A machine learning-based risk stratification tool for in-hospital mortality of intensive care unit patients with heart failure.

BACKGROUND: Predicting hospital mortality risk is essential for the care of heart failure patients, especially for those in intensive care units. METHODS: Using a novel machine learning algorithm, we constructed a risk stratification tool that correlated patients' clinical features and in-hospital mortality. We used the extreme gradient boosting algorithm to generate a model predicting the mortality risk of heart failure patients in the intensive care unit in the derivation dataset of 5676 patients from the Medical Information Mart for Intensive Care III database. The logistic regression model and a common risk score for mortality were used for comparison. The eICU Collaborative Research Database dataset was used for external validation. RESULTS: The performance of the machine learning model was superior to that of conventional risk predictive methods, with the area under curve 0.831 (95% CI 0.820-0.843) and acceptable calibration. In external validation, the model had an area under the curve of 0.809 (95% CI 0.805-0.814). Risk stratification through the model was specific when the hospital mortality was very low, low, moderate, high, and very high (2.0%, 10.2%, 11.5%, 21.2% and 56.2%, respectively). The decision curve analysis verified that the machine learning model is the best clinically valuable in predicting mortality risk. CONCLUSION: Using readily available clinical data in the intensive care unit, we built a machine learning-based mortality risk tool with prediction accuracy superior to that of linear regression model and common risk scores. The risk tool may support clinicians in assessing individual patients and making individualized treatment.

Trends in incidence and long-term prognosis of acute kidney injury following coronary angiography in Chinese cohort with 11,943 patients from 2013 to 2017: an observational study.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. METHODS: This retrospective cohort study was based on the registry at Guangdong Provincial People's Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. RESULTS: 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13-1.68; P-value < 0.01, P for trend < 0.01). The temporal trends of incidence among patients of different ages and genders yielded similar findings. During a standardized follow-up of 1 year, 178 (13.7 %) CA-AKI patients died in total, which showed no obvious decreased trend in this 5 five years from 21.1 to 16.5 (adjusted hazard ratio [aHR], 0.72; 95 %CI, 0.36-1.45; P-value = 0.35, P for trend = 0.24). CONCLUSIONS: Our Chinese cohort showed that the incidence of CA-AKI increased significantly, while CA-AKI associated mortality showed no obvious decreased trend in the last five years. Our findings support more active measures to prevent CA-AKI and improve the prognosis of CA-AKI patients.

Urolithin B suppresses tumor growth in hepatocellular carcinoma through inducing the inactivation of Wnt/ß-catenin signaling.

Consumption of dietary ellagitannins (ETs) has been proven to benefit multiple chronic health disorders including cancers and cardiovascular diseases. Urolithins, gut microbiota metabolites derived from ETs, are considered as the molecules responsible for these health effects. Previous studies have demonstrated that urolithins exhibit antiproliferative effects on prostate, breast, and colon cancers. However, as for hepatocellular carcinoma (HCC), it remains elusive. Herein, we aim to investigate the function of urolithin B (UB), a member of urolithins family, in HCC. The effects of UB on cell viability, cell cycle and apoptosis were evaluated in HCC cells, and we found UB could inhibit the proliferation of HCC cells, which resulted from cell cycle arrest and apoptosis. Furthermore, UB could increase phosphorylated ß-catenin expression and block its translocation from nuclear to cytoplasm, thus inducing the inactivation of Wnt/ß-catenin signaling. Using a xenograft mice model, UB was found to suppress tumor growth in vivo. In conclusion, our data demonstrated that UB could inhibit the proliferation of HCC cells in vitro and in vivo via inactivating Wnt/ß-catenin signaling, suggesting UB could be a promising candidate in the development of anticancer drugs targeting HCC.

Aerobic oxidative acylation of nitroarenes with arylacetic esters under mild conditions: facile access to diarylketones.

A facile and regioselective base-mediated aerobic oxidative acylation of nitroarenes to access diarylketones under mild conditions has been developed. It features the use of bench-stable and readily available arylacetates as acyl surrogates, and the absence of transition-metals and synthetic oxidants. This protocol involves a cascade CDC/oxidative decarboxylation process.

