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Background Ruai-sanyin formula (RASYF) is composed of a variety of anticancer herbs. It is widely used in the treatment of triple negative breast cancer (TNBC) and has proved to inhibit tumor growth and lung metastasis in animal models, but there is no evidence for clinical application in the real world. Methods We conducted this prospective cohort study at 5 research centers in China from November 2016 to December 2018. RASYF was set as an exposure factor. TNBC patients within 3 months after completion of standard adjuvant treatment were included. The exposed group received RASYF treatment, while the non-exposed group received observation. The primary end point was disease-free survival (DFS). Secondary end points included, overall survival (OS), distant disease-free survival (DDFS), relapse-free survival (RFS), QLQ-BR23 assesses quality of life in patients and adverse events. Results A total of 613 eligible patients with operable TNBC were enrolled, of which 588 were included in the Full Protocol Set. At a median follow-up of 48 months, DFS time was longer in those assigned to RASYF compared with observation (3-year DFS, 89.6% vs. 83.5%, [HR = 0.61, 95%CI (0.39-0.95)]; P = 0.03). Similar outcomes were observed for RFS (3-year RFS, 92.1% vs. 85.9%, HR = 0.55, [95% CI, 0.34-0.91]; P = 0.02). However, there was no statistically significant difference in OS and DDFS between the groups. In exploratory subgroup analysis, RASYF benefits were greater in patients with age under the 40 (3-year DFS, 88.4% vs. 76.1%, [HR = 0.45, 95%CI (0.21-0.95)]; P = 0.03). And RASYF is helpful to the improvement of postoperative quality of life. Comparing to the observation group, RASYF increased the mean CFB of BR23 scores in body image (12.34 vs. 8.76, P = 0.03)，sexual function (11.79 vs. 9.23, P P= 0.04), and decreased the scores of systemic therapy side effects (-12.41 vs. -9.24, P = 0.01). Safety analysis showed that RASYF caused major adverse reactions including impaired liver function (4.0%) and stomach pain (6.1%), but the overall security is controllable. Conclusion RASYF supplementation for 2 years after standard adjuvant chemoradiotherapy has certain clinical significance in preventing recurrence and metastasis and improving the quality of life of patients with early TNBC. Trial registration ClinicalTrials.gov: NCT03332368 Registered 6 November, 2017 (retrospectively registered)

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity

Previous SRAM-based computing-in-memory (SRAM-CIM) macros suffer small read margins for high-precision operations, large cell array area overhead, and limited compatibility with many input and weight configurations. This work presents a 1-to-8-bit configurable SRAM CIM unit-macro using: 1) a hybrid structure combining 6T-SRAM based in-memory binary product-sum (PS) operations with digital near-memory-computing multibit PS accumulation to increase read accuracy and reduce area overhead; 2) column-based place-value-grouped weight mapping and a serial-bit input (SBIN) mapping scheme to facilitate reconfiguration and increase array efficiency under various input and weight configurations; 3) a self-reference multilevel reader (SRMLR) to reduce read-out energy and achieve a sensing margin 2 $\times $ that of the mid-point reference scheme; and 4) an input-aware bitline voltage compensation scheme to ensure successful read operations across various input-weight patterns. A 4-Kb configurable 6T-SRAM CIM unit-macro was fabricated using a 55-nm CMOS process with foundry 6T-SRAM cells. The resulting macro achieved access times of 3.5 ns per cycle (pipeline) and energy efficiency of 0.6–40.2 TOPS/W under binary to 8-b input/8-b weight precision.

Computation-in-memory (CIM) is a promising candidate to improve the energy efficiency of multiply-and-accumulate (MAC) operations of artificial intelligence (AI) chips. This work presents an static random access memory (SRAM) CIM unit-macro using: 1) compact-rule compatible twin-8T (T8T) cells for weighted CIM MAC operations to reduce area overhead and vulnerability to process variation; 2) an even–odd dual-channel (EODC) input mapping scheme to extend input bandwidth; 3) a two’s complement weight mapping (C2WM) scheme to enable MAC operations using positive and negative weights within a cell array in order to reduce area overhead and computational latency; and 4) a configurable global–local reference voltage generation (CGLRVG) scheme for kernels of various sizes and bit precision. A 64 $\times $ 60 b T8T unit-macro with 1-, 2-, 4-b inputs, 1-, 2-, 5-b weights, and up to 7-b MAC-value (MACV) outputs was fabricated as a test chip using a foundry 55-nm process. The proposed SRAM-CIM unit-macro achieved access times of 5 ns and energy efficiency of 37.5–45.36 TOPS/W under 5-b MACV output.

