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Decentralization mechanism provides manufacturers and distributors with greater customization and flexibility they need through IoT-based Industrial Collaboration Systems (IoT-ICS), but it has brought forward security concerns about the shared data-processing tasks and IoT-based access to services and resources. To address them, we propose a practical blockchain solution to achieve decentralized policy management and evaluation on Attribute-based Access Control (ABAC). By offloading the responsibility of ABAC policy administration and decision-making to blockchain nodes, a blockchain-based access control framework, called Policychain, is presented to ensure policy with high availability, autonomy, and traceability. To deliver a solid design, we first present a transaction-oriented policy expression scheme with a well-defined syntax and semantics. The scheme can translate ABAC policies into the blockchain transactions with JavaScript Object Notation (JSON) syntax and Script-based logical expression. We further realize a script-driven policy evaluation by extending blockchain inherent scripting instructions to support attribute acquisition of ABAC entities. Furthermore, we propose a policy lifecycle management scheme from policy creation, renovation, to revocation, in which policies are verified by three validation principles at the transaction level. Finally, we provide sophisticated analysis and experiments to show that our framework is secure and practical for decentralized policy management on ABAC in IoT-ICS.

BACKGROUND Intestinal failure-associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid-gut microbiota (BA-GM) axis contributes to the development of IFALD. AIMS To review the BA-GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. METHODS We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. RESULTS The BA-GM axis demonstrates a unique IF signature manifesting as an increase in primary-to-secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA-GM axis showed promising potential in the management of IFALD. CONCLUSIONS Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA-GM axis may provide optimal clinical benefits and requires future investigation.

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.

Fully integrated voltage regulators (FIVRs) can improve the performance and reduce the power consumption of a system-on-chip (SoC) by providing point-of-load voltage regulation with dynamic voltage scaling. The desirable attributes of FIVRs include high power efficiency, high power density, and fast transient response, which are difficult to achieve due to on-chip area constraint and parasitic effects. Low-quality and low-density on-chip inductors and capacitors are currently the main performance-limiting factors. This article presents a switched-inductor-capacitor (SIC) voltage converter that can operate more efficiently with compact on-chip air-cored metal-tracked inductors than existing step-down voltage converters. The SIC converter consists of an inductor, a flying capacitor, and three power switches, and it can provide fine-grained voltage regulation by using pulsewidth-modulation (PWM) control. The unique SIC converter topology eases the on-chip inductor integration by positioning the inductor at the input power supply and reducing the current stress of the inductor. A proof-of-concept fully integrated SIC voltage regulator is fabricated in a 65-nm CMOS process, with an area of 1.3 mm $\times $ 0.5 mm excluding pads. The output voltage can be regulated from 0.6 to 0.9 V given a 1.2-V input power supply. The output voltage ripple is below 56 mV over the entire range of output voltages and load currents. The peak power efficiency is 78% at an output of 0.9 V and 406 mA. The peak power density is 730 mW/mm2, and the peak current density is 820 mA/mm2.

Limited treatment options are available for relapsed or refractory diffuse large B cell lymphoma (RR DLBCL). Few clinical studies have reported the use of Ibrutinib, a covalent Bruton Tyrosine kinase (BTK) inhibitor, in RR DLBCL. There are relatively few clinical studies about Ibrutinib in RR DLBCL now. We retrospectively investigated the safety and efficacy of Ibrutinib (alone or in combination with other drugs) in patients with RR DLBCL. We reviewed the medical records of 40 RR DLBCL patients who received Ibrutinib alone or in combination with other drugs in our hospital from June 2018 to August 2020. The objective response rate (ORR) of RR DLBCL patients on Ibrutinib was 22.5%. The median progression free survival time (PFS) was 13.0 months (95% CI 8.914–17.086), and the median overall survival time (OS) was 15.0 months (95% CI 11.931–18.089). Rash (25.0%) and fatigue (25.0%) were the most common adverse reactions in this study. The application of Ibrutinib to patients with RR DLBCL has good short-term efficacy, and the adverse reactions are well tolerated. Combined treatment of Ibrutinib with other drugs has been found to more effective than Ibrutinib therapy alone.

Recently, the spatial-temporal data of urban moving objects, e.g., cars and buses, are collected and widely used in urban trajectory exploratory analysis. Urban bus service is one of the most common public transportation services. Urban bus data analysis plays an important role in smart city applications. For example, data analysts in bus companies use the urban bus data to optimize their bus scheduling plan. Map services providers, e.g., Google map, Ten-cent map, take urban bus data into account to improve their service quality (e.g., broadcast road update instantly). Unlike urban moving cars or pedestrians, urban buses travel on known bus routes. The operating buses form the "bus flows" in a city. Efficient analyzing urban bus flows has many challenges, e.g., how to analyze the dynamics of given bus routes? How to help users to identify traffic flow of interests easily? In this work, we present CheetahVIS, a visual analytical system for efficient massive urban bus data analysis. CheetahVIS builds upon Spark and provides a visual analytical platform for the stakeholders (e.g., city planner, data analysts in bus company) to conduct effective and efficient analytical tasks. In the demonstration, demo visitors will be invited to experience our proposed CheetahVIS system with different urban bus data analytical functions, e.g., bus route analysis, public bus flow overview, multiple region analysis, in a real-world dataset. We also will present a case study, which compares different regions in a city, to demonstrate the effectiveness of CheetahVIS.

Traditional centralized access control has some shortcomings in robustness, trustworthiness and circulation. Blockchains have the advantages of fault tolerance and trust. Smart contracts have the characteristics of automatic execution and flexible expansion. Tokens can well record credential information and transfer easily. In this paper, blockchain, smart contract and token are integrated and applied to access control to solve the shortcomings of traditional access control. First, access control, blockchain, smart contract and token are briefly described. Second, this paper proposes a solution by giving the general data structure of access control token, elaborating the equivalence, split, merge and verification algorithms of access control token, and explaining the system architecture of token-based access control. Last, this paper uses a token-based access control simulation system to verify that token-based access control has certain comparative advantages in robustness, trustworthiness, circulation, concurrency and so on.

Purpose Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit tumour angiogenesis. In the present study, we evaluated the efficacy and safety of apatinib for patients with RR DLBCL. Patients and methods In this phase II, open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two-stage design. All patients were administered apatinib at an initial dose of 500 mg on a 4-week cycle at home and visited the outpatient clinic every two cycles to evaluate efficacy and to record adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), and overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.). Results From January 2017 to February 2019, we screened 35 patients and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses, and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate of 71.9%. The median PFS and OS were 6.9 (95% confidence interval [CI], 5.8-7.9) and 7.9 months (95% CI, 7.0-8.7), respectively. The median DoR was 5.0 months (95% CI, 3.5-6.5) for patients who achieved PR. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%), and leucopenia (6.3%). No apatinib-related deaths were noted. Conclusion Home administration of apatinib shows promising efficacy and manageable AEs in patients with RR DLBCL.