Effect of Retrogression with Different Cooling Ways on the Microstructure and Properties of T'/η' Strengthened Al-Zn-Mg-Cu Alloys.

Retrogression and re-aging (RRA) treatment has been proven to effectively overcome the trade-off between strength and corrosion resistance. Current research focuses on the heating rate, temperature, and holding time of retrogression treatment while ignoring the retrogression cooling ways. In this paper, the effects of RRA treatment with different retrogression cooling ways on the microstructure and properties of newly developed T'/η' strengthened Al-Zn-Mg-Cu alloys were investigated by performing tests on mechanical properties, intergranular corrosion (IGC) resistance, and electrochemical corrosion behavior. The results show that the mechanical properties of samples subject to RRA treatment with water-quenching retrogression (ultimate tensile strength, yield strength, and elongation of 419.2 MPa, 370.2 MPa, and 15.9, respectively) are better than those of air-cooled and furnace-cooled samples. The corrosion resistance of water-quenching (IGC depth of 162.2 µm, corrosion current density of 0.833 × 10-5 A/cm2) and furnace-cooled samples (IGC depth of 123.7 µm, corrosion current density of 0.712 × 10-5 A/cm2) is better than that of air-cooled samples. Microstructure characterization reveals that the effect of the retrogression cooling rate on mechanical properties is related to the size of T'/η' precipitates with grains as well as the proportion of T' and η', while the difference in corrosion resistance depends on the continuity of grain boundary precipitates (GBPs). With mechanical properties, corrosion resistance, and time cost taken into consideration, it is appropriate to select water quenching for retrogression. These findings offer valuable insights for further design to achieve superior performance in various applications.

Pericardial Delivery of SDF-1α Puerarin Hydrogel Promotes Heart Repair and Electrical Coupling.

The stromal-derived factor 1α/chemokine receptor 4 (SDF-1α/CXCR4) axis contributes to myocardial protection after myocardial infarction (MI) by recruiting endogenous stem cells into the ischemic tissue. However, excessive inflammatory macrophages are also recruited simultaneously, aggravating myocardial damage. More seriously, the increased inflammation contributes to abnormal cardiomyocyte electrical coupling, leading to inhomogeneities in ventricular conduction and retarded conduction velocity. It is highly desirable to selectively recruit the stem cells but block the inflammation. In this work, SDF-1α-encapsulated Puerarin (PUE) hydrogel (SDF-1α@PUE) is capable of enhancing endogenous stem cell homing and simultaneously polarizing the recruited monocyte/macrophages into a repairing phenotype. Flow cytometry analysis of the treated heart tissue shows that endogenous bone marrow mesenchymal stem cells, hemopoietic stem cells, and immune cells are recruited while SDF-1α@PUE efficiently polarizes the recruited monocytes/macrophages into the M2 type. These macrophages influence the preservation of connexin 43 (Cx43) expression which modulates intercellular coupling and improves electrical conduction. Furthermore, by taking advantage of the improved "soil", the recruited stem cells mediate an improved cardiac function by preventing deterioration, promoting neovascular architecture, and reducing infarct size. These findings demonstrate a promising therapeutic platform for MI that not only facilitates heart regeneration but also reduces the risk of cardiac arrhythmias.

An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty.

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti-stenosis drug-eluting stents face challenges due to their limited functions and long-term safety concerns, significantly compromising their therapeutic effect. Herein, a stent-free anti-stenosis drug coating (denoted as Cur-NO-Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor-peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur-NO-Gel has the capability to release NO upon ß-galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur-NO-Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur-NO-Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Effect of Lattice Constants and Precipitates on the Dimensional Stability of Rolled 2024Al during Isothermal Aging.

