (2) comparison of the variables assessed between baseline and follow-up assessment; and (3) narratives of qualitative data. ResultsThe 17 participating village doctors identified 2219 patients with elevated diabetes risk. Of these, 84.85% (1885/2219) consented to a fasting glucose test with 1022 new prediabetes and 113 new diabetes diagnoses made within 6 months. The prediabetic patients showed substantial improvement from baseline to 6-month follow-up in vegetable intake (17.0%, 43/253 vs 88.7%, 205/231), calorie intake (1.6%, 4/253 vs 71.4%, 165/231), leisure-time exercises (6.3%, 16/253 vs 21.2%, 49/231), body weight (mean 62.12 kg, SD 9.85 vs mean 58.33 kg, SD 9.18), and body mass index (mean 24.80 kg/m2, SD 3.21 vs mean 23.36 kg/m2, SD 2.95). The prediabetic patients showed improvement in self-efficacy for modifying diet (mean 5.31, SD 2.81 vs mean 8.53, SD 2.25), increasing physical activities (mean 4.52, SD 3.35 vs mean 8.06, SD 2.38), engaging relatives (mean 3.93, SD 3.54 vs mean 6.93, SD 2.67), and knowledge about diabetes and risks of an imbalanced diet and inadequate physical activity. Most participating doctors and patients viewed SWAP-DM2 as useful and effective. ConclusionsSWAP-DM2 is helpful to village doctors, acceptable to patients, and effective in modifying immediate determinants of diabetes at least in the short term, and may provide a useful solution to the general lack of participation in diabetes prevention by frontier clinicians in rural China. Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 66772711; http://www.controlled-trials.com/ISRCTN66772711 (Archived by WebCite at http://www.webcitation.org/6OMkAqyEy).

Abstract Near‐infrared (NIR)‐II fluorescence imaging‐guided photothermal therapy (PTT) has attracted great research interest, and constructing donor‐acceptor (D‐A) electronic configurations has become an established approach to lower bandgap and realize NIR‐II emission. However, very few π‐conjugated phototheranostic agents can realize efficient NIR‐II guided PTT using a clinically safe laser power density, implying that sufficient photothermal performance is still desired. In addition to the continuously refreshed photothermal conversion efficiency levels, the strategies that focus on enhancing light absorptivity have been rarely discussed and endow a new direction for enhancing PTT. Herein, a dimerization π‐extension strategy is raised to synthesize π‐conjugated dimers with A‐D‐A monomers. We observe that the light absorptivity (ε) of the dimers is strengthened three times owing to the enhanced electronic coupling effect as a result of the π‐conjugation extension, thereby surpassing the 2‐fold increase in chromophore numbers from the monomer to dimers. Thanks to the enhancement in light absorption, the dimers could generate much more photothermal heat than the monomer in in vivo PTT treatments. Therefore, an efficient anti‐tumor outcome has been fulfilled by using dimers under a low laser power (0.3 W/cm2). Moreover, the dimers with extended π‐conjugation structures become more favorable to the radiative excited state decay, thus exhibiting a distinguishing improvement in NIR‐II imaging compared with monomer. Collectively, due to the improved light absorptivity, the dimers can gain superior NIR‐II fluorescence brightness and photothermal performance over the recently reported material, which goes beyond the monomer in double doses for in vivo applications. All these results prove that dimerization is an effective strategy for designing high‐performance phototheranostic materials.

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.

BackgroundPheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than 1% -2%. In recent years, other rare mutations have gradually been discovered to be possibly related to the pathogenesis and metastasis of pheochromocytoma. Most patients with pheochromocytoma experience common symptoms like headaches, palpitations, and sweating, while some may have less common symptoms. The diversity of symptoms, genetic mutations, and limited treatment options make management challenging.Case presentationA 53-year-old woman was hospitalized after experiencing episodic epigastric pain for one month. A mass was found in her right adrenal gland and she underwent robot-assisted laparoscopic surgery, revealing a pheochromocytoma. At the 16-month follow-up, multiple metastatic lesions consistent with metastatic pheochromocytoma were found. A germline mutation in the dihydrolipoamide succinyltransferase (DLST) gene (c.330 + 14A>G) was detected, and despite trying chemotherapy and adjuvant therapy, the patient had a limited response with an overall survival of 27 months.ConclusionsDLST mutation is one of the rare pheochromocytoma-related mutated genes, and genetic sequencing is crucial for effective clinical management.