Computing-in-memory (CIM) is a promising approach to reduce the latency and improve the energy efficiency of deep neural network (DNN) artificial intelligence (AI) edge processors. However, SRAM-based CIM (SRAM-CIM) faces practical challenges in terms of area overhead, performance, energy efficiency, and yield against variations in data patterns and transistor performance. This paper employed a circuit-system co-design methodology to develop a SRAM-CIM unit-macro for a binary-based fully connected neural network (FCNN) layer of the DNN AI edge processors. The proposed SRAM-CIM unit-macro supports two binarized neural network models: an XNOR neural network (XNORNN) and a modified binary neural network (MBNN). To achieve compact area, fast access time, robust operations, and high energy-efficiency, our proposed SRAM-CIM uses a split-wordline compact-rule 6T SRAM and circuit techniques, including a dynamic input-aware reference generation (DIARG) scheme, an algorithm-dependent asymmetric control (ADAC) scheme, a write disturb-free (WDF) scheme, and a common-mode-insensitive small offset voltage-mode sensing amplifier (CMI-VSA). A fabricated 65-nm 4-Kb SRAM-CIM unit-macro achieved 2.4- and 2.3-ns product-sum access times for a FCNN layer using XNORNN and MBNN, respectively. The measured maximum energy efficiency reached 30.49 TOPS/W for XNORNN and 55.8 TOPS/W for the MBNN modes.

Objective Depressive symptoms and cognitive dysfunction are common in patients with schizophrenia and depressive disorder. This study aimed at exploring whether and how depressive symptoms were correlated with neuro-cognitive impairment in patients with never-treated first-episode (NTFE) schizophrenia. Methods The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to 79 patients and 80 healthy controls to assess neuropsychological function. For all patients, the 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, and the Positive and Negative Syndrome Scale (PANSS) was utilized to assess psychopathological symptoms. Results Thirty-nine patients (49.37%) met the criteria for comorbid depressive symptoms. The RBANS total and the four index scores in the patients were significantly lower than those in the healthy controls. Further, compared with patients without depressive symptoms, patients with depressive symptoms scored lower in attention index, but higher in PANSS general psychopathology and total scores. The HAMD-17 total score was significantly correlated with attention, PANSS total, and PANSS general psychopathology scores. Moreover, multiple regression analysis identified education and HAMD-17 score as the contributors to attention. Conclusion Our results suggest that the rate of depressive symptoms in NTFE schizophrenia is high, which is correlated with neuro-cognitive impairment, especially attention and psychopathology.

This work presents a 1-to-8 bit configurable SRAM CIM unit-macro using (1) a hybrid structure combining 6T-SRAM in-memory binary product-sum (IMBPS) with digital near-memory-computing multi-bit-PS accumulation (DNMPSA) to achieve high read accuracy and compact area, (2) a column-based place-value-grouped weight mapping (CPVGWM) and serial-bit input mapping (SBIN) scheme to facilitate reconfiguration and increase array efficiency for various input/weight precision. A 4Kb configurable 6T-SRAM CIM unit-macro was fabricated using a 55nm CMOS process and foundry 6T cells. The resulting macro achieved 3.5ns access time with 3b PS outputs and gained a 3.91-50x improvement in figure-of-merit, compared to previous SRAM-CIMs.

This work presents a 65nm CMOS speech recognition processor, named Thinker-IM, which employs 16 computing-in-memory (SRAM-CIM) macros for binarized recurrent neural network (RNN) computation. Its major contributions are: 1) A novel digital-CIM mixed architecture that runs an output-weight dual stationary (OWDS) dataflow, reducing 85.7% memory accessing; 2) Multi-bit XNOR SRAM-CIM macros and corresponding CIM-aware weight adaptation that reduces 9.9% energy consumption in average; 3) Predictive early batch-normalization (BN) and binarization units (PBUs) that reduce at most 28.3% computations in RNN. Measured results show the processing speed of 127.3us/Inference and over 90.2% accuracy, while achieving neural energy efficiency of 5.1pJ/Neuron, which is 2.8 × better than state-of-the-art.