The change in material dimensional will lead to the decline of instrument accuracy and reliability. In this paper, the characterization and analysis of the lattice constant, precipitates, and dislocation density of the material by X-ray diffraction (XRD) and transmission electron microscopy (TEM) reveals the reason why the relative dimensional change in the rolled 2024Al is one order of magnitude lower than that of the as-cast 2024Al during isothermal aging. Compared with as-cast 2024Al, the dislocation density of rolled 2024Al is higher, the lattice constant decreases less before and after aging, and the precipitates have orientation and more content, resulting in the dimensional change in rolled 2024Al being smaller than that of as-cast 2024Al. In addition, two main reasons for decreasing the dimensional change in rolled 2024Al are discussed: the decrease in lattice constant, the formation and growth of the S phase before and after aging.

Effect of Interfacial Strength on Mechanical Behavior of Be/2024Al Composites by Pressure Infiltration.

In this paper, two kinds of Be/2024Al composites were prepared by the pressure infiltration method using two different beryllium powders as reinforcements and 2024Al as a matrix. The effect of interfacial strength on the mechanical behavior of Be/2024Al composites was studied. Firstly, the microstructure and mechanical properties of the two composites were characterized, and then the finite element analysis (FEA) simulation was used to further illustrate the influence of interfacial strength on the mechanical properties of the two Be/2024Al composites. The mechanical tensile test results show that the tensile strength and elongation of the beryllium/2024Al composite prepared by the blocky impact grinding beryllium powder (blocky-Be/2024Al composite) are 405 MPa and 1.58%, respectively, which is superior to that of the beryllium/2024Al composite prepared by the spherical atomization beryllium powder (spherical-Be/2024Al composite), as its strength and elongation are 331 MPa and 0.38%, respectively. Meanwhile, the fracture of the former shows brittle fracture of beryllium particles and ductile fracture of aluminum, while the latter shows interface debonding. Further FEA simulation illustrates that the interfacial strength of the blocky-Be/2024Al composite is 600 MPa, which is higher than that of the spherical-Be/2024Al composite (330 MPa). Therefore, it can be concluded that the better mechanical properties of the blocky-Be/2024Al composite contribute to its stronger beryllium/aluminum interfacial strength, and the better interfacial strength might be due to the rough surface and microcrack morphology of blocky beryllium particles. These research results provide effective experimental and simulation support for the selection of beryllium powder and the design and preparation of high-performance beryllium/aluminum composites.

Influence of Interface on Mechanical Behavior of Al-B4C/Al Laminated Composites under Quasi-Static and Impact Loading.

In this study, Al-B4C/Al laminated composites with high interlayer bonding strength were fabricated by integrated hot-pressed sintering accompanied with hot rolling. The mechanical properties and interface behavior of the Al-B4C/Al laminated composites were investigated under quasi-static and impact loading. The results show that the Al-B4C/Al laminated composites obtain a high interface bonding strength, because no interlayer delamination occurs even after fractures under quasi-static and impact loads. The Al-B4C/Al laminated composites exhibit a better comprehensive mechanical performance, and the fracture can be delayed due to the high bonding strength interface. Moreover, laminated composites can absorb more impact energy than the monolithic material under impact loading due to the stress transition and relaxation.

A Novel Multi-Scale Ceramic-Based Array (SiCb+B4Cp)/7075Al as Promising Materials for Armor Structure.

Ceramic panel collapse will easily lead to the failure of traditional targets. One strategy to solve this problem is to use separate ceramic units as armor panels. Based on this idea, we propose an aluminum matrix composite using pressure infiltration, containing an array of ceramic balls, the reinforcement of which consists of centimeter-scale SiC balls and micron-scale B4C particles. Three different array layouts were designed and fabricated: compact balls in the front panel (F-C), non-compact balls in the front panel (F-NC), and compact balls inside the target (I-C). The penetration resistance properties were tested using a 12.7 mm armor-piercing incendiary (API). The results show that there are no significant internal defects, and the ceramic balls are well-bonded with the matrix composite. The F-NC structure behaves the best penetration resistance with minimal overall damage; the I-C structure has a large area of spalling and the most serious damage. Finite element simulation reveals that the ceramic balls play a major role in projectile erosion; in the non-compact structure, the composite materials between the ceramic balls can effectively disperse the stress, thereby avoiding the damage caused by direct contact between ceramic balls and improving the efficiency of ceramic ball erosion projectiles. Furthermore, it is essential to have a certain thickness of supporting materials to prevent spalling failure caused by stress wave transmission during penetration. This multi-scale composite exhibits excellent ballistic performance, providing valuable insights for developing anti-penetration composite armor in future applications.