Older adults want to remain independent with dignity for as long as possible, especially the solitary older adults. Activity recognition plays an essential role in elderly care and rehabilitation by detecting activity shifts among the elderly population. Despite over a decade of research and development in activity recognition, accurate and reliable systems for older adults in use are few. We propose an automatic data collecting and labeling system by addressing the annotation issue, and a novel coarse-to-fine activities of daily living(ADLs) recognition algorithm for older adults, by combining supervised and unsupervised machine learning methods. The automatic data collecting and labeling system targets at the annotation issue caused by the diversity of ADLs in free-living situations. Multiple sensors fusion strategy is employed to interpret and annotate the ADLs. Leveraging supervised and unsupervised machine learning methods, we can discover and recognize ambulatory and trivial ADLS for older adults. The performance of the automatic data collecting and labeling system is double-checked in a four days long test. With the reliable ground truth, we evaluate the coarse-to-fine ADLs recognition algorithm. The performance of our algorithm is promising, the recognition accuracy is larger than 91%.

This paper presents a dual-output switched-capacitor voltage regulator (DOSCVR) with a new flying capacitor crossing technique (FCCT) to improve power efficiency. With the FCCT, the power loss of the DOSCVR is reduced by 28%, increasing the power efficiency by 7% compared with the power efficiency of the conventional method that generates two voltages using independent single-output SCVRs. This enhanced efficiency results in no area penalty since the total flying capacitance remains unchanged. A prototype is then implemented in a 0.13- $\mu \text{m}$ CMOS process to validate the proposed scheme. The prototype simultaneously produces two regulated voltages of 0.44 and 0.88 V from an input voltage of 1.5 V. The output voltages are regulated by low-bound regulation with frequency modulation. The maximum output current is 12 mA with a total flying capacitance of 0.98 nF, and the measured peak efficiency is 78%.

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed (600 mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT after the end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age. Results: A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD, and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR, 3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia (10.0%). Conclusions: Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes, providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

The study of spectral polarization characteristics of different materials is benefit to improve the abilities of object recognition and polarization remote sensing applications. Most of studies focus on the degree of polarization of the material, the polarized reflectance factor is rarely reported. In this study, we measure the spectral polarized reflectance factor of typical rough coating materials (green and black paint) in the range of 400–900 nm. The polarization reflectance characteristics of coating materials have been analyzed based on the measured data sets and the polarization mechanism. Moreover, a polarized reflectance parameter model is built with the basic of the Kubelka-Munk theory, and the optimal model parameters are fitted by the genetic algorithm. The analyses indicate that our measured polarized reflectance factors of the rough coating samples are spectrally neutral, and the distribution of the polarized reflectance factor is obviously anisotropic. The polarized reflectance parameter model provides good fits to the measurements, which confirms the validity and reliability of the modeling, and can precisely describe the polarization reflectance behaviors of rough coating materials. We also found that contrast between the rough coating samples and typical natural background in polarized reflectance factor is much greater than in degree of linear polarization in visible and near-infrared bands, which suggests that it is more helpful to distinguish the objects in natural environment by using the polarized reflectance factor indicator. The study has a great potential for object identification and polarization scene modeling.

Capacitorless (CL) low-dropout regulators (LDO) have gained significant research interest for point-of-load voltage regulation without off-chip capacitors. While analog CL-LDOs can deliver superior power supply rejection (PSR), digital CL-LDOs are more scalable and efficient. To achieve the advantages of both types, this paper presents a digital CL-LDO with an analog PSR enhancer, delivering strong PSR without compromising scalability and efficiency. Load regulation is performed by an asynchronous digital feedback controller for fast transient response and scalable load drivability. PSR is achieved by a load-insensitive wide-bandwidth analog controller. A prototype chip of the analog-assisted digital CL-LDO is fabricated in a 130-nm CMOS process with an active area of 0.0645 mm2 , supporting load current up to 50 mA at nominal 1-V input and 0.8-V output. The measured PSR is better than –20 dB for frequencies up to 10 MHz, and the measured current efficiency peaks at 99.3%, with average current efficiency of 96.7% across 50× load range. The measured transient response to a full load step, with two values of load capacitance (100 pF and 10 nF), demonstrates the LDO's stable operation over a wide range of load resistance and capacitance.

Purpose To compare the efficacy of rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) with traditional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimens in double-hit lymphoma (DHL) and gene copy number gain (CNG) lymphoma and to contrast the prognosis of these two disease types. Methods We retrospectively examined 127 cases of newly diagnosed diffuse large B-cell lymphoma (DLBCL), and used fluorescence in situ hybridization (FISH) to detect genetic abnormalities in MYC, BCL2, and BCL6. Results In the two schemes, the 2-year progression-free survival (PFS) was higher for R-DA-EPOCH group than for R-CHOP (79.8% vs 57.5%, P=0.002), this advantage was also reflected in 2-year overall survival (OS) (81.6% vs 58.5%, P=0.002). In double CNG patients, R-DA-EPOCH regimen was significantly better than R-CHOP (P=0.007 for PFS, P=0.010 for OS), and R-DA-EPOCH has the same advantage in DHL patients (P=0.001 for PFS, P=0.047 for OS). For the two disease types, the PFS for DHL was inferior to that for double CNG (52.9% vs 72.4%, P=0.008), while the OS was not significantly different (P=0.050). Subgroup analysis showed that the PFS for double CNG with MYC and BCL2 was superior to that for DHL with MYC and BCL2 (P=0.043), this trend is also seen in double CNG and DHL with MYC and BCL6 (P=0.036). However, the OS was not significantly different between the two subgroups. Multivariate analyses showed that in DLBCL patients with genetic abnormality detected by FISH, the treatment and disease types were independent prognostic factors. The adverse reaction rates were similar in R-DA-EPOCH and R-CHOP (P>0.05). Conclusion Our retrospective study shows that DHL has a poorer prognosis than double CNG. Based on its improved lifetime and good tolerance, R-DA-EPOCH is a promising regimen for DHL or double CNG, which is expected to become the first-line treatment for high-risk DLBCL types based on more clinical research.