Fascin-1, an actin-bundling protein, plays an important role in cancer cell migration and invasion; however, the underlying mechanism remains unclear. On the basis of a 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell migration model, it was shown that TPA increased fascin-1 mRNA and protein expression and fascin-1-dependent cell migration. TPA dose- and time-dependently increased PKCδ and STAT3α activation and GSK3β phosphorylation; up-regulated Wnt-1, β-catenin, and STAT3α expression; and increased the nuclear translocation of β-catenin and STAT3α. Rottlerin, a PKCδ inhibitor, abrogated the increases in STAT3α activation and β-catenin and fascin-1 expression. WP1066, a STAT3 inhibitor, suppressed TPA-induced STAT3α DNA binding activity and β-catenin expression. Knockdown of β-catenin attenuated TPA-induced fascin-1 and STAT3α expression as well as cell migration. In addition to MCF-7, migration of Hs578T breast cancer cells was inhibited by silencing fascin-1, β-catenin, and STAT3α expression as well. TPA also induced Wnt-1 expression and secretion, and blocking Wnt-1 signaling abrogated β-catenin induction. DHA pretreatment attenuated TPA-induced cell migration, PKCδ and STAT3α activation, GSK3β phosphorylation, and Wnt-1, β-catenin, STAT3α, and fascin-1 expression. Our results demonstrated that TPA-induced migration is likely associated with the PKCδ and Wnt-1 pathways, which lead to STAT3α activation, GSK3β inactivation, and β-catenin increase and up-regulation of fascin-1 expression. Moreover, the anti-metastatic potential of DHA is partly attributed to its suppression of TPA-activated PKCδ and Wnt-1 signaling.

Objective This study used a prospective cohort study to observe the effect of triple-negative breast cancer on the 2-year disease-free survival rate with or without “TCM formula”. Methods From November 1 st, 2016, the first patient was enrolled in the cohort study. A total of 356 patients were enrolled on January 30, 2019. Among them, 154 cases were followed up for 2 years. During the follow-up, there were 6 cases of shedding, so 6 cases were affected. A total of 148 cases were included in the analysis, including 73 in the exposed group and 75 in the non-exposed group. The exposed group was given “TCM formula” on the basis of standardized treatment, and the non-exposed group was treated with simple triple-negative breast cancer. The two groups visited each of the three months. The interview included safety examination (hematology and imaging). The endpoint was the difference in 2-year invasive disease-free survival between the exposed and non-exposed groups and the safety of the “TCM formula”. Results There were 6 cases of shedding during the experiment and the shedding rate was 3.9 %. The 2-year rate of invasive disease-free survival in the exposed team was 88.7 % and the non-exposed group was 82.5 %. Logistic multivariate regression analysis predicted that “TCM formula” could reduce the disease-related recurrence and metastasis rate by 11 % (OR = 0.89, 95 % CI 0.37−0.956, P＜0.05). Through K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node stage N1 may be the benefit group of “TCM formula”(P＜0.05). During the study, the incidence of total adverse events was 8.2 % in the exposed group, mainly manifested as stomach discomfort, diarrhea, and hepatocyte damage. Conclusion 1. In the exposed group, the two-year rate of invasive disease-free survival increased by 6.2 % compared with the non-exposed group(P＞0.05). 2. According to K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node metastasis to N1 may be potential beneficiaries of “TCM formula”. 3. “TCM Formula” is safe and tolerable to most patients.

A factorial nitrogen and water addition experiment was carried out with one year-old Machilus pauhoi seedlings from Suichuan County, Jiangxi Province, with six treatments being established: two water levels with 80% and 40% of field moisture holding capacity and three nitrogen addition levels of 0, 50, 100 kg N·hm以种子来源于江西遂川的1年生刨花楠扦插苗为材料,设置田间持水量的80%、40% 2个水分水平,以及不添加(0 kg N·hm

