Factors influencing recurrence and model development for recurrence of minimally invasive percutaneous transhepatic lithotripsy: a single-center retrospective study.

OBJECTIVE: To identify factors influencing recurrence after percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) and to develop a predictive model. METHODS: We retrospectively analyzed clinical data from 354 patients with intrahepatic and extrahepatic bile duct stones treated with PTCSL at Qinzhou First People's Hospital between February 2018 and January 2020. Patients were followed for three years and categorized into non-recurrence and recurrence groups based on postoperative outcome. Univariate analysis identified possible predictors of stone recurrence. Data were split using the gradient boosting machine (GBM) algorithm, assigning 70% as the training set and 30% as the test set. The predictive performance of the GBM model was assessed using the receiver operating characteristic (ROC) curve and calibration curve, and compared with a logistic regression model. RESULTS: Six factors were identified as significant predictors of recurrence: age, diabetes, total bilirubin, biliary stricture, number of stones, and stone diameter. The GBM model, developed based on these factors, showed high predictive accuracy. The area under the ROC curve (AUC) was 0.763 (95% CI: 0.695-0.830) for the training set and 0.709 (95% CI: 0.596-0.822) for the test set. Optimal cutoff values were 0.286 and 0.264, with sensitivities of 62.30% and 66.70%, and specificities of 77.20% and 68.50%, respectively. Calibration curves indicated good agreement between predicted probabilities and observed recurrence rates in both sets. DeLong's test revealed no significant differences between the GBM and logistic regression models in predictive performance (training set: D = 0.003, P = 0.997 > 0.05; test set: D = 0.075, P = 0.940 > 0.05). CONCLUSION: Biliary stricture, stone diameter, diabetes, stone number, age, and total bilirubin significantly influence stone recurrence after PTCSL. The GBM model, based on these factors, demonstrates robust accuracy and discrimination. Both GBM and logistic regression models effectively predicted stone recurrence post-PTCSL.

3D-Printed Composite Bioceramic Scaffolds for Bone and Cartilage Integrated Regeneration.

Osteoarthritis may result in both cartilage and subchondral bone damage. It is a significant challenge to simultaneously repair cartilage due to the distinct biological properties between cartilage and bone. Here, strontium copper tetrasilicate/ß-tricalcium phosphate (Wesselsite[SrCuSi4O10]/Ca3(PO4)2, WES-TCP) composite scaffolds with different WES contents (1, 2, and 4 wt %) were fabricated via a three-dimensional (3D) printing method for the osteochondral regeneration. The physicochemical properties and biological activities of the scaffolds were systematically investigated. 2WES-TCP (WES-TCP with 2 wt % WES) composite scaffolds not only improved the compressive strength but also enhanced the proliferation of both rabbit bone mesenchymal stem cells (rBMSCs) and chondrocytes, as well as their differentiation. The in vivo study further confirmed that WES-TCP scaffolds significantly promoted the regeneration of both bone and cartilage tissue in rabbit osteochondral defects compared with pure TCP scaffolds owing to the sustained and controlled release of bioactive ions (Si, Cu, and Sr) from bioactive scaffolds. These results show that 3D-printed WES-TCP scaffolds with bilineage bioactivities take full advantage of the bifunctional properties of bioceramics to reconstruct the complex osteochondral interface, which broadens the approach to engineering therapeutic platforms for biomedical applications.

3D-printed scaffold harboring copper ions combined with near-infrared irradiation for local therapy of cancer.

Cancer is a major health threat and a leading cause of human death worldwide. Surgical resection is the primary treatment for most cancers; however, some patients develop locoregional recurrence. Here, we developed an in situ cancer therapeutic system aimed to locally treat cancer and prevent postoperative recurrence. A functional scaffold, based on alginate/gelatin and crosslinked with copper ions, was fabricated by 3D printing and showed an excellent photothermal effect under near-infrared (NIR) irradiation. The combination of copper ions and NIR effectively killed thyroid cancer cells and patient-derived organoids, indicating a synergetic and broad-spectrum antitumor effect on thyroid cancer through the chemo-photothermal therapy. This implantable stent is designed to provide effective treatment in the vicinity of the tumor site and can be degraded without secondary surgery. The copper-loaded hydrogel scaffold may be a potential candidate for local cancer treatment and pave the way for precise and effective cancer therapy.