Abstract Aim To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. Methods From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. Results Of the 148 patients, 78 were in the chemoresistance group and 70 in the non‐chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19‐9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p 3 cm). Conclusions Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

BackgroundEvidence indicates that the addition of ezetimibe to statin therapy reduces cardiovascular events. However, the impact of ezetimibe–statin combination therapy on coronary plaque regression, plaque stabilization, and diameter stenosis remains a matter of controversy.MethodsWe performed electronic searches in PubMed, Web of Knowledge, and the Cochrane Central Register of Controlled Trials to identify eligible trials assessing the effects of ezetimibe–statin combination therapy versus statin monotherapy reporting at least one outcome among total atheroma volume (TAV), minimum fibrous cap thickness (FCT), lumen volume (LV), and lumen area (LA) derived from intravascular imaging modalities of intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We used the random-effects model and performed trial sequential analysis (TSA) during this meta-analysis.ResultsEleven articles with a total of 926 individuals (460 in the dual-lipid-lowering therapy group and 466 in the statin monotherapy group) were included in the final meta-analysis. Compared to statin monotherapy, ezetimibe–statin combination therapy was associated with significantly decreased TAV [WMD = −3.17, 95% CI (−5.42 to −0.92), and p = 0.006], with no effect on the LV of the coronary artery [WMD = −0.52, 95% CI (−2.24 to 1.21), and p = 0.56], the LA of the coronary artery [WMD = 0.16, 95% CI (−0.10–0.42), and p = 0.22], or minimum FCT thickness [WMD = 19.11, 95%CI (−12.76–50.97)].ConclusionIn patients with coronary artery disease, ezetimibe–statin combination therapy resulted in a significant regression in TAV compared to statin monotherapy, whereas no overall improvements of minimum FCT or lumenal stenosis were observed.

Abstract Aim To investigate the relationship among emotional intelligence (EI), resilience and academic procrastination (AP), and provide suggestions for the development of targeted intervention strategies and lowering of AP level of nursing undergraduates. Design A cross‐sectional study. Methods Three provincial universities offering nursing courses in China were investigated in this study. A convenience sample of 256 nursing undergraduates from May 2021 to September 2021 were recruited, with a response rate of 91.4%. Data were collected using face‐to‐face interviews. The survey tools included the General Information Questionnaire, Academic Procrastination Scale, Emotional Intelligence Scale and Resilience Scale. IBM SPSS v19.0 and Amos 22.0 were used for data analysis. Results The AP of sampled nursing undergraduates was at the middle level (54.4 ± 21.5). The AP of nursing undergraduates was negatively correlated with EI and resilience. Moreover, the analysis on the mediating role of resilience via structural equation model showed a good fit, with χ2/df = 2.34, RMSEA = 0.07, CFI = 0.99, GFI = 0.95, TLI = 0.98. Patient or Public Contribution No patient or public contribution.

Abstract Background Combination of chidamide and anti‐PD‐L1 inhibitor produce synergistic anti‐tumor effect in advanced NSCLC patients resistant to anti‐PD‐1 treatment. However, the effect of chidamide plus envafolimab has not been reported. Aims This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti‐PD‐1 treatment. Materials and Methods Eligible advanced NSCLC patients after resistant to anti‐PD‐1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression‐free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD‐L1, and blood TMB (bTMB) was also analyzed. Results After a median follow‐up of 8.1 (range: 7.6–9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9–5.5) months. Biomarker analysis revealed that patients with high‐level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD‐L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low‐level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. Discussion High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD‐L1 and low‐level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. Conclusion Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.