Search

Abstract Polymer composite scaffolds hold promise in bone tissue engineering due to their biocompatibility, mechanical properties, and reproducibility. Among these materials, polylactic acid (PLA), a biodegradable plastics has gained attention for its processability characteristics. However, a deeper understanding of how PLA scaffold surface properties influence cell behavior is enssential for advancing its applications. In this study, 3D-printed PLA scaffolds containing hydroxyapatite (HA) were analyzed using atomic force microscopy and nanomechanical mapping. The addition of HA significantly increased key surface properties compared to unmodified PLA scaffols. Notably, the HA-modified scaffold demonstrated Gaussian distribution of stiffness and adhesive forces, in contrast to the bimodal properties observed in the unmodified PLA scaffolds. Human adipose-derived mesenchymal stem cell (hADMSC) seeded on the 3D-printed PLA scaffolds blended with 10% HA (P10) exhibited strong attachment. After four weeks, osteogenic differentiation of hADMSCs was detected, with calcium deposition reaching 6.76% ± 0.12. These results suggest that specific ranges of stiffness and adhesive forces of the composite scaffold can support cell attachement, and mineralization. The study highlights that tailoring suface properties of composite scaffolds is crucial for modulating cellular interactions, thus advancing the development of effective bone replacement materials.

Abstract Modern human societies are highly dependent on plastic materials, however, the bulk of them are non‐renewable commodity plastics that cause pollution problems and consume large amounts of energy for their thermal processing activities. In this article, a sustainable cellulose hydroplastic material and its composites, that can be shaped repeatedly into various 2D/3D geometries using just water are introduced. In the wet state, their high flexibility and ductility make it conducive for the shaping to take place. In the ambient environment, the wet hydroplastic transits spontaneously into rigid materials with its intended shape in a short time of

Abstract Biological strong and tough materials have been providing original structural designs for developing bioinspired high‐performance composites. However, new synergistic strengthening and toughening mechanisms from bioinspired structures remain yet to be explored and employed to upgrade current carbon material reinforced polymer composites, which are keystone to various modern industries. In this work, from bamboo, the featured cell face‐bridging fibers, are abstracted and embedded in a cellular network structure, and develop an epoxy resin/carbon composite featuring biomimetic architecture through a fabrication approach integrating freeze casting, carbonization, and resin infusion with carbon fibers (CFs) and carbon nanotubes (CNTs). Results show that this bamboo‐inspired crack‐face bridging fiber reinforced composite simultaneously possesses a high strength (430.8 MPa) and an impressive toughness (8.3 MPa m1/2), which surpass those of most resin‐based nanocomposites reported in the literature. Experiments and multiscale simulation models reveal novel synergistic strengthening and toughening mechanisms arising from the 2D faces that bridge the CFs: sustaining and transferring loads to enhance the overall load‐bearing ability and furthermore, incorporating CNTs pullout that resembles the intrinsic toughening at the molecular to nanoscale and strain delocalization, crack branching, and crack deflection as the extrinsic toughening at the microscale. These constitute a new effective and efficient strategy to develop simultaneously strong and tough composites through abstracting and implenting novel bioinspired structures, which contributes to addressing the long‐standingly challenging attainment of both high strength and toughness for advanced structural materials.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) presents the similar trend and prevalence of lymph node metastasis to other biliary tract cancer. There is still a necessity and possibility for the current classification of lymph node in the 8th TNM of iCCA, which is the same as the criteria of hepatoma carcinoma (HCC), to further improve the prognostic capacity. We aim to explore the optimal positive lymph nodes cutoff value that could predict the survival outcomes of patients with iCCA and further establish a prognostic nomogram. Method Clinical characteristics were retrospectively collected in 292 patients with iCCA from Sun Yat-sen University Cancer Center (SYSUCC) for preliminary analysis. A retrospective analysis of 107 patients with iCCA in the First Hospital of Dalian Medical University (FHDMU) was performed for verification. R software was used to determine the optimal cutoff value of positive lymph nodes (PLN) and further establish the nomogram with the Cox regression model in the primary cohort. Results In those patients who were graded into the N1 stage in 8th TNM staging system, the patients with PLN between 1 and 3 showed significantly better overall survival than those patients with more than 4 PLN (P

Abstract Polydimethylsiloxane (PDMS) has been widely used in flexible electronics, soft robotics, and bioelectronics. However, the fabrication of PDMS‐based devices has mostly relied on conventional approaches, such as casting and molding, thereby limiting their potential. Here we fabricate PDMS‐based composites with programmable microstructures by direct ink writing and realize their practical functionalities of four‐dimensional (4D) printing. The mechanical, thermomechanical and magnetic properties of the three‐dimensional‐printed composites can be well tailored by using carbon, metal, or ceramic functional fillers. By taking advantage of the printable, flexible, and magnetic PDMS composites, we demonstrate new practical functionalities of 4D printing by designing programmable architectures, including magnetic‐field‐driven battery cases and patchworks, as well as arbitrary morphing ceramic structures. In particular, 4D‐printed batteries are constructed by PDMS‐based battery cases for the first time, which can be actuated via external magnetic field. This study broadens the paradigm of 4D printing for prospective applications, such as implant batteries, biomimetic engineering, and customized biomedical devices.