Imperfect lightness conditions usually lower the visual quality of an image by bringing in unclear image details and poor image contrast. Traditional low-light enhancement models based on one single input are often limited in avoiding the effect of over-enhancement or under-enhancement. Models based on fusing multiple input sources usually perform well in relieving this issue, as they can harmonize the complementary visual appearances of a same scene provided by different sources. Nevertheless, these models still have difficulty in dealing with the situation that only one input is at hand, which usually happens in many practical situations. In this paper, we propose a low-light enhancement model that artificially enriches input sources and then seamlessly fuses them. Specifically, with an input image, we first generate multiple enhanced images based on a lightness-aware camera response model. These images are then fused at mid-level based on a patch-based image decomposition model. To validate our model, we conduct qualitative and quantitative comparisons with several state-of-the-art single-source and multi-source models on a collection of real-world images. Experimental results show that our model better improves the image quality in terms of visual naturalness and aesthetics.

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.

Lijun Du, Lei Zhang, Ling Li, Xin Li, Jiaqin Yan, Xinhua Wang, Xiaorui Fu, Zhenchang Sun, Xudong Zhang, Zhaoming Li, Jingjing Wu, Hui Yu, Yu Chang, Zhiyuan Zhou, Feifei Nan, Xiaolong Wu, Li Tian, Mingzhi Zhang Department of Oncology, Zhengzhou University First Affiliated Hospital, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Mingzhi ZhangDepartment of Oncology, Zhengzhou University First Affiliated Hospital, Lymphoma Diagnosis and Treatment Center of Henan Province, &Ngr;o. 1 Jianshe East Road, Zhengzhou, Henan, People’s Republic of ChinaTel +86 13838565629Fax +86 37166295563Email mingzhi_zhang1@163.comAbstract: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is a specific subtype of peripheral T cell lymphoma (PTCL) with a poor prognosis. To date, there exist no standard therapeutic regimens for relapsed/refractory (R/R) ENKTL. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R ENKTL. Herein, we present three R/R ENKTL patients who failed prior therapies (L-asparaginase containing chemotherapy, radiotherapy or biological-cell therapy, etc.) benefited from the combination regimen comprised of anti-programmed-death-1 (PD-1) antibody toripalimab, chidamide, etoposide, and thalidomide. They received the treatment regimen continuously until the disease progression occurs. As of data collection, two patients achieved complete remission (CR) after 4, 6 cycles of treatment, respectively, and another patient was evaluated as partial remission (PR) after 2 cycles. Treatment-related adverse events (AEs) mainly presented grade 2∼ 3 leukocytopenia and anemia, which were controllable. It follows that PD-1 antibody, chidamide, etoposide, and thalidomide (PCET) regimen may be a promising choice for patients with R/R ENKTL and warrants further investigation.Keywords: NK/T-cell lymphoma, relapsed/refractory, PD-1, chidamide, targeted treatment

Aim: CD19 chimeric antigen receptor (CAR) T cells have been approved by the US FDA for treatment of relapsed and refractory (R/R) B-cell malignancies. Patients & methods: This study investigated the safety and efficacy of autologous 4-1BB costimulatory domain-engineered CD19 CAR-T cells in R/R B-cell lymphoma. Results: After CD19 CAR-T-cell infusion, severe cytokine release syndrome occurred in 28.6% (4/14) of the patients. The overall response rate was 77% with complete remission observed in 6/14 patients at 3 months. A higher tumor burden and grade 3–4 of myelosuppression after chemotherapy were associated with severe cytokine-release syndrome. Notably, combining CD19 CAR-T cells and PD-1 blockade, but not CD19 CAR-T cells alone, reduced intracranial tumor burden in a patient with central invasion of lymphoma. Conclusion: CD19 CAR-T cells could effectively induce tumor remission and PD-1 blockade might improve the efficacy in Chinese patients with R/R B-cell lymphoma.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Aim: To compare the outcomes of GDPT [gemcitabine (G), cisplatin (D), prednisone (P), thalidomide (T)] versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL (peripheral T-cell lymphoma). Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT (77 cases) and CHOP (76 cases) groups. Patients in each group were further divided into four subgroups: PTCL, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL), angioimmunoblastic T cell lymphoma (AITL), and other types subgroup, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3, and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, progression-free survival (PFS), and overall survival (OS) were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The overall response rate (ORR) of the GDPT group was better than that of the CHOP group (66.3% versus 50.0%, p = 0.042), as was the complete remission (CR) rate (42.9% versus 27.6%, p = 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% versus 53.0% for PFS, p = 0.035; 66.8% versus 53.6% for OS, p = 0.039). In the GDPT group, the difference in CR between the four subgroups was statistically significant ( p = 0.046). In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( p Conclusion: The GDPT group had better response rates and prolonged patient PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Trial registration: This open randomized prospective clinical trial was registered at ClinicalTrials.gov (NCT01664975).

Introduction: T lymphoblastic leukemia/lymphoma (T-ALL/LBL) is highly aggressive. Although intensive chemotherapies such as ALL-type regimens are commonly used, about half patients eventually relapse and die of T-ALL/LBL. Chimeric antigen receptor (CAR) T cells have given rise to breakthroughs in treating B cell hematological malignancies. However, there are few clinical studies of CAR-T on T cell malignant tumors. CD7, overexpressed in up to 100% of relapsed/refractory T-ALL/LBL, is an attractive therapeutic target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL). Although several healthy donor derived CD7-CAR-T trials have been reported, autologous CD7-CAR-T cell therapy represents another promising strategy. In current study, a nanobody derived autologous CD7-CAR-T with a highly optimized structure and a clinically feasible strategy to overcome CAR-T cell fratricide and exclude abnormal T cell contamination have been developed. Method This is a single-arm, open label, safety and efficacy pilot study (NCT04004637). Study participants will receive Flu/Cy pre-treatment before CAR-T infusion. CD7 CAR-T was then administered at a single dose of 1.0x10 6 (N=5) or 1.5x10 6 (N=1; Pt#1) or 2x10 6 (N=3; Pt#7, 8,) CAR-T cells/kg. Adverse events were categorized by NCI-CTCAE V5.0. Tumor responses were assessed based on the 2014 Lugano Evaluation Criteria for Lymphoma and 2016 Chinese Guideline for Diagnosis and Treatment of Acute Lymphoblastic Leukemia. Results: Total of 8 patients including 5 r/r T-ALL/LBL and 3 r/r ETP-ALL/LBL (case 4, 5, 6) were assigned to receive CD7 CAR-T cell and completed the efficacy assessment. Overall response rate at 1 month was 100%. In patients followed up for ≥ 3 months, complete remission (CR) rate at 3 month was 75%. Case 1-6 was administered at 1.0×10 6 CAR-T/Kg except for case 1 (1.0×10 6 CAR-T/Kg). Bone marrow (BM) tumor burden of case 1 decreased from 70.03% to 19.51% and case 1 has an OS for nearly two years. Case 2 died due to abdominal infection at 3 month although he was still in MRD- status then. Case 3 had sustained MRD- for 7 months but appeared MRD+ in BM at 8 month, so second CD7 CAR-T infusion had been performed and achieved CR at 14th day again. Case 4 has been achieving CR 12 months. Case 5 and 6 had a DOR (Duration of response) of about 3 and 2 months respectively. In case 1-6, despite case1-2 appeared grade 2 CRS, all other cases only had grade 1. Therefore, in order to further explore the best effective dose, case 7-8 had received dose of 2.0×10 6 CAR-T/Kg. Case 8 are still in complete remission. Unfortunately, case 7 relapsed at 6 month due to CD7 negative blasts. The absence of CD7 on the cell surface enables the tumor to evade CAR T cell-mediated recognition and clearance, despite continued persistence of CAR-T cells. Conclusions: Autologous CD7 CAR-T represents a promising immunotherapy for r/r T-ALL/LBL and exhibited encouraging clinical efficacy and safety in treating r/r T-ALL/LBL and ETP-ALL/LBL. Figure 1Figure 1. Disclosures No relevant conflicts of interest to declare.

