Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial.

OBJECTIVE: To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC). METHODS: We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up. RESULTS: The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P < 0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P < 0.05). The absolute neutrophil count was 4.17 ± 0.79 (× 109/L) on day 1 and peaked 6.81 ± 2.37 (× 109/L) on day 10 in the experimental group; the value in the control group was 2.81 ± 0.86 (× 109/L) on day 1. It decreased significantly and reached the minimum 0.91 ± 0.53 (× 109/L) on day 10 (P < 0.05). The experimental group had a lower FN incidence than the control group (P < 0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 months vs. 8.7 months, P = 0.958) or OS (23.9 months vs. 17.3 months, P = 0.325) over an 18.6-month median follow-up time. CONCLUSION: PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.

A randomized phase II study of erlotinib plus nab-paclitaxel versus erlotinib alone as second-line therapy for Chinese patients with advanced EGFR wild-type non-small-cell lung cancer.

Erlotinib is a standard second-line therapy for patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for those patients with epidermal growth factor receptor (EGFR) wild-type (WT) tumors is undecided. In this randomized phase II study, NSCLC patients with EGFR-WT tumors, who had been treated with platinum-based chemotherapy but still developed disease progression, were assigned to receive second-line treatment of erlotinib plus nab-paclitaxel or erlotinib alone. We found PFS and OS were significantly improved by erlotinib plus nab-paclitaxel. The adverse events were also well tolerable.

Memristor-based neural networks: a bridge from device to artificial intelligence.

Since the beginning of the 21st century, there is no doubt that the importance of artificial intelligence has been highlighted in many fields, among which the memristor-based artificial neural network technology is expected to break through the limitation of von Neumann so as to realize the replication of the human brain by enabling strong parallel computing ability and efficient data processing and become an important way towards the next generation of artificial intelligence. A new type of nanodevice, namely memristor, which is based on the variability of its resistance value, not only has very important applications in nonvolatile information storage, but also presents obsessive progressiveness in highly integrated circuits, making it one of the most promising circuit components in the post-Moore era. In particular, memristors can effectively simulate neural synapses and build neural networks; thus, they can be applied for the preparation of various artificial intelligence systems. This study reviews the research progress of memristors in artificial neural networks in detail and highlights the structural advantages and frontier applications of neural networks based on memristors. Finally, some urgent problems and challenges in current research are summarized and corresponding solutions and future development trends are put forward.

In-Depth Physical Mechanism Analysis and Wearable Applications of HfOx-Based Flexible Memristors.

Since memristors as an emerging nonlinear electronic component have been considered the most promising candidate for integrating nonvolatile memory and advanced computing technology, the in-depth reveal of the memristive mechanism and the realization of hardware fabrication have facilitated their wide applications in next-generation artificial intelligence. Flexible memristors have shown great promising prospects in wearable electronics and artificial electronic skin (e-skin), but in-depth research on the physical mechanism is still lacking. Here, a flexible memristive device with a Ag/HfOx/Ti/PET crossbar structure was fabricated, and a remarkable analog switching characteristic similar to synaptic behavior was observed. Through detailed data fitting and in-depth physical mechanism analysis, it is confirmed that the analog switching characteristics of the device are mainly caused by carrier tunneling. Furthermore, the memristive properties of the Ag/HfOx/Ag/PET device can be attributed to the conductive filaments formed by the redox reaction of the active metal Ag. Finally, the interfacial barrier is extracted by the Arrhenius diagram and the energy band diagram, which is drawn to clearly demonstrate the conduction mechanism of charge trapping in the device. Therefore, the HfOx-based flexible memristor with analog switching behavior and stable memory performance lays the foundation for cutting-edge applications in wearable electronics and smart e-skin.