Three-Dimensional Printing Multi-Drug Delivery Core/Shell Fiber Systems with Designed Release Capability.

A hydrogel system with the ability to control the delivery of multiple drugs has gained increasing interest for localized disease treatment and tissue engineering applications. In this study, a triple-drug-loaded model based on a core/shell fiber system (CFS) was fabricated through the co-axial 3D printing of hydrogel inks. A CFS with drug 1 loaded in the core, drug 2 in the shell part, and drug 3 in the hollow channel of the CFS was printed on a rotating collector using a co-axial nozzle. Doxorubicin (DOX), as the model drug, was selected to load in the core, with the shell and channel part of the CFS represented as drugs 1, 2, and 3, respectively. Drug 2 achieved the fastest release, while drug 3 showed the slowest release, which indicated that the three types of drugs printed on the CFS spatially can achieve sequential triple-drug release. Moreover, the release rate and sustained duration of each drug could be controlled by the unique core/shell helical structure, the concentration of alginate gels, the cross-linking density, the size and number of the open orifices in the fibers, and the CFS. Additionally, a near-infrared (NIR) laser or pH-responsive drug release could also be realized by introducing photo-thermal materials or a pH-sensitive polymer into this system. Finally, the drug-loaded system showed effective localized cancer therapy in vitro and in vivo. Therefore, this prepared CFS showed the potential application for disease treatment and tissue engineering by sequential- or stimulus-responsively releasing multi-drugs.

Correlating the Valence State with the Adsorption Behavior of a Cu-Based Electrocatalyst for Furfural Oxidation with Anodic Hydrogen Production Reaction.

The low-potential furfural oxidation reaction (FFOR) on a Cu-based electrocatalyst can produce H2 at the anode, thereby providing a bipolar H2 production system with an ultralow cell voltage. However, the intrinsic activity and stability of the Cu-based electrocatalyst for the FFOR remain unsatisfactory for practical applications. This study investigates the correlation between the valence state and the adsorption behavior of the Cu-based electrocatalyst in furfural oxidation. Cu0 is the adsorption site with low intrinsic activity. Cu+ , which exists in the form of Cu(OH)ads in alkaline electrolytes, has no adsorption ability but can improve the performance of Cu0 by promoting the adsorption of FF. Moreover, a mixed-valence Cu-based electrocatalyst (MV Cu) with high intrinsic activity and stability is prepared electrochemically. With the MV Cu catalyst, the assembled dual-side H2 production electrolyzer has a low electricity requirement of only 0.24 kWh mH2 -3 at an ultralow cell voltage of 0.3 V, and it exhibits sufficient stability. This study not only correlates the valence state with the adsorption behavior of the Cu-based electrocatalyst for the low-potential FFOR with anodic H2 production but also reveals the mechanism of deactivation to provide design principles for Cu-based electrocatalysts with satisfactory stability.

3D printed hollow channeled hydrogel scaffolds with antibacterial and wound healing activities.

The development of hydrogel based scaffold with the capability of enhanced antibacterial effects and wound healing is the promising strategy for the treatment of wound tissues with bacterial infection. Herein, we fabricated a hollow channeled hydrogel scaffold based on the mixture of dopamine modified alginate (Alg-DA) and gelatin via co-axial 3D printing for the treatment of bacterial-infected wound. The scaffold was crosslinked by copper/calcium ions, which could enhance the structural stability and mechanical properties. Meanwhile, copper ions crosslinking endowed the scaffold with good photothermal effects. The photothermal effect and copper ions showed excellent antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Moreover, the hollow channels and the sustained released copper ions could stimulate angiogenesis and accelerate wound healing process. Thus, the prepared hollow channeled hydrogel scaffold might be a potential candidate for promoting wound healing application.

Construction of a lipid metabolism-related risk model for hepatocellular carcinoma by single cell and machine learning analysis.

