Association between increased systemic immune-inflammation index and postoperative delirium in older intertrochanteric fracture patients.

BACKGROUND AND PURPOSE: The systemic immune-inflammation index (SII), a novel inflammation index derived from the counts of circulating platelets, neutrophils and lymphocytes, has been studied in the treatment of acute cancer and ischemic stroke (AIS). However, the clinical value of the SII in postoperative delirium patients has not been further investigated. The purpose of our research was to study the incidence and preoperative risk factors for postoperative delirium (POD) and verify whether the SII could serve as a potential marker for POD in older intertrochanteric fracture patients. Finally, we created a novel nomogram for predicting POD in older patients with intertrochanteric fractures. METHODS: We enrolled elderly patients with intertrochanteric fractures who underwent proximal femoral nail antirotation (PFNA) between February 2021 and April 2023. Univariate and multivariate logistic analyses were subsequently performed to confirm the risk factors and construct a nomogram model.Calibration curve and clinical decision curve analysis (DCA) were used to assess the model's fitting performance. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility. RESULTS: A total of 293 patients were eligible for inclusion in the study, 25.6% (75/293) of whom had POD. The POD patients had higher SII values than the non-POD patients. The SII was strongly correlated with POD in older intertrochanteric fracture patients, and the optimal cutoff value was 752.6 × 109. Multivariate analysis revealed that age, diabetes, total albumin, SII > 752.6 × 109 and a CRP > 20.25 mg/L were independent risk factors for POD patients. By incorporating these 5 factors, the model achieved a concordance index of 0.745 (95% CI, 0.683-0.808) and had a well-fitted calibration curve and good clinical application value. CONCLUSION: The SII is a simple and valuable biomarker for POD, and the new nomogram model can be used to accurately predict the occurrence of POD. They can be utilized in clinical practice to identify those at high risk of POD in older intertrochanteric fracture patients.

LSPR sensing for in situ monitoring the Ag dissolution of Au@Ag core-shell nanoparticles in biological environments.

Silver nanoparticles (AgNPs) are extensively used as an antibacterial agent, and monitoring the dissolution behavior of AgNPs in native biological environments is critical in both optimizing their performance and regulating their safety. However, current assessment methods rely on sophisticated analytical tools that are off-site and time-consuming with potential underestimations, due to complicated sample preparation. Although localized surface plasmon resonance (LSPR) sensing offers a facile method for the detection of AgNP dissolution, it is limited by low sensitivity and poor nanoparticle stability in native biological environments. Herein, we constructed a highly sensitive and stable LSPR sensor using gold-silver core-shell nanoparticles (Au@AgNPs), in combination with polymeric stabilizing agents, for the direct measurement of the Ag shell dissolution in native biological media. The high sensitivity was attributed to the acute and large LSPR shift generated by bimetallic nanoparticles. The sensor was used for the real-time monitoring of the Ag dissolution of Au@AgNPs during their co-culture with both bacteria and fibroblast cells. The media pH was found to dominate the Ag dissolution process, where Au@AgNPs exhibited bactericidal effects in the bacteria environment with relatively low pH, but they showed little toxicity towards fibroblast cells at pH 7.4. The minimum inhibition concentration of Au@AgNPs for bacterial growth was found similar to that of AgNO3 in terms of released Ag amount. Thus, stabilized Au@AgNPs not only allow the in-situ monitoring of Ag dissolution via LSPR sensing but also constitute an effective antibacterial agent with controlled toxicity, holding great potential for future biomedical and healthcare applications.

Autoclavable Albumin-Based Cryogels with Uncompromising Properties.

The development of autoclavable hydrogels has been driven by the need for materials that can withstand the rigors of sterilization without compromising their properties or functionality. Many conventional hydrogels cannot withstand autoclave treatment owing to the breakdown of their composition or structure under the high-temperature and high-pressure environment of autoclaving. Here, the effect of autoclaving on the physical, mechanical, and biological properties of bovine serum albumin methacryloyl (BSAMA) cryogels at three protein concentrations (3, 5, and 10%) was extensively studied. We found that BSAMA cryogels at three concentrations remained little changed after autoclaving in terms of gross shape, pore structure, and protein secondary structure. Young's modulus of autoclaved BSAMA cryogels (BSAMAA) at low concentrations (3 and 5%) was similar to that of BSAMA cryogels, whereas 10% BSAMAA exhibited a higher Young's modulus value, compared with 10% BSAMA. Interestingly, BSAMAA cryogels prolonged degradation. Importantly, cell viability, drug release, and hemolytic behaviors were found to be similar among the pre- and post-autoclaved cryogels. Above all, autoclaving proved to be more effective in sterilizing BSAMA cryogels from bacteria contamination than UV and ethanol treatments. Thus, autoclavable BSAMA cryogels with uncompromising properties would be useful for biomedical applications.