Background T cell acute lymphoblastic leukemia and T cell acute lymphoblastic lymphoma (T-ALL/LBL) is a highly aggressive hematological tumor characterized by immature lymphoblasts invading the bone marrow. Treatment options for patients with T-ALL/ LBL are currently limited. Chimeric antigen receptor (CAR)- T cell therapy has opened an era in the treatment of B-cell malignancies. However, the development of CAR-T therapy for T-ALL/LBL faces many challenges. One of them is that therapeutic targets are usually expressed on both tumor and normal T cells, which causes the potential risk of "cell fratricide". Therefore, the difficulty of manufacturing CAR T cells for T-ALL/LBL is dramatically increased. CD7, is 40kD membrane-bound glycoprotein majorly expressed on peripheral T-cells and NK cells and their precursors. CD7 is highly expressed in almost all T-ALL/LBL and considered to be one of the most promising targets for T-ALL/LBL treatment. Patients and Methods This study is based on a phase I clinical trial (NCT04004637) for patients with relapse/refractory CD7 + NK/T cell lymphoma and T-ALL/LBL. To manufacture CAR-T cells, the peripheral blood mononuclear cells (PBMC) were collected from the patients who met the enrollment criteria. The proportion of viability and the ratio of the T cell markers were analyzed. Subsequently, the isolated T cells were co-transduced with CD7 protein expression blocker (PEBL) and CD7-CAR lentiviruses to obtain CD7-CAR-T cells, which can avoid the fratricide of CD7-CAR-T cells. Before the infusion, the phenotypic characteristics and cytotoxicity of CD7-CAR-T products were analyzed. Then peripheral blood (PB) of patients was collected regularly after receiving treatment to analyze the immunophenotyping of T cells. Results From August 2019 to June 2021, 24 leukopaks from patients with CD7-positive T-ALL/LBL were collected, and a total of 32 batches of CD7-CAR T cells were manufactured, with a 78.13% (25/32) successful rate. Among the 7 batches of failure cases, one patient had undergone blood collection twice and CAR-T preparation for three times, but all of three attempts failed (brown icon). Another four patients failed to prepare once. Eight patents were recruited for CD7-CAR-T treatment and 87.5% of complete remission (CR) rate was achieved (7/8), of which a patient (P4, blue icon) has been maintaining CR for more than 15 months. Two other patients, P7 (red icon) and P8 (light red icon), had CD7 - relapse at the time of 6th month and 3rd month after CR, respectively. We divided all samples into successful preparation group (GS), infusion group (GI) and preparation failure group (GF). As shown in Fig. 1A, all three groups exhibited good viability of PBMC. There was no significant difference between GS and GF, but GI was higher than that of GF. The proportion of CD3 + cells in PBMC of GS was significantly lower than that of GF, and GI also showed this feature. Meanwhile, GS and GI both have a higher CD4 +/CD8 + ratio compared with GF. The immunophenotyping results showed CD7-CAR-T products had a majority of the central memory subsets (T CM; 69.41 ± 10.71%) and effect memory subsets (T EM; 28.56 ± 10.19%), with limited number of effector T cell (T E) and naive T cells (T N) (Fig. 1B). The percentage of CAR +CD8 +CD27 + and CD4 +CD25 +CD127 - subsets associated with T cells activation and proliferation, as well as CD223 + and CD279 + subsets related to T cells suppression and exhaustion were lower, except for CD366 + subgroup that also indicated depletion signal (Fig. 1B). In addition, CD7-CAR-T cells showed strong cytotoxicity against CEM (CD7 +) tumor cells accompanied by the release of cytokines, in which the level of IL-2 is extremely low (Fig. 1C). Subsequently, we performed statistics on the proportion of CD3 + and CD4 +/CD8 + cells in the PB of patients after infusion. The proportion of CD3 + cells in the PB of the P4 has been maintained at a high level, and the ratio of CD4 +/CD8 + keeps low (Fig. 1D). P7 showed a significant decrease in the amount of T cells on the 60th day after CAR T infusion, while the ratio of CD4 +/CD8 + showed an upward trend. Conclusion The results indicate that the success rate of CD7-CAR-T manufacturing is positively correlated with higher viability, lower CD3 + and higher CD4 + of PBMC. There was no significant difference among P4 (CR more than 15 months), P7 (CD7 - relapse at 6 th month after CR) and P8 (CD7 - relapse at 3rd month after CR). Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Wave energy is one of the most promising renewable energy sources. The approaches for wave energy harvesting have been attracting more and more attentions all over the world. Although triboelectric nanogenerators (TENGs) based on liquid-solid interface have offered a new method for wave energy harvesting, some challenges still remain such as the relatively low energy power density and energy conversion efficiency. Here, we introduce a liquid-solid generator with electrode arrays that allows for improved wave energy harvesting compared to conventional TENG. The design of 3D electrodes above dielectric layer engenders a bulk effect that connect the electrode array, the polymer layer and bulk water into a closed-looped system. The arrayed generator can also be assembled easily and the instantaneous output power density can be enhanced from 2.7 W/m2 to 11.7 W/m2 with the 3D electrodes. We envision that this bulk effect generator based on liquid-solid interface will open new insight in blue energy harvesting in the future.

Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in the development of cancer. By using the next generation HiSeq sequencing assay, we determined lncRNAs exhibiting differential expression between DLBCL patients and healthy controls. Then, RT-qPCR was performed for identification in clinical samples and cell materials, and lncRNA PANDA was verified to be down-regulated in DLBCL patients and have considerable diagnostic potential. In addition, decreased serum PANDA level was correlated to poorer clinical outcome and lower overall survival in DLBCL patients. Subsequently, we determined the experimental role of lncRNA PANDA in DLBCL progression. Luciferase reporter assay and chromatin immunoprecipitation assay suggested that lncRNA PANDA was induced by p53 and p53 interacts with the promoter region of PANDA. Cell functional assay further indicated that PANDA functioned as a tumor suppressor gene through the suppression of cell growth by a G0/G1 cell cycle arrest in DLBCL. More importantly, Cignal Signal Transduction Reporter Array and western blot assay showed that lncRNA PANDA inactivated the MAPK/ERK signaling pathway. In conclusion, our integrated approach demonstrates that PANDA in DLBCL confers a tumor suppressive function through inhibiting cell proliferation and silencing MAPK/ERK signaling pathway. Thus, PANDA may be a promising therapeutic target for patients with DLBCL.

Compound Dyakonov modes supported by a symmetric uniaxial-isotropic-uniaxial planar structure are investigated, of which the uniaxial layers have the identical principal values of the relative permittivity tensor and optic axis orientation. By solving the canonical boundary-value problem, two branches of compound Dyakonov modes are obtained with symmetric and antisymmetric field distributions respectively. The shapes of the field distributions are proven to be closely related to the reflectance of TE polarized waves at the interfaces of the structure. The relevant characteristics of propagation constants, field distributions, propagation direction ranges and polarization states are numerically calculated. The results show that these characteristics are highly affected by the thickness and the permittivity of the middle isotropic layer, the antisymmetric modes will cutoff when the thickness decreases below critical value and the polarization states of symmetric modes will vary significantly from Dyakonov surface waves due to the strong coupling.

Overshoot and undershoot resulted from line/load/reference change can degrade the power efficiency of a voltage regulator. A pulse width modulation (PWM) skipping technique is thus proposed to reduce such voltage fluctuation. A four-phase interleaved buck converter is experimented to verify the merits of the proposed technique. In steady-state operation, all four phases of the buck converter are driven by a PWM controller to regulate the output voltage. During transient response, the PWM-skipping technique bypasses the PWM controller to drive some phases of the buck converter into charging or discharging state. Simulation results demonstrate that the proposed PWM-skipping technique effectively reduces overshoot and undershoot by more than 25% when the buck converter responds to line/load/reference change.

This paper details our image inpainting solutions of the IEEE ICME 2019 Grand Challenge on Learning-Based Image Inpainting. Specifically we utilize two different methods to fill in the holes in natural images. While both of them are based on the generative adversarial networks, one method fills it in one step and another one solves it progressively. Based on the masking patterns we find in testing data, we propose an approach that divides a cropped image with size 256×256 into 16 squares just like a chessboard and masks some squares to create the training data. To fill the religions in the testing images, we use the same strategy to crop the chessboard-like patches with size 256×256 that cover several masks to feed the trained models. We submit the results with 72 test images and PSNR is 32.2932dB and SSIM is 0.9793.

Background T-lymphoblastic lymphoma (T-LBL) is a highly aggressive neoplasm of lymphoblasts of T-cell origin. Although promising improvements have been recently achieved, one third of patients experience relapse or refractory T-LBL. Therefore, optimal strategies for identifying high-risk patients are urgently needed. Materials and Methods In the present study, 75 newly diagnosed adult patients (aged ≥15 years) with T-LBL were identified and the predictive value of complete blood count (CBC) abnormalities, including lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) on clinical outcomes, was analyzed. Results Using the receiver operating characteristic curve to determine the best cutoff values based on survival, it was found that patients with T-LBL with LMR ≤2.8, NLR ≥3.3, and PLR ≥200 had both inferior progression-free survival (PFS) and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0–2 subgroup. In the multivariable analysis, NLR ≥3.3 together with age >40 years and central nervous system (CNS) involvement were identified to be independently associated with shortened PFS, whereas PLR ≥200 and CNS involvement were identified to be independent risk factors for OS. LMR, NLR, and PLR were integrated to generate a “CBC score” model, which well separated adult patients with T-LBL into three risk groups, and the 3-year OS was 84%, 53%, and 30% for low-, intermediate-, and high-risk patients, respectively. Conclusion Overall, a “CBC score” model was initially promoted for stratification in adult patients with T-LBL using simple, widely available, and easy to interpret parameters in the largest adult T-LBL cohort to date. Implications for Practice Optimal strategies for identifying high-risk patients with T-lymphoblastic lymphoma (T-LBL) are urgently needed. In the largest adult T-LBL cohort to date, simple, inexpensive, widely available parameters were applied and revealed that patients with lymphocyte-monocyte ratio (LMR) ≤2.8, neutrophil-lymphocyte ratio (NLR) ≥3.3, and platelet-lymphocyte ratio (PLR) ≥200 had both inferior progression-free survival and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0–2 subgroup. LMR, NLR, and PLR were integrated to generate a “complete blood count score” model, in which the 3-year OS was 84%, 53%, and 30% for low-, intermediate-, and high-risk patients, respectively.

Colorectal cancer (CRC) is the fourth most lethal malignancy and is the second most common cause of cancer-associated mortality worldwide. The development of high-throughput sequencing has enabled the identification of potential biomarkers for the diagnosis and treatment of various types of cancer. Although microRNA-101 (miR-101) has been demonstrated to be a potential biomarker of CRC, its detailed mechanisms remain to be fully discovered. In the present study, overall survival analysis was applied to determine the association between miR-101 and CRC prognosis. Reverse transcription-quantitative PCR (RT-qPCR) was used to examine gene expression levels in tissues and cells. Cell proliferative and apoptotic activities were determined by MTT and flow cytometry assays, respectively. Wound healing and Transwell assays were used to examine CRC cell migration and invasion, respectively. In the present study, RT-qPCR analysis indicated that miR-101 was significantly downregulated in CRC tissues and cells. However, clinical data collected from The Cancer Genome Atlas revealed no significant association between the expression levels of miR-101 and the prognosis of CRC. Additionally, miR-101 inhibited the progression of CRC by directly binding to the 3'-untranslated region of Ras-related protein Rap1b (Rap1b). This was associated with downregulation of Rap1b expression. Furthermore, the overexpression of Rap1b promoted miR-101 mimic-attenuated CRC cell progression. The present study demonstrated that miR-101 may be involved in the repression of the CRC progression by forming a negative feedback loop with Rap1b. The findings revealed the interaction between miR-101 and Rap1b during the progression of CRC, which could aid the development of therapeutic strategies.