One of the most common cancers is hepatocellular carcinoma (HCC). Numerous studies have shown the relationship between abnormal lipid metabolism-related genes (LMRGs) and malignancies. In most studies, the single LMRG was studied and has limited clinical application value. This study aims to develop a novel LMRG prognostic model for HCC patients and to study its utility for predictive, preventive, and personalized medicine. We used the single-cell RNA sequencing (scRNA-seq) dataset and TCGA dataset of HCC samples and discovered differentially expressed LMRGs between primary and metastatic HCC patients. By using the least absolute selection and shrinkage operator (LASSO) regression machine learning algorithm, we constructed a risk prognosis model with six LMRGs (AKR1C1, CYP27A1, CYP2C9, GLB1, HMGCS2, and PLPP1). The risk prognosis model was further validated in an external cohort of ICGC. We also constructed a nomogram that could accurately predict overall survival in HCC patients based on cancer status and LMRGs. Further investigation of the association between the LMRG model and somatic tumor mutational burden (TMB), tumor immune infiltration, and biological function was performed. We found that the most frequent somatic mutations in the LMRG high-risk group were CTNNB1, TTN, TP53, ALB, MUC16, and PCLO. Moreover, naïve CD8+ T cells, common myeloid progenitors, endothelial cells, granulocyte-monocyte progenitors, hematopoietic stem cells, M2 macrophages, and plasmacytoid dendritic cells were significantly correlated with the LMRG high-risk group. Finally, gene set enrichment analysis showed that RNA degradation, spliceosome, and lysosome pathways were associated with the LMRG high-risk group. For the first time, we used scRNA-seq and bulk RNA-seq to construct an LMRG-related risk score model, which may provide insights into more effective treatment strategies for predictive, preventive, and personalized medicine of HCC patients.

Peroxymonosulfate as inducer driving interfacial electron donation of pollutants over oxygen-rich carbon-nitrogen graphene-like nanosheets for water treatment.

Herein, a novel metal-free catalyst consisting of multiporous oxygen-rich carbon-nitrogen graphene-like nanosheets (OLAA-CN NSs) is first developed through a staged temperature-programmed calcination of l-ascorbic acid (LAA)-modified dicyandiamide precursor. It is found that the oxygen species from l-ascorbic acid (OLAA) are introduced into the graphene-like basic matrix and replace partial N atoms to form the COC-R structure, leading to the non-uniform distribution of electrons on the catalyst surface, and the formation of electron-rich centers around the COC microareas according to a series of characterization techniques. As a result, OLAA-CN NSs exhibits excellent performance for refractory pollutant removal in the presence of peroxymonosulfate (PMS) and dissolved oxygen. Some pollutants with complex structures are even completely degraded within only 1 min. The interface reaction mechanism is further revealed that PMS mainly acts as an active inducer to drive the electron donation of pollutants over OLAA-CN NSs. These electrons are finally utilized by dissolved oxygen to generate reactive oxygen species (ROS) through the interface process. This reaction system results in pollutants that can either be cleaved directly by surface oxidation process or degraded by the attack of the generated ROS, such as singlet oxygen (1O2) and superoxide radicals (O2•-), through oxygen activation, which significantly reduces the resource and energy consumption in advanced wastewater treatment by harnessing the energy of pollutants and dissolved oxygen in the water.

Multiscale Hierarchical Architecture-Based Bioactive Scaffolds for Versatile Tissue Engineering.

Artificial construction from tendon to bone remains a formidable challenge in tissue engineering owing to their structural complexity. In this work, bioinspired calcium silicate nanowires and alginate composite hydrogels are utilized as building blocks to construct multiscale hierarchical bioactive scaffolds for versatile tissue engineering from tendon to bone. By integrating 3D printing technology and mechanical stretch post-treatment in a confined condition, the obtained composite hydrogels possess bioinspired reinforcement architectures from nano- to submicron- to microscale with significantly enhanced mechanical properties. The biochemical and topographical cues of the composite hydrogel scaffolds provide much more efficient microenvironment to the rabbit bone mesenchymal stem cells and rabbit tendon stem cells, leading to ordered alignment and improved differentiation. The composite hydrogels markedly promote in vivo tissue regeneration from bone to tendon, especially fibrocartilage transitional tissue. Therefore, such calcium silicate nanowires/alginate composite hydrogels with multiscale hierarchical structures have potential application for tissue regeneration from tendon to bone. This work provides an innovative strategy to construct multiscale hierarchical architecture-based scaffolds for tendon/bone engineering.

Single-Cell Transcriptome Comparison of Bladder Cancer Reveals Its Ecosystem.