Abstract. Objective:. Irreversible electroporation (IRE) is emerging as a new therapy for locally advanced pancreatic cancer (LAPC). We aimed to conduct survival and safety analyses in LAPC patients after treatment with IRE combined with chemotherapy. Methods:. A total of 64 patients with LAPC who had received IRE and chemotherapy were retrospectively collected from August 2015 to March 2019 at Sun Yat-sen University Cancer Center. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier method and compared by the log-rank test. A multivariate Cox regression model was used to determine the prognostic factors of survival. The perioperative complications of IRE were also evaluated. The study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center (approval No. C2021-003). Results:. The median survival of all included patients were 24.63 (95% confidence interval: 21.78–27.49) for overall survival and 13.00 (95% confidence interval: 8.81–17.19) months for progression-free survival, with 96.8%, 51.9%, 18.3%; and 52.3%, 21.5%, 7.9% as the 1-, 2- and 3-year OS and PFS rates, respectively. Tumor size [OS, hazard ratio (HR)=1.768, P = 0.048; PFS, HR = 0.304, P = 0.010], neoadjuvant chemotherapy (OS, HR = 0.338, P = 0.030; PFS, HR = 0.358, P = 0.034), carbohydrate antigen 19-9 variation after IRE (OS, HR = 19.320, P = 0.003; PFS, HR = 14.591, P = 0.021) and tumor response after neoadjuvant chemotherapy (OS, HR = 8.779, P = 0.033; PFS, HR = 5.562, P = 0.008) were predictive factors of survival in patients with LAPC after IRE. Complications were observed in 20.3% of patients. Grade B pancreatic fistula was the most common complication. The complication rates of the late treatment group (6.1%) were significantly lower than those of the first 15 patients after IRE treatment (66.7%). The median length of hospital stay of late treatment group was 8.6 days, which was also shorter than that of the early treatment group (10.0 days). Conclusions:. IRE combined with chemotherapy could improve survival of LAPC patients with acceptable complication rates. Therefore, it may be a suitable method for LAPC but should be validated in prospective randomized trials.

Background: Desmoplasia or rich fibrotic stroma is a typical property of pancreatic cancer (PC), with a significant impact on tumor progression, metastasis, and chemotherapy response. Unusual inflammatory responses are considered to induce fibrosis of tissue, but the expression and clinical significance of inflammatory response-related genes in PC have not been clearly elucidated.Methods: Prognosis-related differentially expressed genes (DEGs) between tumor and normal tissues were identified by comparing the transcriptome data of PC samples based on The Cancer Genome Atlas (TCGA) portal and the Genotype Tissue Expression (GTEx) databases. Samples from the ArrayExpress database were used as an external validation cohort.Results: A total of 27 inflammatory response-related DEGs in PC were identified. Least absolute shrinkage and selection operator (LASSO) analysis revealed three core genes that served as an inflammatory response gene signature (IRGS), and a risk score was calculated. The diagnostic accuracy of the IRGS was validated in the training (n = 176) and validation (n = 288) cohorts, which reliably predicted the overall survival (OS) and disease-free survival (DFS) of patients with PC. Furthermore, multivariate analysis identified the risk score as an independent risk factor for OS and DFS. The comprehensive results suggested that a high IRGS score was correlated with decreased CD8+ T-cell infiltration, increased M2 macrophage infiltration, increased occurrence of stroma-activated molecular subtype and hypoxia, enriched myofibroblast-related signaling pathways, and greater benefit from gemcitabine.Conclusion: The IRGS was able to promisingly distinguish the prognosis, the tumor microenvironment characteristics, and the benefit from chemotherapy for PC.

Thermoelectric technology, which is characterized by the interconversion between heat and electricity, is demonstrated as an efficient and environmentally friendly route for thermal energy harvesting and solid-state cooling devices. The pursuit for high-performance room temperature thermoelectric materials is of significant interest. Here, we proposed a design strategy to dramatically improve the thermoelectric response by constructing a hierarchical multiscale conductor network (AgNWs/CNT) in polymer matrix (PEDOT:PSS). At the optimized composition, the highest Seebeck coefficient and electrical conductivity of base treated ternary PEDOT:PSS/AgNWs/CNT composite are optimized to be 58.6 μV K−1 and ∼1950 S cm−1. Correspondingly, the power factor is thus calculated to be on the order of 670 μW m−1 K−2, which is among one of the highest values compared with previous reports. The underlying mechanism is illustrated based on detailed structure, morphology and electron transport quantification. This work affords a novel strategy for the future development of high-performance room temperature nanocomposite thermoelectrics.