An Engineered Protein-Based Building Block (Albumin Methacryloyl) for Fabrication of a 3D In Vitro Cryogel Model.

Drug-induced liver injury (DILI) is a leading cause of attrition in drug development or withdrawal; current animal experiments and traditional 2D cell culture systems fail to precisely predict the liver toxicity of drug candidates. Hence, there is an urgent need for an alternative in vitro model that can mimic the liver microenvironments and accurately detect human-specific drug hepatotoxicity. Here, for the first time we propose the fabrication of an albumin methacryloyl cryogel platform inspired by the liver's microarchitecture via emulating the mechanical properties and extracellular matrix (ECM) cues of liver. Engineered crosslinkable albumin methacryloyl is used as a protein-based building block for fabrication of albumin cryogel in vitro models that can have potential applications in 3D cell culture and drug screening. In this work, protein modification, cryogelation, and liver ECM coating were employed to engineer highly porous three-dimensional cryogels with high interconnectivity, liver-like stiffness, and liver ECM as artificial liver constructs. The resulting albumin-based cryogel in vitro model provided improved cell-cell and cell-material interactions and consequently displayed excellent liver functional gene expression, being conducive to detection of fialuridine (FIAU) hepatotoxicity.

4-Methoxydalbergione is a potent inhibitor of human astroglioma U87 cells in vitro and in vivo.

Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4-Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.

Highly substituted decoupled gelatin methacrylamide free of hydrolabile methacrylate impurities: An optimum choice for long-term stability and cytocompatibility.

Gelatin methacryloyl (GelMA; GM) contains impurities, including hydrolabile photosensitive methacrylate groups or soluble methacrylic acid (MA), which could be potentially detrimental to its in vitro and in vivo applications. To date, the influence of GM photocurable side chains on the cytotoxicity and ambient structural stability has remained to be investigated. Here, we successfully separated highly substituted decoupled gelatin methacrylamide (DGM) from GM via removing methacrylate impurities in order to evaluate its stability, cell viability, and cell toxicity, compared to GM, DGM plus soluble MA, and soluble MA. The photocurable methacrylate groups in GM were hydrolytically labile in neutral solutions, changing into soluble MA over time; on the other hand, the photocurable methacrylamide groups in DGM remained intact under the same conditions. Soluble MA was found to decrease cell viability in a dose dependent manner and caused severe cell toxicity at above 10 mg/mL. DGM plus MA started to impair cell viability at a 25 mg/mL concentration. DGM exhibited excellent cell viability and little cell toxicity across the treated concentrations (0.1-25 mg/mL). DGM without hydrolabile methacrylate and cytotoxic MA impurities could be a better choice for long term stability and good cell compatibility for bioapplications including bioprinting and cell encapsulation.

A core-scale reconstructing method for shale.

Characterization of shale cores with low and anisotropic permeability is complicated, due to the presence of multiscale pore structure and thin layers, and defies conventional methods. To accurately reproduce the morphology of multiscale pore structure of the shale core, a novel core-scale reconstructing method is proposed to reconstruct 3D digital-experimental models by means of the combination of SEM, EDS images, nitrogen adsorption and pressure pulse decay experiment result. In this method, the multiscale and multicomponent reconstructing algorithm is introduced to build the representative multiscale model for each layer, which can describe the complex 3D structures of nano organic pores, micro-nano inorganic pores, micro slits and several typical minerals. Especially, to reproduce the realistic morphology for shale, the optimization algorithm based on simulated annealing algorithm uses the experimental data as constrain conditions to adjust and optimize the model for each layer. To describe the bedding characteristics of the shale core, bedding fractures are constructed by analysis of the mineral distribution in the interface of two layers, and then the representative models for different layers are integrated together to obtain the final core-scale digital-experimental model. Finally, the model is validated by computing its morphological and flow properties and comparing them with those of the actual 3D shale sample. This method provide a way for systematically and continuously describe the multiscale and anisotropic pore structure (from nm-cm) of the shale core, and will be helpful for understanding the quality of the shale reservoir.

