Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.

Background: Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT). Methods: Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model. Results: The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05). Conclusion: For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.

Polymeric nanoparticles (PNPs) for oral delivery of insulin.

Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. Oral insulin administration, on the other hand, is seriously hampered by gastrointestinal enzymes, wide pH range, mucus and mucosal layers, which limit insulin oral bioavailability to ≤ 2%. Therefore, a large number of technological solutions have been proposed to increase the oral bioavailability of insulin, in which polymeric nanoparticles (PNPs) are highly promising for oral insulin delivery. The recently published research articles chosen for this review are based on applications of PNPs with strong future potential in oral insulin delivery, and do not cover all related work. In this review, we will summarize the controlled release mechanisms of oral insulin delivery, latest oral insulin delivery applications of PNPs nanocarrier, challenges and prospect. This review will serve as a guide to the future investigators who wish to engineer and study PNPs as oral insulin delivery systems.

Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function.

Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4+, CD8+ T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-ß3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.

Chiral Hybrid Germanium(II) Halide with Strong Nonlinear Chiroptical Properties.

Due to the pronounced anisotropic response to circularly polarized light, chiral hybrid organic-inorganic metal halides have been regarded as promising candidates for the application in nonlinear chiroptics, especially for the second-harmonic generation circular dichroism (SHG-CD) effect. However, designing novel lead-free chiral hybrid metal halides with large anisotropy factors and high laser-induced damage thresholds (LDT) of SHG-CD remains challenging. Herein, we develop the first chiral hybrid germanium halide, (R/S-NEA)3 Ge2 I7 ⋅H2 O (R/S-NGI), and systematically investigated its linear and nonlinear chiroptical properties. S-NGI and R-NGI exhibit large anisotropy factors (gSHG-CD ) of 0.45 and 0.48, respectively, along with a high LDT of 38.46 GW/cm2 ; these anisotropy factors were the highest values among the reported lead-free chiral hybrid metal halides. Moreover, the effective second-order nonlinear optical coefficient of S-NGI could reach up to 0.86 pm/V, which was 2.9 times higher than that of commercial Y-cut quartz. Our findings facilitate a new avenue toward lead-free chiral hybrid metal halides, and their implementation in nonlinear chiroptical applications.

Development of a difficulty scoring system for laparoscopic pancreatoduodenectomy in the initial stage of the learning curve: a retrospective cohort study.

BACKGROUND: It remains uncertain how surgeons can safely pass the learning curve of laparoscopic pancreatoduodenectomy (LPD) without potentially harming patients. We aimed to develop a difficulty scoring system (DSS) to select an appropriate patient for surgeons. MATERIALS AND METHODS: A total of 773 elective pancreatoduodenectomy surgeries between July 2014 and December 2019, including 346 LPD and 427 open pancreatoduodenectomy cases, were included. A 10-level DSS for LPD was developed, and an additional 77 consecutive LPD surgeries which could provide information of the learning stage I of LPD externally validated its performance between December 2019 and December 2021. RESULTS: The incidences of postoperative complications (Clavien-Dindo≥III) gradually decreased from the learning curve stage I-III (20.00, 10.94, 5.79%, P =0.008, respectively). The DSS consisted of the following independent risk factors: (1) tumor location, (2) vascular resection and reconstruction, (3) learning curve stage, (4) prognostic nutritional index, (5) tumor size, and (6) benign or malignant tumor. The weighted Cohen's κ statistic of concordance between the reviewer's and calculated difficulty score index was 0.873. The C -statistics of DSS for postoperative complication (Clavien-Dindo≥III) were 0.818 in the learning curve stage I. The patients with DSS<5 had lower postoperative complications (Clavien-Dindo≥III) than those with DSS≥5 (4.35-41.18%, P =0.004) in the training cohort and had a lower postoperative pancreatic fistula (19.23-57.14%, P =0.0352), delayed gastric emptying (19.23-71.43%, P =0.001), and bile leakage rate (0.00-21.43%, P =0.0368) in validation cohort in the learning curve stage I. CONCLUSION: We developed and validated a difficulty score model for patient selection, which could facilitate the stepwise adoption of LPD for surgeons at different stages of the learning curve.