BackgroundThe post-progression survival (PPS) of recurred intrahepatic cholangiocarcinoma (iCCA) patients relates to the characteristics of tumor progression. Moreover, the prediction model of PPS in those patients has not been well established. This study aimed at developing a novel nomogram for predicting PPS in recurred iCCA patients.MethodClinical characteristics were retrospectively collected in 396 patients diagnosed with iCCA from cohorts of Sun Yat-sen University Cancer Center (SYSUCC) and the First Hospital of Dalian Medical University (FHDMU). The PPS in patients with different progression patterns was investigated. The nomogram of PPS was established with the Cox regression model in the primary cohort. Then the nomogram was verified in the external validation cohort.ResultsLiver progression was the commonest pattern (42.08%) in recurred iCCA patients, while patients with local LN progression had significantly better PPS than those with other patterns. The independent prognostic factors comprised elevated CEA levels, tumor differentiation, N stage 8th, adjuvant therapy, Local LN metastasis, Liver Metastasis only, and Multiple Metastasis. The nomogram constructed on these factors achieved satisfied C-indexes of 0.794 (95% CI 0.769–0.828) and 0.827 (0.779–0.876) for the training and validation cohorts, respectively. These values were significantly higher than those of the 8th TNM stage system (all p < 0.001). The recurred iCCA patients could be precisely classified into high- and low-risk groups according to the cutoff point of this nomogram (p < 0.01).ConclusionThe investigation of progression patterns and the development of this nomogram can offer new evidence to precisely postoperative and post-progression management of iCCA patients.

Abstract Background Growing evidence indicates that the systemic inflammatory response plays an important role in cancer development and progression. Several inflammatory markers have been reported to be associated with clinical outcomes in patients with various types of cancer. This study was designed to evaluate the prognostic value of inflammatory indexes in patients with ampullary cancer (AC) who underwent pancreaticoduodenectomy (PD). Methods We retrospectively reviewed the data of 358 patients with AC who underwent PD between 2009 and 2018. R software was used to compare the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) of the inflammation-based indexes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI) and prognostic index (PI), in terms of their predictive value for survival. The survival differences of these indexes were compared by the Kaplan-Meier method and univariate and multivariate analyses were performed to determine the prognostic factors of disease-free survival (DFS) and overall survival (OS). Results The estimated 1-, 2-, and 3-year OS and DFS rates were 83.9, 65.8, and 55.2% and 58.0, 42.8, and 37.8%, respectively, for the entire cohort. The survival differences were significant in terms of OS and DFS when patients were stratified by these inflammation-based indexes. The comparisons of the AUROCs of these inflammation-based indexes illustrated that NLR and PI displayed the highest prognostic value, compared to the other indexes. When NLR and PI were combined, NLR-PI showed even higher AUROC values and was identified as a significant prognostic factor for OS and DFS. Conclusion Specific inflammatory indexes, such as NLR, PLR and dNLR, were found to be able to predict the OS or DFS of patients. As a novel inflammatory index, the level of NLR-PI, which can be regarded as a more useful prognostic index, exhibited strong predictive power for predicting the prognosis of patients with AC after the PD procedure.

Lignin, as a major by-product of pulp and paper industry, has attracted extensive interest for the preparation of high value-added products, due to the merits of abundant, sustainable, inexpensive, and unique functional groups. This review focuses on the strategies to develop high performance polyurethane (PU) materials from lignin on the basis of main reports, in which lignin was used not only as macromonomer to substitute petroleum-based polyols, but also as blending filler for PU industry. Pre-treatment approaches, especially lignin fractions extracted with various solvents and chemical modifications, e.g., depolymerization, hydroxyalkylation, dealkylation, and esterication, were widely explored to enable lignin more reactive and available to synthesize PU products. In addition, lignin/PU blends were also prepared to fulfill industrial demand. With adjustment of lignin structure, the PU formulation, and synthesis procedures, various lignin-based PU products with advanced properties and a higher bio-substitution ratio have been developed, demonstrating the potential industrial application of lignin for high value-added sustainable materials.

Abstract Background Locally advanced pancreatic cancer (LAPC) remains a challenge for current treatments. Local destructive therapies, such as irreversible electroporation (IRE) and radiofrequency ablation (RFA), were used more and more frequently in the treatment of LAPC. Objective This study aimed to compare the efficacy of IRE with RFA in patients with LAPC. Methods From August 2015 to August 2017, 58 LAPC patients after IRE or RFA therapy, which was performed through open approach, were retrospectively reviewed. The survival outcomes after IRE (36 patients) and RFA (18 patients) were compared after propensity score matching (PSM) analysis. Results Before PSM analysis, IRE after the induction chemotherapy resulted in significant higher overall survival (OS) rates and progression‐free survival (PFS) rates to RFA (2‐year OS, 53.5% vs 30.8%, P = .013; 2‐year PFS, 28.4% vs 12.1%, P = .043). After PSM analysis, compared with RFA, the survival benefit of IRE was even more obvious, (2‐year OS, 53.5% vs 27.0%, P = .010; 2‐year PFS, 28.4% vs 6.4%, P = .018). For patients with tumor larger than 4 cm, IRE resulted in comparable OS and PFS between RFA and IRE while IRE also achieved better long‐term OS to RFA for those with tumor smaller than 4 cm. Multivariate analysis illustrated that IRE was a favorable prognostic factor in terms of OS and PFS in patients with LAPC. Conclusions IRE after induction chemotherapy is superior to RFA after induction chemotherapy for treating LAPC patients while these two therapies have comparable efficacy for tumors which were larger than 4 cm.