A two-angle model of dynamic wetting in microscale capillaries under low capillary numbers with experiments.

OBJECTIVES: An accurate model of the dynamic contact angle θd is critical for the calculation of capillary force in applications like enhanced oil recovery, where the capillary number Ca ranges from 10-10 to 10-5 and the Bond number Bo is less than 10-4. The rate-dependence of the dynamic contact angle under such conditions remains blurred, and is the main target of this study. EXPERIMENTS: Featuring with pressure control and interface tracking, the innovative experimental system presented in this work achieves the desired ranges of Ca and Bo, and enables the direct optical measurement of dynamic contact angles in capillaries as tiny as 40 × 20 (width × height) µm and 80 × 20 µm. The advancing and receding processes of wetting and nonwetting liquids were tested. FINDINGS: The dynamic contact angle was confirmed velocity-independent with 10-9 < Ca < 10-5 (contact line velocity V = 0.135-490 µm/s) and it can be described by a two-angle model with desirable accuracy. A modified two-angle model was developed and an empirical form was obtained from experiments. For different liquids contacting the same surface, the advancing angle θadv approximately equals the static contact angle θo. The receding angle θrec was found to be a linear function of θadv, in good agreement with our and other experiments from the literature.

Preparation and in vitro evaluation of strontium-doped calcium silicate/gypsum bioactive bone cement.

The combination of two or more bioactive components with different biodegradability could cooperatively improve the physicochemical and biological performances of the biomaterials. Here we explore the use of α-calcium sulfate hemihydrate (α-CSH) and calcium silicate with and without strontium doping (Sr-CSi, CSi) to fabricate new bioactive cements with appropriate biodegradability as bone implants. The cements were fabricated by adding different amounts (0-35 wt%) of Sr-CSi (or CSi) into the α-CSH-based pastes at a liquid-to-solid ratio of 0.4. The addition of Sr-CSi into α-CSH cements not only led to a pH rise in the immersion medium, but also changed the surface reactivity of cements, making them more bioactive and therefore promoting apatite mineralization in simulated body fluid (SBF). The impact of additives on long-term in vitro degradation was evaluated by soaking the cements in Tris buffer, SBF, and α-minimal essential medium (α-MEM) for a period of five weeks. An addition of 20% Sr-CSi to α-CSH cement retarded the weight loss of the samples to 36% (in Tris buffer), 43% (in SBF) and 54% (in α-MEM) as compared with the pure α-CSH cement. However, the addition of CSi resulted in a slightly faster degradation in comparison with Sr-CSi in these media. Finally, the in vitro cell-ion dissolution products interaction study using human fetal osteoblast cells demonstrated that the addition of Sr-CSi improved cell viability and proliferation. These results indicate that tailorable bioactivity and biodegradation behavior can be achieved in gypsum cement by adding Sr-CSi, and such biocements will be of benefit for enhancing bone defect repair.

Analysis of risk factors of hemorrhagic transformation after acute ischemic stroke: cerebral microbleeds do not correlate with hemorrhagic transformation.