Highly Efficient and Stable FA-Based Quasi-2D Ruddlesden-Popper Perovskite Solar Cells by the Incorporation of ß-Fluorophenylethanamine Cations.

2D Ruddlesden-Popper (2D RP) perovskite, with attractive environmental and structural stability, has shown great application in perovskite solar cells (PSCs). However, the relatively inferior photovoltaic efficiencies of 2D PSCs limit their further application. To address this issue, ß-​fluorophenylethanamine (ß-​FPEA) as a novel spacer cation is designed and employed to develop stable and efficient quasi-2D RP PSCs. The strong dipole moment of the ß-​FPEA enhances the interactions between the cations and [PbI6 ]4- octahedra, thus improving the charge dissociation of quasi-2D RP perovskite. Additionally, the introduction of the ß-​FPEA cation optimizes the energy level alignment, improves the crystallinity, stabilizes both the mixed phase and a-FAPbI3 phase of the quasi-2D RP perovskite film, prolongs the carrier diffusion length, increases the carrier lifetime and decreases the trap density. By incorporating the ß-​FPEA, the quasi-2D RP PSCs exhibit a power conversion efficiency (PCE) of 16.77% (vs phenylethylammonium (PEA)-based quasi-2D RP PSCs of 12.81%) on PEDOT:PSS substrate and achieve a champion PCE of 19.11% on the PTAA substrate. It is worth noting that the unencapsulated ß-​FPEA-based quasi-2D RP PSCs exhibit considerably improved thermal and moisture stability. These findings provide an effective strategy for developing novel spacer cations for high-performance 2D RP PSCs.

Calycosin-7-glucoside promotes mitochondria-mediated apoptosis in hepatocellular carcinoma by targeting thioredoxin 1 to regulate oxidative stress.

Thioredoxin1 (TRX1) is a key protein that regulates redox and is considered to be a key target for cancer therapy. Flavonoids have been proven to have good antioxidant and anticancer activities. This study aimed to investigate whether the flavonoid calycosin-7-glucoside (CG) exerts an anti-hepatocellular carcinoma (HCC) role by targeting TRX1. Different doses of CG were used to treat HCC cell lines Huh-7 and HepG2 to calculate the IC50. On this basis, the effects of low, medium and high doses of CG on cell viability, apoptosis, oxidative stress and TRX1 expression of HCC cells were investigated in vitro. Also, HepG2 xenograft mice were used to evaluate the role of CG on HCC growth in vivo. The binding mode of CG and TRX1 was explored by molecular docking. Then si-TRX1 was used to further discover the effects of TRX1 on CG inhibition of HCC. Results found that CG dose-dependent decreased the proliferation activity of Huh-7 and HepG2 cells, induced apoptosis, significantly activated oxidative stress and inhibited TRX1 expression. In vivo experiments also showed that CG dose-dependent regulated oxidative stress and TRX1 expression, and promoted the expression of apoptotic proteins to inhibit HCC growth. Molecular docking confirmed that CG had a good binding effect with TRX1. Intervention with TRX1 significantly inhibited the proliferation of HCC cells, promoted apoptosis, and further promoted the effect of CG on the activity of HCC cells. In addition, CG significantly increased ROS production, reduced mitochondrial membrane potential, regulated the expression of Bax, Bcl-2 and cleaved-caspase-3, and activated mitochondria-mediated apoptosis. And si-TRX1 enhanced the effects of CG on mitochondrial function and apoptosis of HCC, suggesting that TRX1 participated in the inhibitory effect of CG on mitochondria-mediated apoptosis of HCC. In conclusion, CG exerts anti-HCC activity by targeting TRX1 to regulate oxidative stress and promote mitochondria-mediated apoptosis.

Cytotoxic phenyl polyketides from Hypericum curvisepalum N. Robson.

(±)-Hypecurvone A (1) and B (2), two new undescribed phenyl polyketides, along with seven known analogues (3-9) were isolated from the whole plant of Hypericum curvisepalum. Chiral separation of 1 and 2 yielded two pairs of enantiomers 1a/1b and 2a/2b, respectively. The structures of these compounds were elucidated by extensive spectroscopic analyses and ECD spectra simulations. All isolates exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells, and compound 3 also showed weak cytotoxicity toward MGC-803 cells. The cytotoxicity of these compounds was found to be related to enhanced mitochondria-mediated apoptosis and inhibition of the G2/M phase of the cell cycle.