With the rapid development of the mobile Internet, social media dominated by Sina Weibo have become increasingly important in people’s lives, thus the problem of credibility of social network information has come behind. As spread of rumors will bring a series of great harm, rumors detection is particularly important. Therefore this paper proposes a C-GRU model for rumors detection which combines convolutional neural network and gated recurrent unit networks. Our model firstly vectorizes the rumor events, then utilizes CNN to automatically construct the features of the rumor microblogs, and uses GRU to mine temporal information between associated microblogs under rumor events. The experimental results show that C-GRU model outperforms a series of classic models and is as well as superior to individual CNN or GRU.

Purpose To investigate the midterm efficacy and prognostic evaluation of patients with diffuse large B-cell lymphoma (DLBCL) by three image analysis methods: International Harmonization Project (IHP), Deauville 5-Point Scale (5-PS) and Δ SUVmax criteria in 18F-FDG PET/CT. Methods This was a retrospective analysis of 141 patients with DLBCL. All patients were given 3–4 cycles of chemotherapy and 18F-FDG PET/CT. According to three criteria, the patients were divided into negative and positive groups, respectively. Statistical methods were used to assess the midterm efficacy and prognosis factors. Results During the midterm follow-up, a total of 109 people achieved CR. Three methods showed statistically significant differences in OS and PFS for the interim PET/CT, and Δ SUVmax criterion was an independent risk factor for the prognosis of DLBCL patients. Conclusion In our research, IHP, 5-PS and Δ SUVmax criteria all had a significant predictive value, while Δ SUVmax criterion had more advantages in evaluating the midterm efficacy and predicting prognosis for patients with DLBCL in interim PET/CT. But it should be noticed that Δ SUVmax criterion needs more strict guidelines in multicenter trials. The optimal cutoff value of Δ SUVmax% we recommended was 81.54%, which helped to judge the midterm efficacy.

Objective:To evaluate the safety, efficacy, and feasibility of rituximab, fotemustine, pemetrexed and dexamethasone (R-FPD) regimen for primary central nervous system lymphoma (PCNSL) patients. Methods:A prospective, single-center, single-arm, phase II clinical trial. Patients with newly diagnosed PCNSL diagnosed from the First Affiliated Hospital of Zhengzhou University from July 2018 to July 2020. R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100mg/m2 i.v. on D1) ,pemetrexed (600mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1).(NCT04083066) Results: 30 patients were included. After two cycles, the objective response rate(ORR) was 96.4%(27/28,26 PR,1 CR,0 SD,0 PD,2 Censored),the disease control rate(DCR) was 96.4%(27/28); After four cycles, the ORR was 71.4% (15/21, 5PR,10 CR,1SD,5PD,7NR,2 Censored),DCR was 76.2%(16/21). The median progression-free survival (PFS) was 20.3 months (95%CI:5.2--35.4),The median overall survival (OS) was 22.0 months (95%CI:16.1-27.9).The grade III-IV toxicities were mainly leukopenia(17.9%), thrombocypenia(25%) and anemia(10.7%). Conclusion: Fotemustine-based in combination with Rituximab chemotherapy can improve outcomes with the progress free survival and the overall survival benefits, as well as with better tolerability for newly diagnosed PCNSL patients. Keywords: rituximab; primary central nervous system lymphoma; pemetrexed; fotemustine; efficacy Disclosures No relevant conflicts of interest to declare.

3026 Background: CD7 represents a potential target for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL). We developed CD7 nanobody derived chimeric antigen receptor T-cells (CD7-CART), and established a non-gene editing strategy by anchoring CD7 in the ER and/or Golgi to overcome the CART fratricide. Methods: This single-arm, open-label, phase I study is to investigate CD7-CART cell manufacturing feasibility without contamination of malignant T cells, and the safety and efficacy of the CART on patients with CD7 positive relapsed/refractory T-ALL/T-LBL. 3 subjects, identified as both CD4 and CD8 negative T-ALL or T-LBL were enrolled. CART cells were manufactured by using CD4+/CD8+ sorted T cells from leukapheresis. All patients (Pts) were pretreated with Flu/Cy prior to CART infusion. 1x106/kg CART cells were given to case 2 and 3, while 1.5x106/kg to case 1. Results: Case 1 was diagnosed as refractory ALL with myeloid differentiation, who had received intensive chemotherapy and allogeneic hematopoietic stem cell microtransplantation. Case 2 was diagnosed as ALL (T/B mixed type) but relapsed with CNS involvement, and received radiotherapy in addition to intensive chemotherapy. Prior to CART infusion, case 2 had no abnormal B cells but 17.69% of abnormal early T cellsfrom BM. Case 3 had stage VI of T-LBL, which recurred after multi-cycle chemotherapy of BFM-90 regimen and autologous SCT. After CART treatment, no neurotoxicity was observed in all pts. Case 1 had grade 3 CRSwhile case 2 and 3 had grade 1, although increased IL-6 was detected in all pts. Significant CART expansion and persistence were observed in case 2 and 3, and MRD negative CR was confirmed on day 28 in both pts. The number of generalized lymphadenopathy, lymph node size, and the degree of metabolism were all significantly reduced in case 3. Case 1 had only moderate CART expansion, but abnormal early T cells from BM decreased from 70.03% to 19.57% on day 30. After CART infusion, the number of peripheral abnormal T cells became either undetectable in case 2 and 3, or significantly decreased in case 1. Interestingly, CART had unsustained effect on normal T cells in all pts. As of Feb-10-2020, case 1 has 5 months of OS, including 3 months of PFS. Case 2 and 3 has reached 2 and 1 months of PFS and is still in remission. Conclusions: CD7-CART cells can be manufactured without contamination of malignant T cells. CD7-CART therapy is well-tolerated and has great therapeutic potential for relapsed/refractory CD7 positive T cell malignancies. Clinical trial information: NCT04004637 .

8018 Background: Peripheral T-cell lymphoma(PTCL) is highly heterogeneous invasive NHL.There is no consensus standard treatment for it now. So outcomes of GDPT versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL were compared. Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT group (77 cases) and CHOP group (76 cases). Patients in each group were further divided into four subgroups: PTCL-NOS, ALCL, AITL, and an other types, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3 and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, PFS and OS were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The ORR of the GDPT group was better than that of the CHOP group (66.3%vs. 50.0%, P= 0.042), as was the CR rate (42.9% vs. 27.6%, P= 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% vs. 53.0% for PFS, P= 0.035; 66.8% vs. 53.6% for OS, P= 0.039).In the GDPT group, the difference in CR between the four subgroups was statistically significant (P = 0.046).In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( P= < 0.001 and P= 0.005, respectively).There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup( P= 0.015; P= 0.003; P= 0.005, respectively).The data also showed a significant difference in OS among the four subgroups within the GDPT group ( P= 0.001).The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( P= 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3 and TOP2A. Conclusions: The GDPT group had better response rates and prolonged the patients’ PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Clinical trial information: NCT01664975 .