BackgroundAccumulating evidence has indicated the vital role of inflammation-based score (IBS) in predicting the prognostic outcome of cancer patients. Otherwise, their value in intrahepatic cholangiocarcinoma (iCCA) remains indistinct. The present study aimed to evaluate whether IBSs were related to survival outcomes in iCCA patients.MethodClinical characteristics were retrospectively collected in 399 patients diagnosed with iCCA from cohorts of Sun Yat-sen University Cancer Center (SYSUCC) and the First Hospital of Dalian Medical University (FHDMU). The survival curves were constructed with the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were conducted to determine the prognostic factors of overall survival (OS) and progression-free survival (PFS). The concordance index and the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) were used to compare the predictive value of inflammation-based scores in terms of survival outcomes.ResultsThe significant survival differences in OS and DFS were observed when patients were stratified by the modified Glasgow Prognostic Score (mGPS) (p

Abstract Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC.

Abstract Background With the increase in cancer survivors, more pancreatic ductal adenocarcinomas (PDACs) are developing as second primary cancers. Whether a prior cancer has an inferior impact on survival outcomes in patients with PDAC remains unknown, and the validity of criteria used to exclude patients with prior cancers in clinical trials needs to be determined. The aim of this study was to evaluate the prognostic factors and assess the survival impact of a prior cancer in patients with second primary PDAC. Methods Patients with PDAC were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific mortality rates were compared between patients with and those without prior cancer. Results The data of 9235 patients with PDAC from 2004 to 2015 were retrieved from the SEER database, consisting of 438 (4.74%) patients with a prior cancer and 8797 (95.26%) patients without a prior cancer, the patients were then pair-matched using propensity score matching (PSM) analysis. The median OS rates were 7 months for both groups of patients with PDAC with and without prior cancer. These two groups of patients had similar survival rates and cancer-specific mortalities before and after the PSM analysis. In the multivariate analysis, a history of prior cancer was not a significant prognostic factor of OS in patients with PDAC. Conclusions Patients with PDAC who had a prior cancer had similar OS and cancer-specific mortality rates as those of patients without a prior cancer. The inclusion of patients with a prior cancer in the clinical trials of PDAC should be considered.

Abstract Background Locally advanced pancreatic cancer (LAPC) represents more than one third of pancreatic cancers and owns poor survival after the standard chemotherapy. Irreversible electroporation (IRE) is a novel method and has been recently used in LAPC. The aim of this study was to compare the efficacy of IRE and radiotherapy after induction chemotherapy for patients with LAPC. Methods From August 2015 to August 2017, a total of 76 patients with biopsy proven LAPC and who had received IRE or radiotherapy after chemotherapy were included. Thirty-two pairs of patients were selected through propensity score matching (PSM) analysis and the efficacy of two treatments was compared. Results Before PSM analysis, after induction chemotherapy, patients with LAPC benefited more in terms of overall survival (OS) and progression free survival (PFS) from IRE, compared with radiotherapy (2-year OS rates, 53.5% vs 26.9%, p = 0.039; 2-year PFS rates, 28.4% vs 13.3%, p = 0.045). After PSM analysis, the survival benefits of OS and PFS of patients after induction chemotherapy followed by IRE were more obvious than those of patients treated with radiotherapy (2-year OS rates, 53.5% vs 20.7%, p = 0.011; 2-year PFS rates, 28.4% vs 5.6%, p = 0.004). Multivariate Cox regression analysis indicated that IRE after induction chemotherapy was identified as a significant favourable factor for both OS and PFS in both the whole and matched cohort. Conclusions Induction chemotherapy followed by IRE is superior to induction chemotherapy followed by radiotherapy for treating LAPC. A randomized clinical trial comparing the efficacy of IRE and radiotherapy after the induction chemotherapy is therefore considerable.