Model integrating CT-based radiomics and genomics for survival prediction in esophageal cancer patients receiving definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (dCRT) is a standard treatment option for locally advanced stage inoperable esophageal squamous cell carcinoma (ESCC). Evaluating clinical outcome prior to dCRT remains challenging. This study aimed to investigate the predictive power of computed tomography (CT)-based radiomics combined with genomics for the treatment efficacy of dCRT in ESCC patients. METHODS: This retrospective study included 118 ESCC patients who received dCRT. These patients were randomly divided into training (n = 82) and validation (n = 36) groups. Radiomic features were derived from the region of the primary tumor on CT images. Least absolute shrinkage and selection operator (LASSO) regression was conducted to select optimal radiomic features, and Rad-score was calculated to predict progression-free survival (PFS) in training group. Genomic DNA was extracted from formalin-fixed and paraffin-embedded pre-treatment biopsy tissue. Univariate and multivariate Cox analyses were undertaken to identify predictors of survival for model development. The area under the receiver operating characteristic curve (AUC) and C-index were used to evaluate the predictive performance and discriminatory ability of the prediction models, respectively. RESULTS: The Rad-score was constructed from six radiomic features to predict PFS. Multivariate analysis demonstrated that the Rad-score and homologous recombination repair (HRR) pathway alterations were independent prognostic factors correlating with PFS. The C-index for the integrated model combining radiomics and genomics was better than that of the radiomics or genomics models in the training group (0.616 vs. 0.587 or 0.557) and the validation group (0.649 vs. 0.625 or 0.586). CONCLUSION: The Rad-score and HRR pathway alterations could predict PFS after dCRT for patients with ESCC, with the combined radiomics and genomics model demonstrating the best predictive efficacy.

Effectivity of involved-field radiotherapy for recurrent brain metastasis in patients with small-cell lung cancer.

Objectives: To investigate the outcome difference of whole brain radiotherapy (WBRT) and involved-field radiotherapy (IFRT) in limited-stage small-cell lung cancer (LS-SCLC) patients with recurrent brain metastases (BMs) after prophylactic cranial irradiation (PCI). Methods: A retrospective analysis was carried out in 68 LS-SCLC patients who underwent WBRT or IFRT owing to the occurrence of recurrent BMs after PCI from 2009 to 2020. Results: The median overall survival (OS) of all patients was 11.43 months [95% confidence interval (CI) 9.39-13.48 months]. In the paired comparison of OS, the IFRT group had a significantly longer survival time than the WBRT group in all patients [17.80 months vs. 8.47 months; hazard ratio (HR), 0.393, 95% CI, 0.213-0.728; P = 0.002] and 46 matched patients (18.23 months vs. 8.73 months; HR, 0.411, 95% CI, 0.195-0.865; P = 0.019). In terms of the intra-cranial progression-free survival (iPFS), there was no significant difference between the WBRT group and IFRT group before matching (5.93 months vs. 7.30 months; HR, 0.644, 95% CI, 0.373-1.112; P = 0.111); similarly, no statistical difference was detected between the WBRT group and IFRT group after matching (5.33 months vs. 8.10 months; HR, 0.623, 95% CI, 0.323-1.199; P = 0.152). Meanwhile, of the 41 patients with symptoms, 27 cases (65.9%) had symptom relief, showing tolerable toxicity without unexpected toxicity during the observation. Conclusions: Compared with WBRT, IFRT exhibits better survival benefits for LS-SCLC patients with recurrent BMs after PCI. Re-irradiation for BMs exhibits advantages of symptom relief and tolerable side effects.

Non-zero-crossing current-voltage hysteresis behavior induced by capacitive effects in bio-memristor.

Capacitive devices have drawn a beautiful application scene in electronic device systems ranging from touch sensors, energy storages and multifunction transistors, but serving as memristive term is still blank. Sweet potato peel (SPP) as function layer was employed to develop the memristive device with Ag/SPP/F-doped SnO2 (FTO) structure. A current-voltage (I-V) hysteresis, which is characterized by a typical capacitive behavior, is impressively observed in the developed device. Nonvolatile data storage is feasible using the non-zero-crossing I-V hysteresis because the resistance states can be well maintained. Charge transfer at the Ag/SPP and SPP/FTO interfaces, and the interplay between Ag+ ions and charges are responsible for this non-zero-crossing I-V hysteresis behaviors. This work possibly gives an insight into the data storage in terms of a new conception electronic device based on environment-friendly material.