Background and objective Over decades of research and development in vessel segmentation, accurate and reliable methods targeting at pathological vessels are few. Addressing this challenge, we try to delineate the vessel boundary accurately with the presence of pathologies. Methods A novel segmentation framework is presented in this work, a vessel axis tracking algorithm + a patch-based sparse representation. The patch-based algorithm is navigated by the vessel axis tracking algorithm. Within the training process, multi-scale training samples have been used, which has the potential to be both physiologically accurate and computationally effective. The redundant information embedded in the multi-scale training samples is employed to delineate the pathological vessel accurately. To further reduce the computational burden caused by the patch-based sparse representation, a multi-scale dictionary has been generated, and adaptive weights have been assigned to the scale-specific sub-dictionary atoms, for computational efficiency. Results Our method is evaluated by comparing with two state-of-the-art methods, on synthetic complex-structured datasets and real clinical datasets. The performance of our method is promising over the evaluation, since the overlap ratios of our method are high over all the datasets, around 91%, much better than two state-of-the-art methods.

We propose and analyse a novel electro-optically tunable racetrack dual microring resonator with a high Q factor based on a lithium niobate-on-insulator. Using the transfer matrix method, the field transmission and attenuation of the resonator are comparatively investigated to obtain optimised coupling parameters. The enhanced Q value at the resonant wavelength of the inner ring can reach 3.873 × 10 6 , and the blue shift of the resonant wavelength is approximately 16 nm when the applied voltages fall in a ± 150 V range resulting in an electro-optic tuning rate of 0.0526 nm/V. The designed resonator presented here exhibits high performance and may offer more potential applications for lithium niobate nanophotonic devices.

Background Vitamin D with a serum 25(OH)D concentration above 100 nmol/l was associated with disease remission in patients with IBD and suggested that targeted administration may be an anti-inflammatory drug. This study was designed to assess the effectiveness, safety, and predictive measures of a vitamin D regimen in postoperative patients with Crohn’s disease to achieve the above goals. Methods In a prospective study, patients with Crohn’s disease and serum 25(OH)D concentrations Results Thirty-two postoperative patients with Crohn’s colitis had an average 25(OH)D concentration of 51.5 (range 25–74 nmol / L). 25 patients reached the target level and six patients reached 90–94 nmol / L. Because of the reoperation, one patient withdrew in 6 months. Patients with BMI Conclusion Specific oral vitamin D regimens can successfully and safely reach or approach target levels, improve symptom-based activity scores, but do not alter objective indicators of intestinal or systemic inflammation. A modified version of this dose-escalation protocol is suitable for randomised placebo-controlled trials, and the further randomised controlled trial was needed.

Background Single-incision laparoscopic surgery (SILS) with enhanced recovery after surgery (ERAS) can reduce operation trauma and accelerate postoperative rehabilitation. This study aims to investigate the safety and feasibility of SILS with ERAS in the treatment of Crohn’s disease. Methods Thirty patients with Crohn’s disease were randomly assigned to receive traditional laparoscopic surgery plus ERAS (n = 20) and SILS plus ERAS (n = 18)，respectively. Comparisons and analysis were made between the two groups in the perioperative conditions. Results There were significant differences in the mean operation time between the two groups (p < 0.01)，There were no significant differences in the intra-operative blood loss, postoperative complications rates, the time to first flatus and treatment cost (p > 0.05). There were significant differences in the postoperative hospital stay between the two groups (p < 0.05). WBC, CRP and PCT in SILS plus ERAS group were lower than those in the control group at the first days and the third days after operation, the differences were statistically significant (p < 0.05). Conclusion SILS plus ERAS can shorten postoperative hospital stay and facilitate bowel function recovery in the treatment of Crohn’s disease. It is worthwhile to mention the nice cosmetic benefits of SILS, the perioperative SILS plus ERAS program is safe and effective and should be popularised in Crohn’s disease.

Background Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multi-port laparoscopic surgery. Recently, this technique has been applied to Crohn’s disease (CD); however, the application of a laparoscopic approach for complex CD, which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the feasibility and safety of SILS for patients with the complex disease and to compare its clinical results in patients with complex disease. Methods We investigated the feasibility and safety of SILS in sixty patients who underwent SILS for CD were divided into two groups: those with the complex disease (complex group, n = 30), and those with a simple disease (simple group, n = 30). The perioperative data were analysed and compared between the groups. Results The mean operative time and blood loss were 130.5 ± 28.3 min (range 105–166 min) and 230 ± 58 ml (range 116–410 ml) in the complex group, and 113.4 ± 21.5 min (range 95–151 min) and 72 ± 19ml (range 58–115 ml) in the simple group. There were no significant differences in the operative time between the two groups (p = 0.083, >0.05), but the blood loss was significantly greater in the cases of complex group (p = 0.025, 0.05). Conclusion SILS may be feasible and safe for carefully selected patients with complex CD.

The visual quality of photographs can be seriously affected by various low-light conditions. The image enhancement methods based on fusion achieve satisfying results. However, this poses challenges to the situation that there are no fusion sources and only a single low-light image is at hand. In this paper, we propose a single low-light enhancement method by fusing multiple sources, including the original image and its intermediate enhancements generated by a simplified Retinex model. We combine these sources at a mid-level image representation based on a patch-based decomposition model. Compared with other state-of-the-art methods, visual and quantitative results show that our method effectively improves visual effects in terms of lightness, color harmony and vividness.

Background Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor 2 (VEGFR-2) to inhibit tumor angiogenesis, and has shown encouraging anti-tumor effects in multiple solid tumors. Yet clinical evidence of apatinib as a potential treatment choice for RR DLBCL remains rare. In current study, we evaluated the efficacy and safety of Apatinib for patients with RR DLBCL. Methods In this open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two stage design. All patients took Apatinib at an initial dose of 500mg on a 4 weeks cycle at home and visited outpatient clinic every 2 cycles to evaluate the efficacy and to record the adverse events. Dose interruptions and reductions were only allowed when there were grade 3 haematological adverse events or grade 2 non-haematological adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.) Results From January 2017 to February 2019, we screened 35 and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate (DCR) of 71.9%. The median PFS was 6.9 months (95%CI 5.8-7.9) and the median OS was 7.9 months (95%CI 7.0-8.7). Kaplan-Meier estimates of PFS and OS are shown in Figure 1. For patients achieved PR, The median DoR was 5.0 months (95%CI 3.5-6.5). At data analysis time, the median duration of follow-up was 8.6 months (95%CI 7.3-9.4), and 16 (50.0%) patients remained on treatment. 21 patients showed tumor shrinkage comparing with their baseline data and the best percentage changes from baseline are shown in Figure 2. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%) and leukopenia (6.3%). No Apatinib-related deaths were noted. AEs arose in at least one patient are shown in Table 1. Conclusion With the potential superiority of home administration without frequent hospitalization, apatinib can be an arrow in the bow for RR DLBCL patients considering its favorable efficacy, manageable AEs, improved patient adherence and economic effectiveness. Further investigations into this topic will be of profound significance. Disclosures No relevant conflicts of interest to declare.