Hypoxia activated HGF expression in pancreatic stellate cells confers resistance of pancreatic cancer cells to EGFR inhibition.

BACKGROUND: Epidermal growth factor receptor (EGFR) is an essential target for cancer treatment. However, EGFR inhibitor erlotinib showed limited clinical benefit in pancreatic cancer therapy. Here, we showed the underlying mechanism of tumor microenvironment suppressing the sensitivity of EGFR inhibitor through the pancreatic stellate cell (PSC). METHODS: The expression of alpha-smooth muscle actin (α-SMA) and hypoxia marker in human pancreatic cancer tissues were detected by immunohistochemistry, and their correlation with overall survival was evaluated. Human immortalized PSC was constructed and used to investigate the potential effect on pancreatic cancer cell lines in hypoxia and normoxia. Luciferase reporter assay and Chromatin immunoprecipitation were performed to explore the potential mechanisms in vitro. The combined inhibition of EGFR and Met was evaluated in an orthotopic xenograft mouse model of pancreatic cancer. FINDINGS: We found that high expression levels of α-SMA and hypoxia markers are associated with poor prognosis of pancreatic cancer patients. Mechanistically, we demonstrated that hypoxia induced the expression and secretion of HGF in PSC via transcription factor HIF-1α. PSC-derived HGF activates Met, the HGF receptor, suppressing the sensitivity of pancreatic cancer cells to EGFR inhibitor in a KRAS-independent manner by activating the PI3K-AKT pathway. Furthermore, we found that the combination of EGFR inhibitor and Met inhibitor significantly suppressed tumor growth in an orthotopic xenograft mouse model. INTERPRETATION: Our study revealed a previously uncharacterized HIF1α-HGF-Met-PI3K-AKT signaling axis between PSC and cancer cells and indicated that EGFR inhibition plus Met inhibition might be a promising strategy for pancreatic cancer treatment. FUNDING: This study was supported by The National Natural Science Foundation of China.

Three New Xanthones from Hypericum scabrum and Their Quorum Sensing Inhibitory Activities against Chromobacterium violaceum.

Quorum sensing (QS) plays an important role in the production of virulence factors and pathogenicity in pathogenic bacteria and is, therefore, a hopeful target to fight against bacterial infections. During our search for natural QS inhibitors, two new xanthonolignoids (1 and 2), each existing as a racemic mixture, one new simple oxygenated xanthone (7), and eight known analogs (3-6, 8-11) were isolated from Hypericum scabrum Linn. Chiral separation of 1 yielded a pair of enantiomers 1a and 1b. The structures of these compounds were elucidated by spectroscopic analysis and ECD (electrostatic circular dichroism) calculations. All isolates were evaluated for their QS inhibitory activity against Chromobacterium violaceum. Both 9 and 10 exhibited the most potent QS inhibitory effects with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 31.25 and 62.5 µM, respectively. Crystal violet staining was used to further evaluate the biofilm inhibition potential of compounds 7, 9 and 10, and the formation of biofilms increased with decreasing drug concentration in a classic dose-dependent manner. The results of a cytotoxicity assay revealed that compounds 7, 9 and 10 exhibited no cytotoxic activity on PC-12 cells at the tested concentration.

Natural Polysaccharide-Based Nanodrug Delivery Systems for Treatment of Diabetes.

In recent years, natural polysaccharides have been considered as the ideal candidates for novel drug delivery systems because of their good biocompatibility, biodegradation, low immunogenicity, renewable source and easy modification. These natural polymers are widely used in the designing of nanocarriers, which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. A great deal of studies could be focused on developing polysaccharide nanoparticles and promoting their application in various fields, especially in biomedicine. In this review, a variety of polysaccharide-based nanocarriers were introduced, including nanoliposomes, nanoparticles, nanomicelles, nanoemulsions and nanohydrogels, focusing on the latest research progress of these nanocarriers in the treatment of diabetes and the possible strategies for further study of polysaccharide nanocarriers.

