Surgical treatment outcomes of acetabular posterior wall and posterior column fractures using 3D printing technology and individualized custom-made metal plates: a retrospective study.

BACKGROUND: Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures. METHODS: A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods). Surgical and instrument operation times, intraoperative fluoroscopy frequency, intraoperative blood loss, fracture reduction quality, fracture healing time, preoperative and 12-month postoperative pain scores (Numeric Rating Scale, NRS), hip joint function at 6 and 12 months (Harris scores), and complications were compared. RESULTS: The surgical and instrument operation times were significantly shorter in the 3D printing group (p < 0.001). The 3D printing group exhibited significantly lower intraoperative fluoroscopy frequency and blood loss (p = 0.001 and p < 0.001, respectively). No significant differences were observed between the two groups in terms of fracture reduction quality, fracture healing time, preoperative pain scores (NRS scores), and 6-month hip joint function (Harris scores) (p > 0.05). However, at 12 months, hip joint function and pain scores were significantly better in the 3D printing group (p < 0.05). Although the incidence of complications was lower in the 3D printing group (18.8% vs. 33.3%), the difference did not reach statistical significance (p = 0.433). CONCLUSION: Combining 3D printing with individualized custom-made metal plates for acetabular posterior wall and column fractures reduces surgery and instrument time, minimizes intraoperative procedures and blood loss, enhancing long-term hip joint function recovery. CLINICAL TRIAL REGISTRATION: 12/04/2023;Trial Registration No. ChiCTR2300070438; http://www.chictr.org.cn .

Exploration of shared gene signatures and molecular mechanisms between type 2 diabetes and osteoporosis.

Type 2 diabetes mellitus (T2D) and osteoporosis (OP) are systemic metabolic diseases and often coexist. The mechanism underlying this interrelationship remains unclear. We downloaded microarray data for T2D and OP from the Gene Expression Omnibus (GEO) database. Using weighted gene co-expression network analysis (WGCNA), we identified co-expression modules linked to both T2D and OP. To further investigate the functional implications of these associated genes, we evaluated enrichment using ClueGO software. Additionally, we performed a biological process analysis of the genes unique in T2D and OP. We constructed a comprehensive miRNA-mRNA network by incorporating target genes and overlapping genes from the shared pool. Through the implementation of WGCNA, we successfully identified four modules that propose a plausible model that elucidates the disease pathway based on the associated and distinct gene profiles of T2D and OP. The miRNA-mRNA network analysis revealed co-expression of PDIA6 and SLC16A1; their expression was upregulated in patients with T2D and islet ß-cell lines. Remarkably, PDIA6 and SLC16A1 were observed to inhibit the proliferation of pancreatic ß cells and promote apoptosis in vitro, while downregulation of PDIA6 and SLC16A1 expression led to enhanced insulin secretion. This is the first study to reveal the significant roles of PDIA6 and SLC16A1 in the pathogenesis of T2D and OP, thereby identifying additional genes that hold potential as indicators or targets for therapy.

Creep-type all-solid-state cathode achieving long life.

Electrochemical-mechanical coupling poses enormous challenges to the interfacial and structural stability but create new opportunities to design innovative all-solid-state batteries from scratch. Relying on the solid-solid constraint in the space-limited domain structure, we propose to exploit the lithiation-induced stress to drive the active materials creep, thereby improving the structural integrity. For demonstration, we fabricate the creep-type all-solid-state cathode using creepable Se material and an all-in-one rigid ionic/electronic conducting Mo6Se8 framework. As indicated by the in-situ experiment and numerical simulation, this cathode presents unique capabilities in improving interparticle contact and avoiding particle fracture, leading to its superior electrochemical performance, including a superior long-cycle life of more than 3000 cycles at 0.5 C and a high volumetric energy density of 2460 Wh/L at the cathode level. We believe this innovative strategy to utilize mechanics to boost the electrochemical performance could shed light on the future design of all-solid-state batteries for practical applications.

Vapor/Vapor-Solid Interfacial Growth of Covalent Organic Framework Membranes on Alumina Hollow Fiber for Advanced Molecular Separation.