Background Extranodal NK/T cell lymphoma (ENKTL) is rare in western countries but rather common in Asia and South America, characterized with Epstein-Barr virus (EBV) infection. Patients with advanced stage (III/IV) ENKTL has a poor survival and low response to conventional CHOP-like chemotherapy, with a 5-year overall survival rate of only 30%. Retrospective study showed that SMILE regimen had a certain effect on ENKTL, but the toxicity limited its further clinical application. More effective treatment regimens are required to be explored for systematic, prospective, controlled, randomized clinical trials. Recently, studies revealed that asparaginase-based combination chemotherapy such as P-Gmox(Pegaspargase, Gemcitabine, Oxaliplatin)is effective in patients of ENKTL. However standard treatment for newly untreated advanced ENKTL is still controversial. We developed a refined chemotherapeutic DDGP (dexamethasone, cisplatin, gemcitabline, and peg-asparaginase) regimen and proceeded a prospective randomized, multicenter and open-label clinical trial to evaluate and compare the efficacy and safety of DDGP with SMILE regimen in patients with newly diagnosed stage III/IV ENKTL in January 2011. Based on the encouraging interim results in 2016(Li, L et al.Clin Cancer Res, 2016), we presented the final results of this clinical investigation (ClinicalTrials.gov, No. NCT01501149). Patients and methods: The study was initiated at 9 centers in China in January 2011. Patients aged 14-70 with newly diagnosed ENKTL in stages III/IV, and ECOG performance score of 0-2 were enrolled. According to a computer-generated randomization schedule, eligible patients were assigned either DDGP regimen (cisplatin 20 mg/m² on day 1-4; dexamethasone 15mg/m2 on d1-5; gemcitabine 800mg/m2 on d1,8; pegaspargase 2500 IU/m2 on d1; 21 days per cycle)or SMILE regimen (methotrexate 2g/m2 on d1; dexamethasone 40mg/m2 on d2-4; ifosfamide 1500mg/m2 on d2-4; L-asparaginase 6000 U/m2 on d3-9; etoposide 100 mg/m2 on d2-4; 21 days per cycle) for up to 6 cycles unless disease progression, unacceptable toxicity or patient rejection. Efficacy was evaluated every two cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall response rate (ORR) and overall survival (OS). In addition we compared the safety and tolerability between DDGP and SMILE regimens. The Kaplan-Merier method was used to evaluate for survival of freedom from events, and the log-rank test was used to evaluate differences among two groups. Results: A total of 87 eligible newly diagnosed advanced ENKTL patients were randomly assigned for the study and 80 patients were included into intention-to-treat population (40 patients in DDGP group and 40 patients in SMILE group). Data were collected from January 2011 to February 2019. Baseline characteristics of the two group patients were well balanced. At median follow-up of 41.5 months, the median PFS and OS in the SMILE group were 6.83 months and 75.2 months, respectively, while the median PFS and OS in the DDGP group have not been reached (Fig 1). The 3-year PFS rate and 5-year OS rate in DDGP group were higher than in SMILE group (56.6% vs. 41.8% for 3-year PFS, P=0.004; 74.3% vs. 51.7% for 5-year OS, P=0.02). No difference of the complete remission (CR) rate was observed between two groups, while overall response rate (ORR) in DDGP group was higher than in SMILE group (90.0% vs. 60.0%, p=0.002) (Table 1). More frequently 3/4 grade hematologic toxicities such as leucopenia and netropenia were observed in SMILE group than in DDGP group (p=0.022, p=0.015). Non-hematologic toxicities included elevated transaminase, mucositis and allergy were higher in SMILE group than in DDGP group(p=0.027, p Conclusion: DDGP regimen produced prolonged survival, better tolerability and safety than SMILE regimen in newly diagnosed advanced ENKTL. Disclosures No relevant conflicts of interest to declare.

AIM: The aim of this study was to observe the possible change of microRNAs (miRNAs) in serum extracellular vesicles (EVs) from hepatocellular carcinoma (HCC) patients. METHODS: The serum extracellular vesicles were purified from seventeen healthy donors, sixteen chronic hepatitis B (CHB) patients and twenty-four HCC patients. The sequenced microRNAs in the purified extracellular vesicles were analyzed to obtain highly differentially expressed genes (DEGs). Finally, the expression pattern of DEGs was validated using qRT-PCR. RESULTS: We found that the expression of hsa-miR-21-5p and hsa-miR-144-3p were significantly higher in extracellular vesicles and liver cancer tissues compared with serum and the distal liver tissues in HCC patients. The ratio of hsa-miR-144-3p/hsa-miR-21-5p was significantly decreased in the patients with CHB but significantly increased in patients with HCC developed from CHB (P

Mantle cell lymphoma (MCL) is a rare but deadly subtype of non-Hodgkin's lymphomas because of it can progress rapidly and has a poor prognosis. MicroRNA-199a (miR-199a) is a potential diagnostic marker and therapeutic target for MCL patients. However, the function and molecular mechanisms of miRNA-199a in MCL cells are still unclear. In this study, we first analyzed the levels of miR-199a and C-C chemokine receptor 7 (CCR7) in the tumor tissues and tumor-adjacent tissues, and found that the level of miRNA-199a was lower, whereas the level of CCR7 was higher in tumor tissues. Moreover, overexpression of miR-199a in MCL cells downregulated the level of CCR7. Then, it was found that chemokine (C-C motif) ligand 21 (CCL21), a ligand of CCR7, promoted Granta-519 and Mino cell growth and migration in a concentration-dependent and time-dependent manner. Otherwise, the CCL21/CCR7 pair elevated the level of phosphorylation of protein kinase B and extracellular regulated protein kinases 1/2, upregulated the level of matrix metalloproteinases-2, matrix metalloproteinases-9, and the markers of the mesenchymal phenotype (N-cadherin and vimentin), as well as decreased the level of E-cadherin. However, the functions of CCL21/CCR7 in the growth, migration, and dissemination of MCL cells were decreased by overexpression of miR-199a. Thus, miR-199a inhibited the dissemination of MCL cells by reversing the function of CCL21/CCR7, providing a theoretical basis for miRNA-199a as a potential novel diagnostic marker and therapeutic target for MCL patients.