Bladder carcinoma (BLCA) is a highly heterogeneous disease, and the underlying biological behavior is still poorly understood. Here, single-cell RNA sequencing was performed on four clinical samples of different grades from three patients, and 26,792 cell transcriptomes were obtained revealing different tumor ecosystems. We found that N-glycan biosynthesis pathway was activated in high-grade tumor, but TNF-related pathway was activated in cystitis glandularis. The tumor microenvironment (TME) of different samples showed great heterogeneity. Notably, cystitis glandularis was dominated by T cells, low-grade and high-grade tumors by macrophages, while TME in patient with high-grade relapse by stromal cells. Our research provides single-cell transcriptome profiles of cystitis glandularis and BLCA in different clinical states, and the biological program revealed by single-cell data can be used as biomarkers related to clinical prognosis in independent cohorts.

3D printed concentrated alginate/GelMA hollow-fibers-packed scaffolds with nano apatite coatings for bone tissue engineering.

Three-dimensional grafts/scaffolds with hierarchically biomimetic features from nano to macro scale and high porosity are required for bone tissue engineering. In this study, biomimetic organic/inorganic composite scaffolds with high porosity (78.7 ± 3.2%) and features from nano (nano apatite coatings) to macro (macro pores and hollow channels) scale were fabricated based on highly concentrated alginate/GelMA bioinks via co-axial 3D printing and in situ mineralization under mild conditions. Nano apatites were coated on both inner and outer surfaces of the hollow fiber scaffolds, homogeneously. Proteins were directly loaded in the bioinks achieving sustained release from the scaffolds over 28 days. The in vitro cell experiments showed that the scaffolds with good biocompatibility could support cells adhesion and proliferation. The nano apatite coatings presented remarkable osteogenic capability. The in vivo study indicated that the hollow fiber scaffolds with biomimetic nano apatite coatings showed the capability to enhance bone formation after 12 weeks of implantation. In conclusion, the prepared biomimetic organic/inorganic scaffolds with homogeneous nano apatite coatings and hollow channels structures might be potential candidates for bone tissue engineering.

Vascularization in tissue engineering: The architecture cues of pores in scaffolds.

Vascularization is a key event and also still a challenge in tissue engineering. Many efforts have been devoted to the development of vascularization based on cells, growth factors, and porous scaffolds in the past decades. Among these efforts, the architecture features of pores in scaffolds played important roles for vascularization, which have attracted increasing attention. It has been known that the open macro pores in scaffolds could facilitate cell migration, nutrient, and oxygen diffusion, which then could promote new tissue formation and vascularization. The pore parameters are the important factors affecting cells response and vessel formation. Thus, this review will give an overview of the current advances in the effects of pore parameters on vascularization in tissue engineering, mainly including pore size, interconnectivity, pore size distribution, pore shape (channel structure), and the micro/nano-surface topography of pores.

ZnL2-BPs Integrated Bone Scaffold under Sequential Photothermal Mediation: A Win-Win Strategy Delivering Antibacterial Therapy and Fostering Osteogenesis Thereafter.

Implant-related infections are serious complications after bone surgery and can compromise the intended functions of artificial implants, leading to surgical failure and even amputation in severe cases. Various strategies have been proposed to endow bone implants with the desirable antibacterial properties, but unfortunately, most of them inevitably suffer from some side effects detrimental to normal tissues. In this study, a multifunctional bone implant is designed to work in conjunction with sequential photothermal mediation, which can deliver antibacterial therapy (<50 °C) in the early stage and foster bone regeneration (40-42 °C) subsequently. Black phosphorus nanosheets (BPs) are coordinated with zinc sulfonate ligand (ZnL2), and the ZnL2-BPs are integrated into the surface of a hydroxylapatite (HA) scaffold to produce ZnL2-BPs@HAP. In this design, BPs produce the photothermal effects and ZnL2 increases the thermal sensitivity of peri-implant bacteria by inducing envelope stress. The biosafety of the antibacterial photothermal treatment is improved due to the mild temperature, and furthermore, gradual release of Zn2+ and PO43- from the scaffold facilitates osteogenesis in the subsequent stage of bone healing. This strategy not only broadens the biomedical applications of photothermal treatment but also provides insights into the design of multifunctional biomaterials in other fields.