Covalent organic frameworks (COFs), known for their chemical stability and porous crystalline structure, hold promises as advanced separation membranes. However, fabricating high-quality COF membranes, particularly on industrial-preferred hollow fiber substrates, remains challenging. This study introduces a novel vapor/vapor-solid (V/V-S) method for growing ultrathin crystalline TpPa-1 COF membranes on the inner lumen surface of alumina hollow fibers (TpPa-1/Alumina). Through vapor-phase monomer introduction onto polydopamine-modified alumina at 170 °C and 1 atm, efficient polymerization and crystallization occur at the confined V-S interface. This enables one-step growth within 8 h, producing 100 nm thick COF membranes with strong substrate adhesion. TpPa-1/Alumina exhibits exceptional stability and performance over 80 h in continuous cross-flow organic solvent nanofiltration (OSN), with methanol permeance of about 200 L m-2 h-1 bar-1 and dye rejection with molecular weight cutoff (MWCO) of approximately 700 Da. Moreover, the versatile V/V-S method synthesizes two additional COF membranes (TpPa2Cl/Alumina and TpHz/Alumina) with different pore sizes and chemical environments. Adjusting the COF membrane thickness between 100-500 nm is achievable easily by varying the growth cycle numbers. Notably, TpPa2Cl/Alumina demonstrates excellent OSN performance in separating the model active pharmaceutical ingredient glycyrrhizic acid (GA) from dimethyl sulfoxide (DMSO), highlighting the method's potential for large-scale industrial applications.

FLT3-selective PROTAC: Enhanced safety and increased synergy with Venetoclax in FLT3-ITD mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) patients carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis. While some FLT3 inhibitors have been used clinically, challenges such as short efficacy and poor specificity persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher and rapid targeting capability. Gilteritinib, used as the ligand for the target protein, was connected with different E3 ligase ligands to synthesize several series of PROTAC targeting FLT3-ITD. Through screening and structural optimization, the optimal lead compound PROTAC Z29 showed better specificity than Gilteritinib. Z29 induced FLT3 degradation through the proteasome pathway and inhibited tumor growth in subcutaneous xenograft mice. We verified Z29's minimal impact on platelets in a patient-derived xenografts (PDX) model compared to Gilteritinib. The combination of Z29 and Venetoclax showed better anti-tumor effects, lower platelet toxicity, and lower hepatic toxicity in FLT3-ITD+ models. The FLT3-selective PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy with Venetoclax. It is a promising strategy for FLT3-ITD+ patients, especially those with platelet deficiency or liver damage.

Embedded Bioprinting of Tissue-like Structures Using κ-Carrageenan Sub-Microgel Medium.

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.

Enhancing the nonlinear rheological property and digestibility of mung bean flour gels using controlled microwave treatments: Effect of starch debranching and protein denaturation.

In this study, we examined the possibility of using industrial microwave processing to enhance the gelling properties and reduce the starch digestibility of mung bean flour (MBF). MBF (12.6 % moisture) was microwaved at a power of 6 W/g to different final temperatures (100-130 °C), and then its structural and functional properties were characterized. The microwave treatment had little impact on the crystalline structure or amylose content of the starch, but it roughened the starch granule surfaces and decreased the short-range ordered structure and degree of branching. In addition, the extent of mung bean protein denaturation caused by the microwave treatment depended on the final temperature. Slightly denaturing the proteins (100 °C) did not affect the nature of the gels (protein phase dispersed in a starch phase) but the gel network became more compact. Moderately denaturing the proteins (110-120 °C) led to more compact and homogeneous starch-protein double network gels. Excessive protein denaturation (130 °C) caused the gel structure to become more heterogeneous. As a result, the facilitated tangles between starch chains by more linear starch molecules after debranching, and the protein network produced by moderate protein denaturation led to the formation of stronger gel and the improvement of plasticity during large deformation (large amplitude oscillatory shear-LAOS). Starch recrystallization, lipid complexion, and protein network retard starch digestion in the MBF gels. In conclusion, an industrial microwave treatment improved the gelling and digestive properties of MBF, and Lissajous curve has good adaptability in characterizing the viscoelasticity of gels under large deformations.

DCPIB Attenuates Ischemia-Reperfusion Injury by Regulating Microglial M1/M2 Polarization and Oxidative Stress.