A sustainable resistive switching memory device based on organic keratin extracted from hair.

It is the consensus of researchers that the reuse of natural resources is an effective way to solve the problems of environmental pollution, waste and overcapacity. Moreover, compared with the case of inorganic materials, the renewability of natural biomaterials has great prominent advantages. In this study, keratin, which was first extracted from hair due to its high content in hair, was chosen as a functional layer for the fabrication of a resistance switching device with the Ag/keratin/ITO structure; in this device, a stable resistive switching memory behavior with good retention characteristic was observed. Via mechanism analysis, it is expected that there is hopping conduction at low biases, and the formation of a conductive filament occurs at high biases. Furthermore, our device exhibited a stable switching behavior with different conductive materials (Ti and FTO) as bottom electrodes, and the influence of Ag and graphite conductive nanoparticles (NPs) doped into the keratin layer on the switching performance of the device was also investigated. This study not only suggests that keratin is a potential biomaterial for the preparation of memory devices, but also provides a promising route for the fabrication of bio-electronic devices with non-toxicity, degradability, sustainability etc.

Use CT Imaging to Predict the Short-Term Outcome of Concurrent Chemoradiotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma.

OBJECTIVE: To extract the computed tomography (CT) imaging features of the primary lesions in patients with advanced esophageal squamous cell carcinoma (ESCC) and to study whether these imaging features can predict the short-term outcome after concurrent chemoradiotherapy (CCRT). METHODS: From January 2014 to December 2015, a total of 49 patients with locally advanced ESCC who underwent CCRT were analyzed retrospectively. They were randomly categorized into the training and validation groups. Collection of CT imaging of patients before and intermediate stage undergoing radiotherapy. The correlations between imaging characteristics and short-term outcome were analyzed. The accuracy of cutoff value was verified by imaging characteristics of patients in validation group. RESULT: There were 38 patients in the training group and 11 patients in the validation group. 13 patients in the training group were classified as responders and 25 patients as nonresponders. According to the CT imaging before radiotherapy, there are no significant differences between responders and nonresponders. According to the CT imaging in the middle stage of radiotherapy, responders showed significantly higher Roundness than nonresponders (P = .004, 95% confidence interval [CI] = 0.0419-0.212). The areas under the ROC curves for the ability to predict significantly tumor response were 0.768 for Roundness (P = .001, 95% CI = 0.603-0.889). The cutoff value of Roundness is 0.3099. Roundness showed no significant associations with survival parameters. CONCLUSIONS: Computed tomography imaging in the middle stage of radiotherapy can predict the short-term outcome of concurrent chemoradiotherapy for patients with locally advanced ESCC but have no predictive effect on the total survival time.

Two-dimensional Blue-AsP monolayers with tunable direct band gap and ultrahigh carrier mobility show promising high-performance photovoltaic properties.

The successful fabrication of black phosphorene (Black-P) in 2014 and subsequent synthesis of layered black As1-xPx alloys have inspired research into two-dimensional (2D) binary As-P compounds. The very recent success in growing blue phosphorene (Blue-P) further motivated exploration of 2D Blue-AsP materials. Here, using ab initio swarm-intelligence global minimum structure-searching methods, we have obtained a series of novel and energetically favored 2D Blue-AsP (denoted x-AsP, x = I, II, III, IV, V) compounds with As : P = 1 : 1 stoichiometry. They display similar honeycomb structures to Blue-P. Remarkably, the lowest-energy AsP monolayer, namely I-AsP, not only possesses a quasi-direct band gap (2.41 eV), which can be tuned to a direct and optimal gap for photovoltaic applications by in-plane strain, but also has an ultrahigh electronic mobility up to ∼7.4 × 104 cm2 V-1 s-1, far surpassing that of Blue-P, and also exhibits high absorption coefficients (×105 cm-1). Our simulations also show that 30 nm-thick I-AsP sheet-based cells have photovoltaic efficiency as high as ∼12%, and the I-AsP/CdSe heterostructure solar cells possess a power conversion efficiency as high as ∼13%. All these outstanding characteristics suggest the I-AsP sheet as a promising material for high-efficiency solar cells.