Abstract Background Our objective was to identify risk factors affecting overall survival (OS) and cancer-specific survival (CSS) and build nomograms to predict survival based on a large population-based cohort. Methods Two hundred and thirty patients diagnosed with CHCC between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training cohort. In addition, Ninety-nine patients diagnosed with CHCC between 2000 and 2017 were retrospectively extracted from Sun Yat-Sen University Cancer Center (SYSUCC) as an external validation. Nomograms for predicting probability of OS and CSS were established. Performance of the nomograms was measured by concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). Results In training cohort, the 1-, 2 and 3-year OS were 67.7, 46.8 and 37.9%, and the 1-, 2 and 3-year CSS were 73.1, 52.0 and 43.0%, respectively. The established nomograms were well calibrated in both training and validation cohort, with concordance indexes (C-index) of 0.652 and 0.659, respectively for OS prediction; 0.706 and 0.763, respectively for CSS prediction. Nomograms also displayed better discriminatory compared with 8th edition tumor-node-metastasis (TNM) stage system for predicting OS and CSS. Conclusion We constructed nomograms to predict OS and CSS based on a relatively large cohort. The established nomograms were well validated and could serve to improve predictions of survival risks and guide management of patients with CHCC after surgery.

BackgroundIntrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment.MethodsBetween March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups.ResultsICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort.ConclusionsHAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.

Locally advanced pancreatic cancer (LAPC) is a lethal disease and neoadjuvant chemotherapy and conversional resection is shown to provide the best survival for LAPC patients. Irreversible electroporation (IRE) is a new and effective method for the treatment of LAPC. This study aimed to compare the long-term survival of LAPC patients after neoadjuvant chemotherapy followed by conversional resection and IRE. A total of 140 LAPC patients were included from August 2015 to March 2020. The survival outcomes of patients after treatment with chemotherapy, chemotherapy combined with conversional resection or IRE were analyzed and compared. Patients in these three groups had similar clinical and pathological characteristics. Patients in the resection and IRE groups had similar median OS time (resection group vs. IRE group: 25.3 months vs. 26.0 months, P>0.050), which was significantly longer than that of the chemotherapy group (8.7 months, P

Irreversible electroporation (IRE) is an effective method for treating pancreatic ductal adenocarcinoma (PDAC). It remains unclear whether IRE can induce a specific immune response by stimulating macrophages. Here, the associated markers of macrophages were analyzed after exposure to tumor culture supernatant (TSN) of tumor cells treated with electroporation. Subcutaneous and orthotopic PDAC models were also used to evaluate the effect of macrophage polarization induced by IRE. Aside from its direct killing effect, IRE could induce the immunogenic cell death of tumor cells by increasing the synthesis and secretion of damage associated molecular patterns. Moreover, IRE could increase the release of HMGB1, which activates the MAPK-p38 pathway and leads to the increased expression of M1 markers in macrophages, through binding to the receptor of the advanced glycation end-product (RAGE) receptor. M1 polarization was inhibited by the inhibitors of HMGB1 release, the RAGE receptor, and the MAPK-p38 signaling pathway, but it was activated by rHMGB1 or the stimulator of MAPK-p38. In addition, the promotion of M1 macrophage polarization was enhanced by the positive-feedback release or expression of HMGB1 and RAGE through the MAPK-ERK pathway in macrophages. The promotion of M1 macrophage polarization induced by IRE provided a specific rationale for the combination of IRE and immune therapy in treating PDAC.

Synaptophysin-like 1 (SYPL1) is a neuroendocrine-related protein. The role of SYPL1 in pancreatic ductal adenocarcinoma (PDAC) and the underlying molecular mechanism remain unclarified. Here, after analyzing five datasets (GSE15471, GSE16515, GSE28735, TCGA, and PACA-AU) and 78 PDAC patients from Sun Yat-sen University Cancer Center, we demonstrated that SYPL1 was upregulated in PDAC and that a high level of SYPL1 indicated poor prognosis. Bioinformatics analysis implied that SYPL1 was related to cell proliferation and cell death. To validate these findings, gain-of-function and loss-of-function experiments were carried out, and we found that SYPL1 promoted cell proliferation in vitro and in vivo and that it protected cells from apoptosis. Mechanistic studies revealed that sustained extracellular-regulated protein kinase (ERK) activation was responsible for the cell death resulting from knockdown of SYPL1. In addition, bioinformatics analysis showed that the expression of SYPL1 positively correlated with antioxidant activity. Reactive oxygen species (ROS) were upregulated in cells with SYPL1 knockdown and vice versa. Upregulated ROS led to ERK activation and cell death. These results suggest that SYPL1 plays a vital role in PDAC and promotes cancer cell survival by suppressing ROS-induced ERK activation.