Combined effects of multi-land use decisions and climate change on water-related ecosystem services in Northeast China.

Land use intensification and climate change have resulted in substantial changes in the provision of ecosystem services, particularly in China that experienced sharp increases in population growth and demands for goods and energy. To protect the environment and restore the degraded ecosystems, the Chinese government has implemented multiple national ecological restoration projects. Yet, the combined effects of climate change and land use and land cover change (LULCC) over large spatial scales that brace multiple land use decisions and great environmental heterogeneity remain unclear. We assessed the combined effects of LULCC and climate change on water-related ecosystem services (water provision and soil conservation services) from 1990s to 2020s in Northeast China using the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model. We found that water yield decreased by 9.78% and soil retention increased by 30.51% over the past 30 years. LULCC and climate change exerted negative effects on water yield whereas they both enhanced soil retention; LULCC interacted with climate change to have relatively small inhibitory effects on water yield and large facilitation effects on soil retention. Changes in water yield were mainly attributed to climate change, while soil retention was largely influenced by LULCC and its interaction with climate change. Our research highlights the importance of land use decisions and its interactive effects with climate change on ecosystem services in a heavily disturbed temperate region, and provides important information to inform future land management and policy making for sustaining diverse ecosystem services and ensuring human wellbeing.

WO3·nH2O Crystals with Controllable Morphology/Phase and Their Optical Absorption Properties.

In this work, a one-step hydrothermal route is developed to prepare WO3·nH2O crystals with various morphology/phases, for which any surfactants, templates, or structure-directing agents are not used. Five types of WO3·nH2O crystals, including o-WO3·H2O nanoplates, rectangular m-WO3 nanosheets, o-WO3·0.33H2O microspheres, h-WO3 nanorods, and bundle-like h-WO3 hierarchical structures, are successfully obtained by adjusting the amount of H2SO4 and reaction temperature. According to the experimental results, the formation mechanism for various WO3·nH2O species is proposed. In addition, the optical absorption properties of these WO3·nH2O crystals are also investigated by UV-vis absorption spectra.

Perovskite metasurfaces with large superstructural chirality.

Recent attempts to synthesize hybrid perovskites with large chirality have been hampered by large size mismatch and weak interaction between their structure and the wavelength of light. Here we adopt a planar nanostructure design to overcome these limitations and realize all-dielectric perovskite metasurfaces with giant superstructural chirality. We identify a direct spectral correspondence between the near- and the far- field chirality, and tune the electric and magnetic multipole moments of the resonant chiral metamolecules to obtain large anisotropy factor of 0.49 and circular dichroism of 6350 mdeg. Simulations show that larger area metasurfaces could yield even higher optical activity, approaching the theoretical limits. Our results clearly demonstrate the advantages of nanostructrure engineering for the implementation of perovskite chiral photonic, optoelectronic, and spintronic devices.

Robust Optimal Control for the Vehicle Suspension System With Uncertainties.

The suspension system is an important unit that affects vehicle performance, including handling stability and riding comfort. In order to improve vehicle performances, a novel robust optimal control strategy for the active suspension system in vehicles is proposed. To handle the parameter uncertainties and external random disturbances, the proposed optimal control strategy is designed by using the combination of the linear quadratic regulator (LQR) optimal control and sliding-mode control. First, by using the nominal model of the active suspension system without the uncertain parameters and the external random disturbances, an optimal control performance index is given, and the initial optimal controller is designed by using the LQR control strategy. Then, to handle the parameter uncertainties and the external disturbances, a robust optimal integral sliding-mode control strategy based on the initial optimal controller is designed, which not only can achieve the optimal control objective but also has good robustness to the uncertain parameters and external disturbances. By using the Lyapunov stability theory, stability analysis of the proposed robust optimal integral sliding-mode control strategy is performed. Finally, the collaborative simulation platform based on the Carsim and MATLAB/Simulink is developed. The simulation results illustrate the advantage of the proposed robust optimal control strategy for the suspension system.

Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors.

BACKGROUND: The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS: We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS: Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION: These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.