Recent advances in deep neural networks (DNNs) have shown Binary Neural Networks (BNNs) are able to provide a reasonable accuracy on various image datasets with a significant reduction in computation and memory cost. In this paper, we explore two BNNs: hybrid BNN (HBNN) and XNOR-BNN, where the weights are binarized to +1/−1 while the neuron activations are binarized to 1/0 and +1/−1, respectively. Two SRAM bit cell designs are proposed, namely, 6T SRAM for HBNN and customized 8T SRAM for XNOR-BNN. In our design, the high-precision multiply-and-accumulate (MAC) is replaced by bitwise multiplication for HBNN or XNOR for XNOR-BNN plus bit-counting operations. To parallelize the weighted sum operation, we activate multiple word lines in the SRAM array simultaneously and digitize the analog voltage developed along the bit line by a multi-level sense amplifier (MLSA). In order to partition the large matrices in DNNs, we investigate the impact of sensing bit-levels of MLSA on the accuracy degradation for different sub-array sizes and propose using the nonlinear quantization technique to mitigate the accuracy degradation. With 64 × 64 sub-array size and 3-bit MLSA, HBNN and XNOR-BNN architectures can minimize the accuracy degradation to 2.37% and 0.88%, respectively, for an inspired VGG-16 network on the CIFAR-10 dataset. Design space exploration of SRAM based synaptic architectures with the conventional row-by-row access scheme and our proposed parallel access scheme are also performed, showing significant benefits in the area, latency and energy-efficiency. Finally, we have successfully taped-out and validated the proposed HBNN and XNOR-BNN designs in TSMC 65 nm process with measured silicon data, achieving energy-efficiency >100 TOPS/W for HBNN and >50 TOPS/W for XNOR-BNN.

Background: Breast cancer (BC) poses a tremendous threat to the health of women worldwide, especially triple-negative breast cancers (TNBCs). Currently, the curative effect of traditional Chinese medicine (TCM) has been recognized in more and more people worldwide; however, the specific effect has not been systematically evaluated. The purpose of this cohort study is to evaluate the clinical effects of TCM syndrome differentiation on recurrence and metastasis rate, survival rate, and the quality of life in patients with TNBC. Methods: This study is a multicenter observational cohort trial taking 2 years. A total of 620 patients will be allocated at a ratio of 1:1 to receive TCM or not. The primary outcomes are progression-free survival (PFS) and overall survival (OS), which are calculated at the end of the trial. Secondary outcomes include TCM symptoms, Karnofsky Performance Status (KPS), ECOG score, European Organization for Research and Treatment of Cancer (EORTC) Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23), as well as clinical indicators including tumor markers, immune function evaluation, chest computed tomography/magnetic resonance imaging, and abdominal B-ultrasound. Assessments will be performed at baseline and 3, 6, 9, 12, 16, and 20 weeks after observation. Discussion: This will be the first clinical trial to evaluate the PFS and OS in TNBC patients receiving TCM, which may be used to assess the feasibility of a larger-scale clinical trial in the future, and formulate a standardized TCM treatment plan. Study registration: ClinicalTrials.gov (NCT03332368).

Alumina was modified by doping with metal oxide and then used as the support for depositing gold by an impregnation-ammonia washing method to obtain Au/MxOy/Al2O3(M=Co, Zr and Ce) catalysts. These samples were characterized by inductively coupled plasma-atomic emission spectrometry (ICP-AES), transmission electron microscope (TEM) and X-ray diffraction (XRD). The effects of Co3O4content, metal oxide and mixed metal oxides on the catalytic activity for the selective oxidation of cyclohexane to cyclohexanone and cyclohexanol using molecular oxygen as oxidant were studied. The results showed that better catalytic performance was obtained over Au/MxOy/Al2O3catalysts compared with over Au/Al2O3catalysts. 9.69% conversion of cyclohexane and 93.31% selectivity to cyclohexanone, cyclohexanol and cyclohexyl hydroperoxide, with 1.02 ratio of cyclohexanone to cyclohexanol were obtained over the Au/MxOy/Al2O3catalyst at 150 , 1.5 MPa for 3 h. Moreover, according to the recycling test, the catalyst could be reused four times without remarkable loss of activity.

We have noticed a misplaced figure in our paper “Antimetastatic Potentials of Dioscorea nipponica on Melanoma In Vitro and In Vivo” [1]. There is an error that occurred during uploading Figure 4(e). The published microscopy image of cell invasion for treatment of Dioscorea nipponica ethyl acetate extracts (DNE3) on B16F10 cells is incorrect. We have attached a correct version (Figure 4(e)). Figure 4