3D Printed Wesselsite Nanosheets Functionalized Scaffold Facilitates NIR-II Photothermal Therapy and Vascularized Bone Regeneration.

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor-initiated bone defects. Such scaffolds are usually composed of a near-infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long-term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR-I) with intrinsic poor tissue penetration depth. Also, most of these agents are non-bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR-II photothermal conversion agent (Wesselsite [SrCuSi4 O10 ] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as-designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR-II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor-induced bone defects.

3D printed hydrogel/PCL core/shell fiber scaffolds with NIR-triggered drug release for cancer therapy and wound healing.

Hydrogel based scaffolds with the ability of on-demand drug delivery gained increasing interests for localized cancer therapy and tissue engineering application. However, most drug-loaded hydrogels are generally not suitable for long-term drug delivery, because of the uncontrolled diffusion of drugs from the swollen hydrogels. Therefore, in this study, a core/shell fiber scaffold was fabricated by coating a homogeneous layer of polycaprolactone (PCL) on the 3D printed alginate-gelatin hydrogel scaffolds. The PCL coatings could reduce the free diffusion of drugs from the core gels. Subsequently, polydopamine (PDA) was coated on the Gel/PCL core/shell scaffolds, endowing the scaffolds with great photothermal effects. Thus, near-infrared (NIR) laser triggered on-demand drug release was realized in this system due to the thermally induced sol-gel transition of the core gels. The released drugs (doxorubicin) and photothermal therapy could effectively prohibit or ablate tumor in vitro and in vivo. Additionally, the Gel/PCL/PDA core/shell scaffold could serve as platform for promoting wound healing. Therefore, the reported Gel/PCL/PDA core/shell scaffolds have the potential for application in localized cancer therapy and tissue regeneration. Especially for those cancer patients suffering surgical resection, the scaffolds could be implanted in the resection site to kill the residual or recurrent cancer cells, as well as to repair the tissue defects caused by surgery. STATEMENT OF SIGNIFICANCE: This paper reported a facile strategy to realize stimuli-triggered on demand drug release in vitro and in vivo. Polycaprolactone (PCL) and polydopamine were sequentially deposited on the surface of 3D printed drug-loaded alginate/gelatin scaffold. PCL encapsulation could effectively reduce the free diffusion of drugs from the core hydrogel, achieving sustained drug release. Polydopamine with good photothermal effects endowed the scaffold with stimuli-triggered drug release in response to near-infrared (NIR) laser irradiation. This scaffold could be applied for localized cancer therapy and tissue regeneration. Especially for those cancer patients suffering surgical resection, the scaffolds could be implanted in the resection site to kill the residual or recurrent cancer cells, as well as to repair the tissue defects caused by surgery.

π-π conjugation driving peroxymonosulfate activation for pollutant elimination over metal-free graphitized polyimide surface.

A novel metal-free catalyst consisting of typical flower-like graphitized polyimide (g-PI) is first synthesized via an enhanced hydrothermal polymerization process, and it exhibits excellent performance for pollutant removal through peroxymonosulfate (PMS) activation over a wide pH range (3-11). The catalyst is especially effective for attacking the endocrine disruptor bisphenol A (BPA), which can be completely degraded in a short time. Based on the results of characterization, g-PI is consisted of abundant aromatic frameworks with π conjugates based on C-O-C linkages and N-hybrid rings, which play essential roles in the subsequent degradation of pollutants. In the g-PI/PMS/BPA system, BPA (rich in π bonds) is preferentially adsorbed to the catalyst surface through π-π interactions, accompanied by a decrease in its activation energy to produce surface-adsorbed BPA*. This species can be directly attacked and degraded by PMS without the need for the radical processes, which saves the energy required for the intermediate activation process of PMS. On the other hand, the electrons obtained from pollutants are rapidly transferred to the O center, driving PMS activation to generate free radicals. The synergetic interface process offers excellent potential for practical wastewater purification.

Magnetically-driven drug and cell on demand release system using 3D printed alginate based hollow fiber scaffolds.