Development and Validation of a Nomogram to Predict Survival in Pancreatic Head Ductal Adenocarcinoma After Pancreaticoduodenectomy.

BACKGROUND: Pancreatic head ductal adenocarcinoma (PHDAC) patients with the same tumor-node-metastasis (TNM) stage may share different outcomes after pancreaticoduodenectomy (PD). Therefore, a novel method to identify patients with poor prognosis after PD is urgently needed. We aimed to develop a nomogram to estimate survival in PHDAC after PD. METHODS: To estimate survival after PD, a nomogram was developed using the Tongji Pancreatic cancer cohort comprising 355 PHDAC patients who underwent PD. The nomogram was validated under the same conditions in another cohort (N = 161) from the National Taiwan University Hospital. Prognostic factors were assessed using LASSO and multivariate Cox regression models. The nomogram was internally validated using bootstrap resampling and then externally validated. Performance was assessed using concordance index (c-index) and calibration curve. Clinical utility was evaluated using decision curve analysis (DCA), X-tile program, and Kaplan-Meier curve in both training and validation cohorts. RESULTS: Overall, the median follow-up duration was 32.17 months, with 199 deaths (64.82%) in the training cohort. Variables included in the nomogram were age, preoperative CA 19-9 levels, adjuvant chemotherapy, Tongji classification, T stage, N stage, and differentiation degree. Harrell's c-indices in the internal and external validation cohorts were 0.79 (95% confidence interval [CI], 0.76-0.82) and 0.83 (95% CI, 0.78-0.87), respectively, which were higher than those in other staging systems. DCA showed better clinical utility. CONCLUSION: The nomogram was better than TNM stage and Tongji classification in predicting PHDAC patients' prognosis and may improve prognosis-based selection of patients who would benefit from PD.

Helical mesoscopic crystals based on an achiral charge-transfer complex with controllable untwisting/breaking.

The development of synthetic helical structures from achiral molecules and stimulus-responsive shape transformations are vital for biomimetics and mechanical actuators. A stimulus regarded as the force to induce chirality modulation plays a significant role in the helical supramolecular structure design through symmetry breaking. Herein, we synthesized a metastable complex Form 1 crystal composed of pyrene and (4,8-bis(dicyanomethylene)-4,8-dihydrobenzo[1,2-b:4,5-b']-dithiophen-e) DTTCNQ components with a torsional backbone by C-H⋯N hydrogen bonds via a quick cooling method. The helix motion kinetics of Form 1 depends on the intrinsic factor (crystal thickness) and external stimuli (polar solvents). The self-assembled helical microstructures grow into needle-like crystals in liquid media via an untwistingprocess. Furthermore, they undergo predictable deformation of untwisting or breaking under a stimulus-responsive strain-relaxing phase transformation. This work illustrates a new approach in the mediated formation of helical morphologies from achiral binary supramolecules and dynamic motion, which is vital for biomimetics and mechanical actuators.

Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment.

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy.

New staging classification for pancreatic neuroendocrine neoplasms combining TNM stage and WHO grade classification [].

AJCC TNM stage and WHO grade (G) are two widely used staging systems to guide clinical management for pancreatic neuroendocrine neoplasms (panNENs), based on clinical staging and pathological grading information, respectively. We proposed to integrate TNM stage and G grade into one staging system (TNMG) and to evaluate its clinical application as a prognostic indicator for panNENs. Accordingly, 5254 patients diagnosed with panNENs were used to evaluate and to validate the applicability of TNMG to panNENs. The predictive accuracy of TNMG system was compared with that of each separate staging/grading system. We found that TNM stage and G grade were independent risk factors for survival in both the Surveillance, Epidemiology, and End Result (SEER) and multicenter series. The interaction effect between TNM stage and G grade was significant. Twelve subgroups combining the TNM stage and G grade were proposed in the TNMG stage, which were classified into five stages TNMG. According to the TNMG staging classification in the SEER series, the estimated median survival for stages I, II, III, IV, and V were 203, 174, 112, 61, and 8 months, respectively. The predictive accuracy of TNMG stage was higher than that of TNM stage and G grade used independently. The TNMG stage classification was more accurate in predicting panNEN patient's prognosis than either the TNM stage or G grade.