The post-progression survival (PPS) of patients with pancreatic ductal adenocarcinoma (PDAC) after radical resection is varied and influenced by the characteristics of tumor progression. We aimed to establish and validate a nomogram to predict PPS for PDAC patients after surgery. A total of 302 PDAC patients who had undergone curative resection from 2008 to 2018 were enrolled in this study and randomly divided into training and validation cohorts at a ratio of 3:1. The nomogram was established based on independent prognostic factors selected by LASSO and Cox regression and measured by the area under the receiver operating characteristic curve (AUC) and the concordance index (C-index). Significant prognostic factors included carbohydrate antigen 19-9 (CA19-9), lymph node (LN)9 metastasis, LN14 metastasis, LN16 metastasis, tumor differentiation, imaging-detected tumor size, local progression, liver-only metastasis, lung-only metastasis, and multiple metastases. The nomogram built on these factors showed powerful efficacy in PPS prediction, with C-index values of 0.751 (95% CI 0.692–0.0.810) and 0.710 (95% CI 0.645–0.755) for the training and validation cohorts, respectively. The AUC values for the 1-year and 2-year PSS rates were 0.745, 0.747, and 0.783, 0.748, respectively; these values were higher than those of the 8th tumor–node–metastasis (TNM) stage system. The exploration of risk factors and the establishment of a nomogram can provide new versions of personalized recurrence management for PDAC patients after surgery.

Orbital rhabdomyosarcoma (RMS) is a relatively rare primary malignancy occurring in children. The objective of this study was to evaluate the cumulative incidence of cancer-specific death and competing risk of death among RMS patients after surgery and to build nomograms to predict overall survival (OS) and cancer-specific survival (CSS) based on a large population-based cohort. The records of 217 patients who were pathologically diagnosed with an orbital RMS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. The 10-, 20-, and 40-years OS rates and cancer-specific mortality were 82.5, 72.2, and 48.9%, respectively, and 14.8, 21.7, and 21.7%, respectively. The established nomograms were well-calibrated and validated, with a concordance index (C-index) of 0.901 and 0.944 for OS prediction, 0.923 and 0.904, for CSS prediction in the training and validation cohorts, respectively. The values of area under the receiver operating characteristic curve (AUC) for 10-, 20-, and 40-years OS and CSS prediction were 0.908, 0.826, and 0.847, and 0.924, 0.863, and 0.863, respectively. The established nomogram showed relatively good performances and could be convenient individualized predictive tools for prognostic prediction in RMS patients.

Abstract Background Cancer‐associated fibroblasts (CAFs) are among the most prominent cells during the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC). However, CAFs are heterogeneous and the precise origins are not fully elucidated. This study aimed to explore whether monocytes can transdifferentiate into fibroblasts in PDAC and evaluate the clinical significance of this event. Methods CD14+ monocytes were freshly isolated from human peripheral blood. Immunofluorescence, reverse transcription‐quantitative PCR, western blot, flow cytometry and enzyme‐linked immunosorbent assay were used to detect the expression of αSMA, fibronectin, and other relevant molecules. In addition, latex beads with a mean particle size of 2.0 µm were used to assess the phagocytic capacity. Moreover, RNA sequencing (RNA‐seq) was performed to identify the differences induced by H2O2 and the underlying mechanisms. Results Immunofluorescence identified αSMA and fibroblast‐specific protein 1 expression by tumor‐associated macrophages in PDAC. The in vitro experiment revealed that oxidative stress (H2O2 or radiation) induced monocyte‐to‐myofibroblast transdifferentiation (MMT), as identified by upregulated αSMA expression at both the RNA and protein levels. In addition, compared with freshly isolated monocytes, human monocyte‐derived macrophages increased fibronectin expression. RNA‐seq analysis identified p53 activation and other signatures accompanying this transdifferentiation; however, the p53 stabilizer nutlin‐3 induced αSMA expression through reactive oxygen species generation but not through the p53 transcription/mitochondria‐dependent pathway, whereas the p38 inhibitor SB203580 could partially inhibit αSMA expression. Finally, MMT produced a unique subset of CAFs with reduced phagocytic capacity that could promote the proliferation of pancreatic cancer cells. Conclusions Oxidative stress in the tumor microenvironment could induce MMT in PDAC, thus inducing reactive stroma, modulating immunosuppression, and promoting tumor progression. Reducing oxidative stress may be a promising future therapeutic regimen.

Abstract Background Irreversible electroporation is shown to induce immune changes in pancreatic cancer while the histology evidences are still lacking. The aim of this study is to show the immune changes in histology and explore whether irreversible electroporation (IRE) can induce immunogenic cell death (ICD) of tumor cells and activate specific immune responses. Methods Subcutaneous and orthotopic pancreatic cancer models were established and used to evaluate the effect of immune modulation of IRE. The infiltration of T cells was assessed in several tissue samples before and after IRE. Abscopal effect was then assessed by comparing the tumor growth of subcutaneous tumors after in situ ablation with IRE or exposure to tumor culture supernatant (TSN) of IRE‐treated Pan02. The expression of damage‐associated molecular patterns (DAMPs) of tumor cells after IRE was detected in vitro. Results IRE could significantly suppress the tumor growth and increase the infiltration of CD8+ T cells. After ablation with IRE or stimulation with TSN of Pan02 treated by IRE, the growth of untreated tumor was suppressed and the effector CD8+ T cells and memory T cells increased significantly in mice. Additionally, the inhibition effect of tumor growth increased along with the increasing strength levels of electroporation. IRE induced ICD of tumor cells by increasing the synthesis and secretion of DAMPs. Conclusions IRE induced local immunomodulation by increasing specific T cells infiltration. Through enhancing specific immune memory, IRE not only led a complete tumor regression in suit, but also induced abscopal effect, suppressing the growth of the latent lesions.