Computed tomography appearance of inflammatory myofibroblastic tumor in the mediastinum.

OBJECTIVE: This study aimed to improve the diagnosis of inflammatory myofibroblastic tumor (IMT) in the mediastinum by analysis of computed tomographic (CT) images. MATERIALS AND METHODS: Clinical data, CT, and pathological findings of 6 patients diagnosed with IMT in the mediastinum were retrospectively analyzed. RESULTS: Of the 6 patients, 5 were women, and mean age at diagnosis was 34 years. All the lesions were solid soft tissue masses and ranged in maximum diameter from 5.0 to 8.5 cm, which were located in the anterior (n = 1), middle (n = 2), and posterior mediastinum (n = 3). The anterior mediastinal tumor had a clear boundary. The tumors in the middle mediastinum had indistinct boundaries: one was invading the right wall of the trachea and the other was invading the esophageal wall. A tumor located in the right posterior mediastinum caused osteolysis of the adjacent ribs. A small amount of calcification was seen in the tumor in the right posterior-inferior mediastinum. After administration of contrast, all tumors showed varying degrees of contrast enhancement (range, 17-47 HU) on chest CT scan. Recurrence occurred in only 1 case. CONCLUSIONS: The common CT appearance of IMT in the mediastinum is as a soft tissue mass with uniform density. All tumors show varying degrees of contrast enhancement. Some lesions have clear boundaries; others do not. Computed tomography examination can help to determine the areas involved by lesions and their relationships with adjacent tissues, which facilitates the prediction of the likely surgical requirements.

Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis.

BACKGROUND: Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. Our objective was to describe the clinical manifestations, diagnosis, and management of primary pulmonary cryptococcosis in immunocompetent patients. METHODS: We retrospectively reviewed the clinical data of 76 patients with primary pulmonary cryptococcosis who were admitted to our hospital from 1995 to 2010. RESULTS: Pulmonary cryptococcosis was pathologically proven in all patients. Mean patient age was 42.5 years and 55 patients (72%) were male. The major clinical manifestations were cough (47 pts, 62%), expectoration (29 pts, 38%), fever (16 pts, 21%), chest pain (15 pts, 20%), dyspnea (17 pts, 22%), and emaciation (10 pts, 13%). Eighteen patients (24%) were asymptomatic. Most patients were admitted due to shadows on chest X-rays. Lesions were more common in the lower lung (60 pts, 78.9%) than in the upper lung (25 pts, 32.9%). More lesions (28 pts, 37%) were characterized by patchy consolidations. Pulmonary cryptococcosis was confirmed histologically among all patients. Surgical removal of lesions or treatment with fluconazole and other antifungal agents for complete courses led to favorable outcomes for most patients. CONCLUSIONS: Primary pulmonary cryptococcosis was found mainly in immunocompetent patients aged <50 years without preexisting lung disease. Shadow on the chest X-ray is the predominant feature. Treatment with a complete course of fluconazole and/or other antifungal agents can achieve favorable outcome.

The efficacy of the inhalation of an aerosolized Group A streptococcal preparation in the treatment of lung cancer.