Recent studies have revealed pleiotropic anticancer and antiproliferative capabilities ofDioscorea nipponicaMakino whereas the effect of this plant on metastasis of cancer cells has not been clearly clarified. In the present study, we extractedDioscorea nipponicaMakino with methanol (DNE1), chloroform (DNE2), ethyl acetate (DNE3),n-butanol (DNE4), and water (DNE5). We first demonstrate that DNE3 was found to be effective in reducing the lung metastases formation by about 99.5% as compared to vehicle-treated control animals. When a nontoxic concentration of the extract was treated directly to highly metastatic murin melanoma cells (B16F10) and human melanoma cells (A2058)in vitro, it exerted a dose-dependent inhibitory effect on the invasion(P<.001), motility(P<.001), secretion of MMPs(P<.001), and u-PA(P<.001)of both cell lines. To investigate the possible mechanisms involved in these events, we performed western blot analysis to find that DNE inhibited phosphorylation of Akt. A treatment with DNE3 to B16F10 cells also inhibited the activation of NF-κB and increased the expression of IkappaB. Taken together, these findings suggested that DNE3 could reduce the metastasis of melanoma cells, thereby constituting an adjuvant treatment for metastasis control.

To observe the treatments on the patients with acute methamidophos dichlorvos (DDV) and omethoate poisoning and provide the reliable basis for the rational treatments on these three organophosphorus pesticides poisoning.101 patients with AOPP in 7 hospitals were divided into three groups: Group A, 59 patients with acute methamidophos poisoning, Group B, 32 patients with acute DDV/dipterex (DEP) poisoning, Group C, 10 patients with acute omethoate/dimethoate poisoning. The levels of erythrocyte AChE and the therapeutic efficacies of pralidoxime chloride (PAM-Cl) were compared among the three groups.The AChE activities of all the three groups were inhibited on level of (9.12 +/- 7.99) U/g Hb (group A), 7.32 +/- 4.62 U/g Hb (group B) and (12.01 +/- 9.53) U/g Hb (group C), among which no significant difference was found (P0.05). All the patients recovered from acute cholinergic excitation or crisis after the treatment of PAM-Cl. The erythrocyte AChE activities were obviously reactivated in group A three hours later after admission to hospital, each on level of (11.37 +/- 8.67) U/g Hb, (12.51 +/- 6.98) U/g Hb, (15.90 +/- 7.31) U/g Hb, (18.33 +/- 4.78) U/g Hb and (18.91 +/- 7.00) U/g Hb at the 12th, 24th, 48th, 72nd hour and discharge (P0.05), and the upgrade tendency was continuous. AChE activities in group B were also reactivated after treatment, each on level of (8.91 +/- 5.89) U/g Hb, (1.31 +/- 6.61) U/g Hb, (13.00 +/- 7.55) U/g Hb, (14.22 +/- 7.80) U/g Hb, (12.78 +/- 7.07) U/g Hb and (16.87 +/- 7.06) U/g Hb at the 3rd, 12th, 24th, 48th, 72nd hour and discharge, but the upgrade tendency turned slowly after 12 hours, the inhibited AChE activities were not reactivated in group C from the beginning to the end.After the treatment of PAM-Cl, the AChE activities of the patients with acute methamidophos poisoning could be continuously reactivated, the AChE activities of the patients with acute DDV/DEP poisoning could also be reactivated in 12 hours, and then keep stable, but the AChE activities of the patients with acute omethoate/dimethoate poisoning could not be reactivated. However, PAM-Cl has therapeutic efficacy against acute toxicity of all the three organophosphorus pesticides. Oximes should be vigorously used in the treatment of AOPP, including acute omethoate/dimethoate poisoning.

Running conditions of pulverized coal pipes and mills are of greatly effecting on the combustion and safely operation of utilities in coal-fired power plants. However, there are less effective ways to on-line measure or diagnose the pipes or mills. Based on light fluctuation method, the on-line measurement of size and concentration of pulverized coal were presented in this work. Moreover, the velocity of pulverized coal in pipes was measured by cross correlation method. A novel on-line monitoring system was designed with above measurement principles. The on-line monitoring system was applied to measure pulverized coal pipes and mills in-situ in a 1000MW ultra supercritical unit. The unit had 48 pulverized coal pipes and adopted three-layer opposed firing pattern. The experimental results showed the on-line monitoring system can simultaneously measure the size, concentration and velocity of pulverized coal in different coal pipes accurately and quickly. Using these parameters, the running condition of pulverized coal pipes and mills can be diagnosed. Therefore, this work provided a practical method and instrument for on-line monitoring technology of pulverized coal pipes and mills.