Irreversible electroporation (IRE) is a novel method which was especially suitable for the treatment of locally advanced pancreatic cancer (LAPC). The purpose of this study was to evaluate probabilities of overall survival (OS) and cancer-specific survival (CSS) in patients with LAPC after IRE treatment and to construct nomograms to predict survival for these patients. Data of patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database and medical records of Sun Yat-sen University Cancer Center (SYSUCC). A total of 312 LAPC patients after IRE treatment were included into this study. The 3-year cumulative incidence of cancer-specific mortality for patients with LAPC after IRE treatment was 74.3%. Nomograms for predicting probabilities of OS, CSS, and non-cancer-specific survival (NCSS) were built and calibrated with the concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). The established nomograms were well-calibrated, with C-indexes of 0.782 for OS prediction, 0.729 for CSS prediction, and 0.730 for NCSS prediction. Compared with the TNM stage system, the established nomograms displayed higher values of AUC and showed better discriminatory power for predicting OS, CSS, and NCSS. These nomograms were well-calibrated and could serve to guide management of LAPC patients after IRE treatment.

Pancreatic adenocarcinoma of the body and tail often has a dismal prognosis and lacks a specific prognostic stage. The aim of this study was to construct a nomogram for predicting survival of patients with pancreatic adenocarcinoma of the body and tail after surgery. Data of patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database and from medical records of Sun Yat-sen University Cancer Center (SYSUCC). In a multivariate analysis for overall survival (OS), the following six variables were identified as independent predictors and incorporated into the nomogram: age, tumor differentiation, tumor size, lymph node ratio (LNR), and chemotherapy. A nomogram was built based on independent risk predictors. The concordance index (C-index) for nomogram, Tumor-Node-Metastasis (TNM) 7th and 8th stage system were 0.775 [95% confidence interval (CI), 0.731–0.819], 0.617 (95%CI, 0.575–0.659), and 0.632 (95%CI, 0.588–0.676), respectively. The calibrated nomogram predicted survival rates which closely corresponded to the actual survival rates. Furthermore, the values of the area under receiver operating characteristic (ROC) curves (AUC) of the nomograms were higher than those of the TNM 7th or 8th stage system in predicting 1-, 2-, and 3-year survival of patients in training and external validation cohorts. The well-calibrated nomogram could be used to predict prognosis for patients with pancreatic adenocarcinoma of the body and tail after surgery.

Locally advanced pancreatic cancer (LAPC) has a dismal prognosis even after standard chemotherapy, and local progression contributes to nearly one-third of the deaths of these patients. As a local destructive method, irreversible electroporation (IRE) can feasibly treat LAPC. The aim of this study was to evaluate IRE combined with chemotherapy as a new treatment and compare its efficacy with that of chemotherapy alone in patients with LAPC. The data of LAPC patients who received chemotherapy with or without IRE were extracted from Surveillance, Epidemiology, and End Results (SEER) database and medical records of Sun Yat-sen University Cancer Center (SYSUCC). The efficacy of these two treatments was compared using propensity score matching (PSM) analysis. LAPC patients treated with the combination therapy had better overall survival (OS). Significantly higher cancer-specific survival (CSS) and progression-free survival (PFS) rates were also observed in patients after IRE combined with chemotherapy, compared with chemotherapy alone. IRE combined with chemotherapy was established as a favorable factor for OS, CSS, and PFS in LAPC patients. This combination method may be a more suitable treatment for patients with LAPC.

Predicting the prognosis of gallbladder carcinoma (GBC) has always been important for improving survival. The objective of this study was to determine the risk factors of survival for patients with GBC after surgery and to develop predictive nomograms for overall survival (OS) and cancer-specific survival (CSS) using a large population-based cohort. We identified 2,762 patients with primary resectable GBC in the Surveillance, Epidemiology, and End Results (SEER) database for the period of 2004 to 2014 and another 152 patients with GBC after surgery from Sun Yat-sen University Cancer Center (SYSUCC) for the period of 1997 to 2017. The 1-, 2-, and 3-year cancer-specific mortalities were 37.2, 52.9, and 59.9%, while the competing mortalities were 5.8, 7.8, and 9.0%, respectively. Nomograms were developed to estimate OS and CSS, and these were validated by concordance indexes (C-indexes) and evaluated using receiver operating characteristic (ROC) curves. The C-indexes of the nomograms for OS and CSS prediction were 0.704 and 0.732, respectively. In addition, compared with the 8th Tumor-Node-Metastasis staging system, the newly established nomograms displayed higher areas under the ROC curves for OS and PFS prediction. The nomograms are well-validated and could thus aid individual clinical practice.