OBJECTIVE: To observe the efficacy of the inhalation of an aerosolized group A streptococcal (GAS) preparation in treating orthotopic lung cancer in mouse models and assess the feasibility, safety, and effectiveness of this administration mode for lung cancer. METHODS: Lewis lung carcinoma (LLC) cell strains were administered via intrathoracic injection to establish orthotopic lung cancer mouse models. After the tumor-bearing models were successfully established, as confirmed by computed tomography, the mice were administered by inhalation with an aerosolized GAS preparation (GAS group) or aerosolized normal saline (control group). The anti-tumor effect of the aerosolized GAS preparation was evaluated histologically; meanwhile, the survival and quality of life were compared between these two groups. RESULTS: The aerosolized GAS preparation showed remarkably anti-tumor effect, causing the necrosis of the orthotopic lung cancer cells in tumor-bearing mice. Furthermore, mice in the GAS group had significantly better quality of life and longer survival than those in control group. CONCLUSIONS: The inhalation of aerosolized GAS preparation may be a feasible, safe and effective solution for lung cancer.

The expression of p33(ING1), p53, and autophagy-related gene Beclin1 in patients with non-small cell lung cancer.

The purpose of this study was to investigate the expressions of tumor inhibitor of growth (ING1) gene p33ING1, p53, and autophagy-related gene Beclin1 in human non-small cell lung cancer (NSCLC), and the correlation between their expressions with clinical pathological features and clinical significance. The research can provide new ideas and experimental evidence for early diagnosis and biotherapy for NSCLC in the future. The human NSCLC tissues and surrounding non-cancerous tissues were collected from surgical operation. The expressions of mRNA or protein of p33ING1, p53, and Beclin1 were detected by using of reverse transcription polymerase chain reaction or Western blot in these tissues. The results were used to analyze the relationships between these gene expressions with the developing of NSCLC and clinical pathological features. The expressions of mRNA or protein of p33ING1 and Beclin1 in NSCLC tissues were significantly lower than that in surrounding noncancerous tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in well- and middle-differentiated NSCLC tissues were lower than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in presence of lymph nodes metastasis were lower than those in absence of lymph nodes metastasis (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in patients of pathological stage (stages I-II) were higher than those in pathological stage (stages III-IV) (p < 0.05). But the expression of protein of mutant-type p53 in NSCLC tissues was significantly higher than that in surrounding non-cancerous tissues (p < 0.05). The expressions of protein of mutant-type p53 in well- and middle-differentiated NSCLC tissues were higher than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of protein of mutant-type p53 in presence of lymph nodes metastasis were higher than those in absence of lymph nodes metastasis (p < 0.05). The expressions of protein of mutant-type p53 in patients of pathological stage (stages I-II) were lower than those in pathological stage (stages III-IV) (p < 0.05). These expression changes of p33ING1, p53, and autophagy-related Beclin1 genes were associated with tumor cell differentiation, lymph nodes metastasis, and pathological stage of NSCLC. But these expression changes of these three genes were not associated with gender, age, size of primary carcinoma, histological type of NSCLC (p > 0.05). The expression of mRNA of p53 and Beclin1 were correlated with p33ING1 mRNA expression in NSCLC tissues (p < 0.05). The activity changes of tumor inhibitor of growth, autophagy, and apoptosis may be related to the emergence and the development of NSCLC. The combined detection of p33ING1, p53, and Beclin1 genes and proteins will be helpful for early diagnosis and prognosis judgment for NSCLC, and can provide experimental evidence for biotherapy of NSCLC.

Prognostic impact of MMP-2 and MMP-9 expression in pathologic stage IA non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to assess the value of matrix metalloproteinase (MMP)-2 and MMP-9 expression and other potential prognostic factors in predicting the clinical outcome of patients after definitive surgery for pathologic stage IA non-small cell lung cancer (NSCLC). METHODS: One hundred and forty-six consecutive and non-selected patients who underwent definitive surgery for stage IA NSCLC were included in this study. Formalin-fixed paraffin-embedded specimens were stained for MMP-2 and MMP-9, which were statistically evaluated for their prognostic value and other clinicopathological parameters. RESULTS: Of the 146 patients studied, 102 (69.9%) cases were classified as having high expression for MMP-2. A total of 89 carcinomas (61.0%) had high expression for MMP-9. MMP-9 expression correlated with Eastern Cooperative Oncology Group (ECOG) performance status, pT stage, and differentiation (P = 0.005, <0.001, and <0.001, respectively). Vessel invasion, pT stage, and MMP-9 expression maintained their independent prognostic influence on overall survival (P = 0.037, <0.001, and <0.001, respectively). CONCLUSIONS: From results of our relatively large database, MMP-9 may be considered as a viable biomarker that can be used in conjunction with other prognostic factors such as vessel invasion and pT stage to predict the prognosis of patients with completely resected pathologic stage IA NSCLC.