To study the potential risk factors including cerebral microbleeds (CMB) of hemorrhagic transformation (HT) after acute ischemic stroke. We included 348 consecutive patients with acute infarction who were hospitalized in two centers from June 2009 to December 2010. Acute ischemic infarctions were subdivided into atherosclerotic, cardioemblic, lacunar, and undetermined infarction groups. The related risk factors were recruited for analysis. All patients underwent gradient-echo T2-weighted imaging (GRE) to detect CMB and HT. Logistic regression analysis was used to analyze relationships, with HT as response variable and potential risk factors as explanatory variables. Multivariate logistic regression analysis demonstrated that predictor factors of HT were cardioembolic infarction (OR 24.956, 95 % CI 2.734-227.801, P = 0.004), infarction of undetermined causes (OR 19.381, 95 % CI 1.834-205.104, P = 0.014), and scores of NIHSS (OR 1.187, 95 % CI 1.109-1.292, P < 0.001), diabetes mellitus (OR 4.973, 95 % CI 2.004-12.338, P = 0.001). Whereas, the level of low-density lipoprotein was the protective factor (OR 0.654, 95 % CI 0.430-0.996, P = 0.048).The prevalence of CMB was 45.98 % (160/348) with no statistically difference among different subtypes. Thirty-five out of 348 (10.06 %) patients with ischemic stroke developed HT with a statistical difference among different subtypes of ischemia (χ (2) = 42.140, P < 0.001). The distributions of HI and PH among subgroups were variable with significant differences (χ (2) = 17.536, P = 0.001; χ (2) = 12.028, P = 0.007). PH frequency of cardioembolism was the highest (4/28, 14.29 %), and symptomatic ICH was also highest (7.14 %). The CMBs do not significantly correlate with HT. Knowledge of the risk factors associated with HT after ACI, especially HT following thrombolyitc therapy may provide insight into the mechanisms underlying the development of HT, helps to develop treatment strategy that reduces the risk of PH and implicates for the design of future acute ischemic stroke trials.

Novel highly bioactive and biodegradable gypsum/calcium silicate composite bone cements: from physicochemical characteristics to in vivo aspects.

Gypsum is a promising material for bone defect repair due to its osteoconductivity, whereas it is still limited in orthopedic and dental surgeries due to its low bioactivity and too rapid resorption so that one major concern is the significant loss in microstructural stability in vivo. In the present strategy some key features were significantly improved by introducing rapidly biodegradable but highly bioactive calcium silicate (CS) for regulating the physicochemical properties and biological performances of the gypsum-based cements at the same liquid/solid ratio. We demonstrated that introduction of 23% CS into ß-calcium sulfate hemihydrate (CSH) could improve the physicochemical properties but would not compromise the mechanical strength of the composite. The surface bioactivity was significantly enhanced by introducing 23% CS, and these biphasic composites were favorable for decelerating the biodegradation rate by nearly 18.5% in 28 days in vitro. A mild bioresorption rate, with 39.6% of composite residual 4 weeks after operation, was determined when implanted in subcutaneous tissue of rats. 8 weeks after implantation, the composite cement containing 23% CS significantly enhanced new bone tissue regeneration with a much higher relative bone content (∼68.6%) than pure gypsum in critical size femoral defects in rabbits. The novel CSH-CS biocements represent promising candidates for rapid bone resconstruction and repair in trauma and pathological conditions.

Biomimetic preparation of trace element-codoped calcium phosphate for promoting osteoporotic bone defect repair.

Specific implants to speedily regenerate critical-sized osteoporotic bone defects (COBDs) are a major clinical need. However, little progress in methods focusing on biological repair has been reported. We developed a biomimetic mineralization method to prepare trace element-codoped calcium phosphate (CaP) particles via hydrothermal treatment of modified simulated body fluid (SBF) with the addition of binary to quaternary trace elements. The morphology, structure, and composition of the particles were characterized by a combination of SEM, TEM, XRD, and FTIR measurements. The quantitative analysis shows that the dopant contents in the solid phase can be regulated by the trace ion concentrations in the aqueous medium. The conditioned cell culture medium from the quaternary Mg/Zn/Sr/Si-co-doped CaP (qCaP) could significantly enhance cell activity and osteogenic differentiation of ovariectomized rat-derived bone marrow mesenchymal stem cells. After injecting the qCaP-loaded chitosan/hyaluronic acid hydrogel into the COBDs, histology and computed tomography scanning revealed that the new bone regeneration was significantly enhanced, and the quantity of mature bone was substantially increased in the rats implanted with qCaP 12 weeks post-operatively in comparison with the defects filled with the CaP obtained from SBF. These results suggest that the biomimetic mineralization of the trace ion-added SBF allows the preparation of highly bioactive trace element-codoped CaP biomaterials and these materials are potential candidates for the biological repair of COBDs.

[Effect of IGF-1 on NO and PGE2 in rabbit articular chondrocytes induced by IL-1].