The inflammatory response plays an indispensable role in ischemia-reperfusion injury, the most significant of which is the inflammatory response caused by microglial polarization. Anti-inflammatory therapy is also an important remedial measure after failed vascular reconstruction. Maintaining the internal homeostasis of the brain is a crucial measure for suppressing the inflammatory response. The mechanism underlying the relationship between DCPIB, a selective blocker of volume-regulated anion channels (VRAC), and inflammation induced by cerebral ischemia-reperfusion injury is currently unclear. The purpose of this study was to investigate the relationship between DCPIB and microglial M1/M2 polarization-mediated inflammation after cerebral ischemia-reperfusion injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). DCPIB was administered by a lateral ventricular injection within 5 min after reperfusion. Behavioral assessments were conducted at 1, 3, and 7 days after tMCAO/R. Pathological injuries were evaluated using TTC assay, HE and Nissl staining, brain water content measurement, and immunofluorescence staining. The levels of inflammatory cytokines were analyzed using qPCR and ELISA. Additionally, the phenotypic variations of microglia were examined using immunofluorescence staining. In mouse tMCAO/R model, DCPIB administration markably reduced mortality, improved behavioral performance, and alleviated pathological injury. DCPIB treatment significantly inhibited the inflammatory response, promoted the conversion of M1 microglia to M2 microglia via the MAPK signaling pathway, and ultimately protected neurons from the microglia-mediated inflammatory response. In addition, DCPIB inhibited oxidative stress induced by cerebral ischemia-reperfusion injury. In conclusion, DCPIB attenuates cerebral ischemia-reperfusion injury by regulating microglial M1/M2 polarization and oxidative stress.

Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated. RESULTS: GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.

Roles of long noncoding RNAs in human inflammatory diseases.

Chemokines, cytokines, and inflammatory cells mediate the onset and progression of many diseases through the induction of an inflammatory response. LncRNAs have emerged as important regulators of gene expression and signaling pathways. Increasing evidence suggests that lncRNAs are key players in the inflammatory response, making it a potential therapeutic target for various diseases. From the perspective of lncRNAs and inflammatory factors, we summarized the expression level and regulatory mechanisms of lncRNAs in human inflammatory diseases, such as cardiovascular disease, osteoarthritis, sepsis, chronic obstructive pulmonary disease, asthma, acute lung injury, diabetic retinopathy, and Parkinson's disease. We also summarized the functions of lncRNAs in the macrophages polarization and discussed the potential applications of lncRNAs in human inflammatory diseases. Although our understanding of lncRNAs is still in its infancy, these data will provide a theoretical basis for the clinical application of lncRNAs.

Development, validation and reliability testing of the hospice care environment scale.

BACKGROUND: WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. METHODS: Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. RESULT: The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach's α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach's α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. CONCLUSION: The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment.

Pre- and postpartum fear of childbirth and its predictors among rural women in China.

BACKGROUND: Fear of childbirth (FOC) can influence both maternal and child health. Research on FOC in China is scarce, especially on rural women. This study aimed to assess pre- and postpartum FOC and its predictors among Chinese rural women. METHODS: This was a prospective correlation study. A total of 569 women completed the prenatal questionnaire in the third trimester, and 477 of them completed the postpartum questionnaire within three days after childbirth. Maternal socio-demographic information, clinical information, childbirth self-efficacy and prenatal and postpartum FOC were investigated. FOC was evaluated using the Wijma Childbirth Expectancy/ Experience Questionnaire (WDEQ). Descriptive, bivariate, multivariate linear regression analysis, univariate and multivariate logistic regression analyses were performed. RESULTS: The mean pre- and postpartum FOC scores were 64.5 (standard deviation: 25.1) and 64.3 (standard deviation: 23.9), respectively, with 20.8% of women reporting severe fear before childbirth and 18.2% after childbirth. Multivariate linear regression analysis revealed predictors for higher levels of prenatal FOC including higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy (p < 0.05) and the predictors for higher levels of postpartum FOC included unemployed status, lower childbirth self-efficacy, and higher prenatal FOC (p < 0.05). Multivariate logistic regression showed that higher childbirth self-efficacy reduced the likelihood of severe prenatal FOC (OR: 0.99, p < 0.001), while severe prenatal FOC increased the likelihood of severe postpartum FOC (OR: 3.57, p < 0.001). CONCLUSION: The rural women have high levels of FOC before and after childbirth, with approximately 20% experiencing severe FOC during both periods. Higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy are predictors of heightened prenatal FOC. Unemployed status, lower childbirth self-efficacy, and higher prenatal FOC are predictors of heightened postpartum FOC. Notably, enhancing childbirth self-efficacy emerges as crucial in mitigating severe prenatal FOC, while severe prenatal FOC significantly increases the likelihood of severe postpartum FOC. The development of targeted intervention strategies for the above factors can help reduce women's FOC level and improve their overall pregnancy and childbirth experience.

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population.