Correction: Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy.

Correction for 'Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy' by Chenxing Fu et al., Nanoscale, 2020, 12, 12126-12132, DOI: .

[Follicular dendritic cell sarcoma: a clinicopathologic analysis of ten cases].

OBJECTIVE: To study the clinicopathologic features of follicular dendritic cell sarcoma (FDCS) and its differential diagnosis. METHODS: Ten cases of FDCS were studied by light microscopy, immunohistochemistry and in-situ hybridization. The clinical features and follow-up information were analyzed. RESULTS: Amongst the 10 cases of FDCS studied, the male-to-female ratio was 1:1. The mean age of the patients was 42 years. Six of them were located in cervical and peritoneal lymph nodes and four in extranodal sites (including tonsil, pelvic cavity, tail of pancreas and spleen). Histologically, the tumor cells had whorled, storiform or diffuse growth patterns. They were spindle in shape and contained syncytial eosinophilic cytoplasm, with round or oval nuclei, vesicular chromatin, distinct nucleoli and a variable number of mitotic figures. Multinucleated tumor giant cells and intranuclear pseudoinclusions were occasionally seen. There was a sprinkling of small lymphocytes and neutrophils within the tumor as well as in the perivascular region. Immunohistochemical study showed that the tumor cells were diffusely or focally positive for CD21, CD23, CD35 and D2-40, but negative for LCA, CD20, CD3, CD1a, HMB45 and CK. Some of them showed EMA, CD68 and S-100 reactivity. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed positive signals in only one case (which was diagnosed as inflammatory pseudotumor-like FDCS). Of the 7 patients with follow-up information available (duration: 2 months to 39 months; mean: 14 months), 2 cases with paraneoplastic pemphigus died of pulmonary infection at 5 and 7 months respectively. The remaining 5 patients were alive and disease-free after surgical excision (+/- chemotherapy and radiotherapy). CONCLUSIONS: FDCS is a rare low to intermediate-grade malignant tumor. Appropriate application of FDC markers, such as CD21, CD35 and D2-40, would be helpful for arriving at a correct diagnosis. Most cases are associated with good prognosis after surgical treatment, with or without chemotherapy and radiotherapy. Patients with paraneoplastic pemphigus carry a less favorable prognosis.

Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy.

Protein quality control and proteostasis are essential to maintain cell survival as once disordered, they will trigger endoplasmic reticulum (ER) stress and even initiate apoptosis. Severe ER stress-mediated apoptosis is the cause of neurodegenerative diseases and expected to be a new target for cancer therapy. In this study, we designed a small molecule of 1-Nap to execute furin-instructed molecular self-assembly for selectively inhibiting the growth of MDA-MB-468 cells in vitro and in vivo. According to the results of transmission electron microscopy (TEM) and HPLC tracing analysis, 1-Nap is capable of self-assembling upon furin-instructed cleavage that transforms 1-Nap nanoparticles to 1-Nap nanofibers. Fluorescence imaging and Western-blot analysis results indicate that the furin-instructed self-assembly of 1-Nap rather than its ER-targeting interaction is indispensable for the ER stress and activation of apoptosis. The furin-instructed self-assembly of 1-Nap is associated with both the ER (1-Nap's targeting location) and the trans-Golgi network (furin's location); this inspired us to reasonably believe that the blocking of ER-to-Golgi traffic in the secretory pathway by molecular self-assembly may be the intrinsic motivation for controlling cell fate. This work provides a new way for the targeted disturbance of the proteostasis of cells through molecular self-assembly for developing cancer therapeutics.