OBJECTIVE: To explore the effect of insulin-like growth factor (IGF-1) on the concentration of NO and PGE(2) in the supernatant of rabbit articular chondrocytes induced by IL-1, and to explore the mechanism of IGF-1 in the development of osteoarthritis (OA). METHODS: The samples were divided into 7 groups: IL-1beta 10 microg/L group, IL-1beta 10 microg/L+IGF-1 1 microg/L group, IL-1beta 10 microg/L+IGF-1 10 microg/L group, IL-1beta 10 microg/L+IGF-1 50 microg/L group, IL-1beta 10 microg/L+IGF-1 100 microg/L group, IGF-1 50 microg/L group, and a blank control group. The chondrocytes from the articular cartilage of 2 month old rabbits were cultivated and identified, and then co-cultured in the second filial generation chondrocytes on plates with or without recombinant human IGF-1 or IL-1. The concentration of NO was detected by nitrate reductase kit, and that of PGE(2) by enzyme-linked immunosorbent assay (ELISA). The results were analyzed by statistical method. RESULTS: The average value of NO and PGE(2) was (89.971+/-10.224) micromol/L and (22.028+/-8.731) micromol/L in the IL-1beta 10 microg/L group, and (12.404+/-8.809) micromol/L and (1.900+/-0.227) ng/L in the blank control group. The concentration of NO and PGE(2) in IL-1beta 10 microg/L group was significantly higher than that in the blank control group (P<0.05). At the same concentration of 10 microg/L, IGF-1 could dose-dependently decrease the increase of NO and PGE(2) concentration induced by IL-1beta in the chondrocytes supernatant in vitro, and the optimum concentration of IGF-1 was 50 microg/L. CONCLUSION: IL-1 can significantly increase the concentration of NO and PGE(2), and IGF-1 can dose-dependently decrease the concentration of NO and PGE(2) in the chondrocytes supernatant in vitro. The optimum concentration of IGF-1 was 50 microg/L.

[Culture of chondrocytes using nano-hydroxyapatite/collagen in vitro].

OBJECTIVE: To evaluate the value of the nano-hydroxyapatite/ collagen (nHAC) as a scaffold for cartilage tissue engineering. METHODS: The normal cartilage from patients after total hip arthroplasty of osteoarthritis was selected, and then chondrocytes were digested, separated, and amplificate in vitro. The chondrocytes were seeded onto the nHAC scaffold and were cultured in a 3-dimensional environment for 5 and 10 days. The effects of the composite scaffold on the cell adhesion, proliferation, morphological changes, and synthesis of the extracellular matrix were observed by scanning electronic microscopy and immunohistochemistry. RESULTS: The chondrocytes could adhere to the surface of the scaffolds, proliferate, and migrate into the scaffolds. They maintained round and could secrete extracellular matrix on the porous scaffold. CONCLUSION: The nHAC can be used as the cartilage cell carrier.

[Herceptin plus adjuvant chemotherapy for the prognosis of patients with human epithelial growth factor receptor 2 positive early-stage breast cancer: a meta-analysis].

OBJECTIVE: To evaluate the effect of herceptin(trastuzumab) plus adjuvant chemotherapy on the prognosis of patients with human epithelial growth factor receptor 2 (HER2) positive early-stage breast cancer by Meta-analysis. METHODS: Search all of randomized clinical trials (RCTs) on herceptin plus adjuvant chemotherapy for HER2 positive early-stage breast cancer in MEDLINE, EMBase, Cochrane library, Clinical Trails, ASCO Conference data, CHKD, Wanfang Database, VIP information, scholar.google.com and SIGLE. A Meta-analysis was carried out by collecting information based on the inclusion and exclusion criteria from all papers available. RESULTS: The Meta-analysis included 4 trials. A total of 9116 patients were included in the analysis(4555 in the study group and 4561 in the control group). There were statistical differences between the study group(herceptin plus adjuvant chemotherapy) and the control group(adjuvant chemotherapy) in the disease-free survival rate [relative risk(RR)=1.08, 95% CI, 1.06-1.09, P<0.001], the overall survival rate(RR=1.01, 95% CI, 1.01-1.02, P=0.0003), the distant recurrence rate(RR=0.49, 95% CI, 0.42-0.57, P<0.001), and the cardiac events rate (RR=3.93,95% CI, 1.03-15.06, P=0.05). CONCLUSION: Herceptin plus adjuvant chemotherapy can improve the disease-free survival rate and the overall survival rate, decrease distant recurrence rate of patients with HER2 positive early-stage breast cancer, but may cause heart toxicity, especially when combined with anthracycline (doxorubicin).