Alcohol use disorders are among the top causes of the global burden of disease, yet therapeutic interventions are limited. Reduced desire to drink in patients treated with semaglutide has raised interest regarding its potential therapeutic benefits for alcohol use disorders. In this retrospective cohort study of electronic health records of 83,825 patients with obesity, we show that semaglutide compared with other anti-obesity medications is associated with a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder for a 12-month follow-up period. Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without type 2 diabetes. Similar findings are replicated in the study population with 598,803 patients with type 2 diabetes. These findings provide evidence of the potential benefit of semaglutide in AUD in real-world populations and call for further randomized clinicl trials.

Early diagnostic value of ECT whole-body bone imaging combined with PINP and ß-CTX for bone metastasis of lung cancer.

OBJECTIVE: This research was aimed at investigating the early diagnostic value of emission computed tomograph (ECT) whole-body bone imaging combined with PINP and ß-CTX for bone metastasis of lung cancer. METHODS: Case data of 86 lung cancer patients were categorized into lung cancer with bone metastasis (LCWBM, 46 cases) and lung cancer without bone metastasis (LCWOBM, 40 cases) groups according to the presence or absence of bone metastasis. Patients' general information were collected. ECT whole-body bone imaging was used to detect bone metastases and the grading of the extent of disease (EOD) in both groups, and electrochemiluminescence was utilized to detect the serum levels of PINP and ß-CTX. Spearman correlation analysis was employed to evaluate the correlation between EOD grading and PINP and ß-CTX levels. Logistic univariate and multivariate regression was implemented to analyze the risk factors of bone metastasis of lung cancer. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic efficacy of the single test of ECT whole-body bone imaging, PINP, or ß-CTX and the combination of the three tests. RESULTS: The differences in pathological type, clinical stage and EOD grading, the number of positive ECT cases, and the expression levels of PINP and ß-CTX between the LCWBM and LCWOBM groups were statistically significant. In LCWBM patients with different EOD grading, the trends of the expression of PINP and ß-CTX were grade 3 > grade 2 > grade 1 and grade 0. Further correlation analyses revealed that EOD grading showed a significant positive correlation with the PINP and ß-CTX expression levels. Univariate logistic regression analysis demonstrated that adenocarcinoma, TNM stage IV, ECT positivity, and high expression of PINP and ß-CTX were associated with bone metastasis of lung cancer, and multivariate logistic regression analysis indicated that ECT positivity, high expression of PINP and ß-CTX were independent risk factors for bone metastasis of lung cancer. The area under the curve (AUC) of ECT, PINP, and ß-CTX alone for the diagnosis of bone metastasis of lung cancer were 0.872, 0.888, and 0.874, respectively, and the AUC for the combined diagnosis of the three was 0.963, which was greater than that of any one of the individual indices, with a sensitivity of 86.96% and a specificity of 97.50% at a Youden index of 0.845. CONCLUSION: ECT whole-body bone imaging combined with PINP and ß-CTX has high diagnostic value for bone metastasis of lung cancer.

Indocyanine green-mediated fabrication of urchin-like hydroxyethyl starch nanocarriers for enhanced drug tumor EPR and deep penetration effects.

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.

Co-delivery of fucoxanthin and Twist siRNA using hydroxyethyl starch-cholesterol self-assembled polymer nanoparticles for triple-negative breast cancer synergistic therapy.

INTRODUCTION: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. OBJECTIVES: Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. METHODS AND RESULTS: Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. CONCLUSION: Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.

Three-year follow-up of a novel orthopedic ward fracture liaison services (OWFLS) model.

OBJECTIVE: We established an orthopedic ward fracture liaison services (OWFLS) model and evaluated its role in improving detection rates of bone metabolic markers, treatment rates, and long-term treatability. METHODS: This observational retrospective cohort study included 120 patients aged >50 years hospitalized for primary osteoporotic fracture from January 2018 to January 2019 (group A: not included in OWFLS). Group B (included in OWFLS) comprised 120 patients from February 2019 to February 2020. We compared rates of bone metabolic index testing, treatment, and adherence; symptomatic improvement; and recurrent fracture between groups. RESULTS: Rates of bone metabolism index testing (50% vs. 0%) and medication use (94.2% vs. 64.2%) were significantly higher after OWFLS implementation. There was no significant difference in adherence rates at 3 months between groups (97.3% vs. 93.5%). Adherence rates at 1 and 3 years were better in group B than A (73.5% vs. 51.9%; 57.5% vs. 26%, respectively). Recurrence of bone pain at 1 and 3 years was significantly lower in group B than A (20.4% vs. 46.8%; 45.1% vs. 76.6%, respectively). CONCLUSIONS: OWFLS improved the detection rate of bone metabolism indicators, treatment rate, and patient adherence and reduced recurrence of bone pain. OWFLS may be suitable for settings lacking human resources.