Abstract Background The prognosis of patients with periampullary adenocarcinoma after pancreatoduodenectomy is diverse and not yet clearly illustrated. The aim of this study was to develop a nomogram to predict individual risk of overall survival (OS) and progression-free survival (PFS) in patients with periampullary adenocarcinoma after pancreatoduodenectomy. Methods A total of 205 patients with periampullary adenocarcinoma after pancreatoduodenectomy were retrospectively included. OS and PFS were evaluated by the Kaplan-Meier method. Two nomograms for predicting OS and PFS were established, and the predictive accuracy was measured by the concordance index (Cindex) and calibration plots. Results Lymph node ratio (LNR), carbohydrate antigen 19–9 (CA19–9) and anatomical location were incorporated into the nomogram for OS prediction and LNR, CA19–9; anatomical location and tumor differentiation were incorporated into the nomogram for PFS prediction. All calibration plots for the probability of OS and PFS fit well. The Cindexes of the nomograms for OS and PFS prediction were 0.678 and 0.68, respectively. The OS and PFS survival times were stratified significantly using the nomogram-predicted survival probabilities. Conclusions The present nomograms for OS and PFS prediction can provide valuable information for tailored decision-making for patients with periampullary adenocarcinoma after pancreatoduodenectomy.

Abstract On-chip waveguide amplifiers offer higher gain in small device sizes and better integration with photonic devices than the commonly available fiber amplifiers. However, on-chip amplifiers have yet to make its way into the mainstream due to the limited availability of materials with ideal light guiding and amplification properties. A low-loss nanostructured on-chip channel polymeric waveguide amplifier was designed, characterized, fabricated and its gain experimentally measured at telecommunication wavelength. The active polymeric waveguide core comprises of NaYF4:Yb,Er,Ce core-shell nanocrystals dispersed within a SU8 polymer, where the nanoparticle interfacial characteristics were tailored using hydrolyzed polyhedral oligomeric silsesquioxane-graft-poly(methyl methacrylate) to improve particle dispersion. Both the enhanced IR emission intensity from our nanocrystals using a tri-dopant scheme and the reduced scattering losses from our excellent particle dispersion at a high solid loading of 6.0 vol% contributed to the outstanding optical performance of our polymeric waveguide. We achieved one of the highest reported gain of 6.6 dB/cm using a relatively low coupled pump power of 80 mW. These polymeric waveguide amplifiers offer greater promise for integrated optical circuits due to their processability and integration advantages which will play a key role in the emerging areas of flexible communication and optoelectronic devices.

Recurrence and distant metastases were main reasons of unfavorable outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. The aim of this study was to describe the patterns, timing, and predictors of recurrence or metastasis in PDAC patients after curative surgery. Patients with PDAC who underwent radical pancreatectomy were included. Associations between clinicopathological and radiological characteristics and specific pattern of progression were investigated. Least absolute shrinkage and selection operator (LASSO) and Cox regression were applied to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). A total of 302 patients were included into present study, and 173 patients were documented as recurrence after a median survival of 24.7 months. More than half of patients recurred after 12 months after surgery, and the liver was the most common metastatic site. Decreased time interval to progression, elevated carbohydrate antigen 19-9 (CA19-9) level, and lymph node (LN)16 metastasis were independent predictors for reduced OS. Independent prognostic factors for PFS included elevated carcinoembryonic antigen (CEA) level, local progression, liver or lung-only metastasis, local + distant progression, multiple metastases, LN16 metastasis, imaging tumor size, chemotherapy, and tumor–node–metastasis (TNM) stage. The predictive system showed valuable prediction performance with values of concordance indexes (C-indexes) and the area under the receiver operating characteristic curve (AUC) over 0.80. Different survival curves and predictive factors for specific patterns of disease progression suggested the biological heterogeneity, providing new versions into personal management of recurrence in PDAC patients after surgery.

A polyurethane based thermogelling system comprising poly(ω-pentadecalactone) (PPDL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG), termed as PDEP, was synthesized. The incorporation of PPDL lowers critical micelle concentration (CMC) as well as critical gelation concentration (CGC) of the novel copolymers compared to commercial Pluronic® F127. The thermogels showed excellent thermal stability at high temperature up to 80°C, fast response to temperature change in a time frame of less than second, as well as remarkable self-healing properties after being broken at high strain. In vitro drug release studies using docetaxel (DTX) and cell uptake studies using doxorubicin (DOX) show high potential of the hydrogel as drug reservoir for sustainable release profile of payloads, while the in vivo anti-tumor evaluation using mice model of hepatocellular carcinoma further demonstrated the significant inhibition on the growth of tumor. Together with its excellent biocompatibility in different organs, the novel PDPE thermogelling copolymers reported in this work could potentially be utilized as in situ-forming hydrogels for liver cancer therapy.