Local delivery of drugs, proteins and living cells with on demand release manner using porous scaffolds has been widely used in the field of tissue engineering and cancer therapies. Drugs directly loaded in the porous scaffolds, are generally prone to free diffuse especially for long term incubation. Herein, in this study, hollow fiber alginate/iron oxide nanoparticles scaffolds were prepared by coaxial 3D printing with drugs, protein or living cells encapsulating in the core part (low concentration of alginate gels). Magnetically-driven on demand release was realized by extruding the loaded drugs, proteins and cells from the core part of the hollow fibers due to the deformation of the scaffolds under magnetic field. Additionally, the hollow fibers could sever as diffusion barriers to reduce uncontrolled diffusion of drugs, proteins and cells from scaffolds in the conditions of no required stimulation. The factors influencing the deformation of the scaffolds, as well as the release behavior were investigated. The data indicated that the scaffolds prepared by 10 wt% of alginate with 13% of iron oxide nanoparticles after crosslinking using 0.1 M CaCl2 solution for 10 s showed repeated on demand release capability in vitro and in vivo under intermittently magnetic stimulation. Thus, this 3D printed alginate/iron oxide nanoparticles hollow scaffolds with on demand controlled delivery capability may prove useful for tissue engineering and disease therapies.

Photoactivated H2 Nanogenerator for Enhanced Chemotherapy of Bladder Cancer.

Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H2 nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H2 production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H2 gas in situ upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H2 gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.

3D printed core-shell hydrogel fiber scaffolds with NIR-triggered drug release for localized therapy of breast cancer.

Localized therapy using hydrogels-based drug delivery system (DDS) is a promising strategy for the treatment of diseases such as cancer in superficial tissues. In this study, we presented a facile method to prepare core-shell hydrogel fibers/scaffolds with controlled drug delivery and designed structures for the treatment of the residual breast cancer and prevention of local recurrence after surgery. Mixtures of polydopamine (PDA) and concentrated alginate inks (15.3 wt%) as the shell layer, and drug-loaded temperature-sensitive hydrogels as the core part were co-injected and coaxial 3D printed into core-shell hydrogel fibers and scaffolds. Under near infrared (NIR) irradiation, PDA with excellent photothermal effect could raise the temperature of core-shell fibers, which induced the gel-sol transition of the core gels, and subsequently resulted in the drug release from the loosened hydrogel network. The photothermal effect and the released drugs could eliminate cancer effectively. Thus, our prepared core/shell fibers and scaffolds with NIR-triggered on-demand drug release would be promising candidates to fill the cavity of breast tissues after surgical resection of cancer achieving a therapeutic effect for the residual and recurred cancer.

The clinicopathological and prognostic significance of P27kip in hepatocellular carcinoma patients: A systemic review and meta-analysis.

OBJECTIVES: P27kip is a cyclin-dependent kinase inhibitor that has gained importance as a biomarker in human malignant tumors. However, the potential role of P27kip in hepatocellular carcinoma remains unclear. The aim of this meta-analysis was to explore whether P27kip acts as prognostic and clinicopathological roles in hepatocellular carcinoma patients. METHODS/MATERIALS: An electronic search based on three databases, PubMed, Embase, and Web of Science, was performed to select a sufficient number of studies. Pooled hazard ratio (HR) and odds ratio (OR) were used as estimates to investigate the association among P27kip expression, prognosis and clinicopathological features. RESULTS: In total, we identified 18 studies with 1774 hepatocellular carcinoma patients. The result derived from four studies revealed a significant positive association between lower P27kip levels and shorter overall survival (HR = 0.550, 95% CI: 0.464-0.652, P < 0001) and disease-free survival (HR = 0.420, 95% CI: 0.308-0.571, P < 0.0001). Analyses of the clinicopathological features and P27kip expression also showed that a positive rate of P27kip was significantly lower in a larger sized tumor (OR = 0.538, 95% CI: 0.315-0.919, P = 0.023). The results also revealed that lower P27kip levels were correlated with poorer differentiation (0.416, 95% CI: 0.178-0.971, P = 0.043). Additionally, the pooled OR of 0.389 also presented a significant correlation between P27kip underexpression and the metastasis of HCCs (95% CI: 0.155-0.975, P = 0.044). CONCLUSIONS: This analysis suggests a strong association among P27kip underexpression, poorer prognosis and aggressive progression of hepatocellular carcinoma in patients. P27kip may be a tumor suppressor for predicting the progression and survival outcome in patients with hepatocellular carcinomas.