A flexible nonvolatile resistive switching memory device based on ZnO film fabricated on a foldable PET substrate.

In this work, a flexible resistive switching memory device based on ZnO film was fabricated using a foldable Polyethylene terephthalate (PET) film as substrate while Ag and Ti acts top and bottom electrode. Our as-prepared device represents an outstanding nonvolatile memory behavior with good "write-read-erase-read" stability at room temperature. Finally, a physical model of Ag conductive filament is constructed to understanding the observed memory characteristics. The work provides a new way for the preparation of flexible memory devices based on ZnO films, and especially provides an experimental basis for the exploration of high-performance and portable nonvolatile resistance random memory (RRAM).

Metal Ions Redox Induced Repeatable Nonvolatile Resistive Switching Memory Behavior in Biomaterials.

The resistance random access memory (RRAM) based on biomaterials has great potential application in the sustainable electronic devices with the advantages of being sustainable, green, and environment-friendly, and it can offer a potential route for developing bio-RRAM devices, which would be a competitive bench in development of multipurpose memory devices. In our work, the banana peel, an ubiquitous useless waste, is introduced as an intermediate insulating material to preparing resistive switching memory device with Ag/Banana peel/Ti structure, in which the superior switching memory performance with a lager high resistance state/low resistance state resistance ratio and long retention characteristics are revealed. Moreover, the coexistence of memristor effect, capacitance effect, and negative differential resistance phenomenon are observed in our device. The repeatable nonvolatile resistive switching memory behaviors are attributed to the redox properties of metal cations contained in biomaterials.

From dead leaves to sustainable organic resistive switching memory.

An environmental-friendly, sustainable, pollution-free, biodegradable, flexible and wearable electronic device hold advanced potential applications. Here, an organic resistive switching memory device with Ag/Leaves/Ti/PET structure on a flexible polyethylene terephthalate (PET) substrate was fabricated for the first time. We observed an obvious resistive switching memory characteristic with large switching resistance ratio and stable cycle performance at room temperature. This work demonstrates that leaves, a useless waste, can be properly treated to make useful devices. Furthermore, the as-fabricated devices can be degraded naturally without damage to the environment.

Tumor suppressor p53 induces miR-15a processing to inhibit neuronal apoptosis inhibitory protein (NAIP) in the apoptotic response DNA damage in breast cancer cell.

This study was aimed to investigate the functional role of miR-15a in breast cancer cells in response to DNA damage and to illustrate the possible potential underlying molecular mechanism(s). Human breast cancer cell lines MCF-7 cells and/or MDA-MB-231 cells were pre-treated with or without bleomycin. Cells were transfected with corresponding vectors. qRT-PCR was used to detect the expression of mRNA or miRNA, and immunoprecipitation and immunoblot analysis were performed to explore the status of protein association. Cell apoptosis was analyzed with flow cytometry. The results showed that neuronal apoptosis inhibitory protein (NAIP) was negatively regulated by p53 in MCF-7 cells, and NAIP expression was still high in bleomycin-treated MCF-7 cells. In addition, we observed that miR-15a expression was regulated by p53, and the effects of miR-15a on DNA damage was also mediated by p53. Furthermore, the results revealed that the cell apoptosis was mediated by miR-15a. Taken together, this study reveals that p53 negatively regulates NAIP expression by targeting miR-15a processing from primary into precursor miRNA in breast cancer.

A Comparative Study of Noninvasive Hypoxia Imaging with 18F-Fluoroerythronitroimidazole and 18F-Fluoromisonidazole PET/CT in Patients with Lung Cancer.

PURPOSE: This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III-IV lung cancer. METHODS: A total of forty-two patients with inoperable stages III-IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The standard uptake values (SUVs) of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia. RESULTS: All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) were seen in tumor, P = 0.022, <0.001. For the patients with different histopathological subtypes, no significant difference of SUV (or T/B ratio) was observed both in 18F-FMISO and 18F-FETNIM in tumor. A significantly different SUV (or T/B ratio) was detected between < = 2cm, 2~5cm, and >5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029), whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707). Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios) in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02). CONCLUSION: 18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer.

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis.

PURPOSE: To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG) PET. METHODS: All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD) and 18F-FDG metabolic tumor volume (VFDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath) was measured in vitro after the xenografts were removed. RESULTS: A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3), 0.61±0.37 cm3 (range,0.15~1.86 cm3), and 1.24±0.53 cm3 (range,0.17~2.20 cm3), respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001) than with VFDG (R = 0.584,P<0.001). CONCLUSIONS: 18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice.

Clinical features and outcome of patients with HIV-negative multicentric Castleman's disease treated with combination chemotherapy: a report on 10 patients.

To investigate the clinical characteristics and outcome of patients with HIV-negative multicentric Castleman's disease (MCD) treated exclusively with combination chemotherapy, and review literature to improve the diagnosis and management of this disease. A retrospective study was performed on the medical records of 10 patients with HIV-negative MCD treated exclusively with combination chemotherapy at one medical institution from May 2004 to April 2012. And relevant clinical, pathological, radiographic, and laboratory data were examined in order to evaluate treatment responses, with symptom onsets and survival period serving as the endpoints of the assessment. All patients have multifocal lymphadenopathy, and the associated system symptoms are found in 80 % of the cases. All patients were treated with lymphoma-based chemotherapy alone. The duration of follow-up ranged from 5 to 77 months for nine patients. Four patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone: One was alive with no evidence of disease, and three were alive with disease. Three patients received cyclophosphamide, vincristine, and prednisone (COP) alone: One remained alive with disease, and two experienced recurrences and passed away. Two had only minimal response to COP and were switched to CHOP, and they were still alive with disease. MCD is a more progressive clinical entity, and long-term follow-up is necessary. CHOP chemotherapy may be an effective treatment option for patients with MCD, whereas when to start chemotherapy, how many cycles of chemotherapy required, and the role of combined radiotherapy remain to be further studied.

FDG PET-CT in non-small cell lung cancer: relationship between primary tumor FDG uptake and extensional or metastatic potential.

OBJECTIVE: To explore the relationships between primary tumor 18F-FDG uptake measured as the SUVmax and local extension, and nodal or distant organ metastasis in patients with NSCLC on pretreatment PET-CT. METHODS: 93 patients with NSCLC who underwent 18F-FDG PET-CT scans before the treatment were included in the study. Primary tumor SUVmax was calculated; clinical stages, presence of local extension, nodal and distant organ metastases were recorded. The patients with SUVmax ≥ 2.5 were divided into low and high SUVmax groups by using the median SUVmax. The low SUVmax group consisted of 45 patients with SUVmax<10.5, the high SUVmax group consisted of 46 patients with SUVmax ≥ 10.5. Their data were compared statistically. RESULTS: 91 cases with SUVmax≥2.5 were included for analysis. The mean SUVmax in patients without any metastasis was 7.42 ± 2.91 and this was significantly lower than that (12.18 ± 4.94) in patients with nodal and/or distant organ metastasis (P=0.000). In the low SUV group, 19 patients had local extension, 22 had nodal metastasis, and 9 had distant organ metastasis. In the high SUV group, 31 patients had local extension, 37 had nodal metastasis, and 18 had distant organ metastases. There was a significant difference in local extension (P =0.016), distant organ metastasis (P =0.046), and most significant difference in nodal metastasis rate (P =0.002) between the two groups. In addition, there was a moderate correlation between SUVmax and tumor size (r = 0.642, P<0.001), tumor stage (r = 0.546, P<0.001), node stage (r = 0.388, P<0.001), and overall stage (r = 0.445, P= 0.000). CONCLUSION: Higher primary tumor SUVmax predicts higher extensional or metastatic potential in patients with NSCLC. Patients with higher SUVmax may need a close follow-up and more reasonable individual treatment because of their higher extensional and metastatic potential.