A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival.

Background: Both CellSearch and CellCollector have been accepted as the proper devices to capture CTC by domestic approval department. However, there is little article about the comparison between these two devices around the world. Herein, we conducted the real-world study to compare with these two devices and to re-verify the efficacy of CTC counts. Methods: Patients who meet the following points should be included in the analysis. 1. Female, aged 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) score 0-2; 3. With at least one measurable tumor lesion; 4. Clear immunohistochemistry result; 5. Accept at least one CTC test. Patients were excluded in the analysis if they had a history of malignant tumors, incomplete follow-up information. Results: 536 metastatic breast cancer patients who had been detected for CTC at least once by CellSearch or CellCollector were included in the analysis. CellCollector in vivo CTC detection technology has a higher detection rate than the CellSearch system (69.2% vs 57.4%, P = 0.009). However, the proportion of CTC≥5 detected by CellSearch was higher than CellCollector (37.4% vs 16.3%, P < 0.001). There was a statistically significant difference in overall survival of patients with CTC negative and CTC positive (mOS:49.8 months vs 26.9 months). After 4 weeks of treatment, when CTC decreased by more than 50%, there was a significant difference in survival between the two groups (40.1 months vs 25.8 months, HR = 0.588, 95% CI: 0.350-0.933). In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269-0.887). Conclusions: Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients.

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.

Enhanced Contact Performance and Thermal Tolerance of Ni/Bi2Te3 Joints for Bi2Te3-Based Thermoelectric Devices.

Ni metal has been widely used as a barrier layer in Bi2Te3-based thermoelectric devices, which establishes stable joints to link Bi2Te3-based legs and electrodes. However, the Ni/Bi2Te3 joints become very fragile when the devices were exposed to high temperature, causing severe performance deterioration and even device failure. Herein, stable Ni/Bi2Te3 joints have been established by arc spraying of the Ni barrier layer on the Bi2Te3-based alloys. The interface microstructure and contact performance including the bonding strength and contact resistivity of the arc-sprayed Ni/Bi2Te3 joints are investigated. The results indicate that, as compared with traditional Ni/Bi2Te3 joints, the arc-sprayed Ni/Bi2Te3 joints have comparably low contact resistivity while possessing a 50% higher bonding strength. Aging the joints as an exposure to high-temperature circumstances, the arc-sprayed Ni/Bi2Te3 joints exhibit much better tolerance to the thermal shock with stable bonding strength and contact resistivity. The enhanced interfacial contact performance and thermal tolerance should be attributed to the thick Ni barrier layer and interface reaction layer with good Ohmic contact. This work provides an effective strategy to establish stable joints for the Bi2Te3-based thermoelectric devices with improved thermal stability.

Novel Anti-HER2 Antibody-Drug Conjugates Versus T-DM1 for HER2-Positive Metastatic Breast Cancer After Tyrosine Kinase Inhibitors Treatment.

BACKGROUND: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. MATERIALS AND METHODS: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. CONCLUSIONS: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

The expression of agmatinase manipulates the affective state of rats subjected to chronic restraint stress.

Agmatine is an endogenous polyamine produced from l-arginine and degraded by agmatinase (AGMAT). Studies in humans and animals have shown that agmatine has neuroprotective, anxiolytic, and antidepressant-like actions. However, little is known about the role of AGMAT in the action of agmatine or in the pathophysiology of psychiatric disorders. Therefore, this study aimed to investigate the role of AGMAT in the pathophysiology of MDD. In this study, we observed that AGMAT expression increased in the ventral hippocampus rather than in the medial prefrontal cortex in the chronic restraint stress (CRS) animal model of depression. Furthermore, we found that AGMAT overexpression in the ventral hippocampus elicited depressive- and anxiety-like behaviors, whereas knockdown of AGMAT exhibited antidepressant and anxiolytic effects in CRS animals. Field and whole-cell recordings of hippocampal CA1 revealed that AGMAT blockage increased Schaffer collateral-CA1 excitatory synaptic transmission, which was expressed both pre- and post-synaptically and was probably due to the inhibition of AGMAT-expressing local interneurons. Therefore, our results suggest that dysregulation of AGMAT is involved in the pathophysiology of depression and is a potential target for designing more effective antidepressants with fewer adverse effects to offer a better therapy for depression.

Efficacy and safety of pyrotinib and radiotherapy vs. pyrotinib-based therapy in patients with HER2+ breast cancer with brain metastasis: a retrospective cohort study.

Background: At present, local therapy, such as surgery and radiotherapy, is the mainstay treatment for brain metastasis and anti-human epidermal growth factor receptor type 2 (HER2)-targeted therapy has been shown to be efficacious for HER2+ breast cancer (BC) patients with brain metastasis. However, Clinical studies comparing the combined effects of the two treatments are lacking. This study sought to investigate the efficacy and safety of pyrotinib and radiotherapy versus pyrotinib-based therapy in treating HER2+ BC patients with brain metastasis. Methods: This retrospective, observational study collected data from 79 HER2+ BC patients with brain metastasis who received pyrotinib-based therapy from May 2018 to December 2021. Among these patients, 35 received pyrotinib-based therapy concurrently with, or within 3 months before or after, brain radiotherapy (Group A), and 44 received pyrotinib-based therapy as the primary regimen (with no restriction as to whether they had received brain radiotherapy previously or not, the interval between receiving radiotherapy and receiving pyrotinib was >3 months) (Group B). Patient information was collected by the Electronic Medical Records System. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the objective response rate (ORR), the clinical benefit rate (CBR), and safety. The assessment of adverse effects was based on CTCAE5.0. Results: The intracranial ORRs were 48.6% in Group A and 20.5% (9/44) in Group B (P=0.015). The intracranial CBRs were 80.0% in Group A and 65.9% in Group B. The median intracranial PFS times (IC-PFS) were 15.0 months and 9.0 months in Group A and Group B, respectively (P=0.385). There was no statistically significant difference in OS between the 2 groups (95.0 vs. 98.0 months, P=0.872). The subgroup analysis showed that patients with active brain metastasis who received pyrotinib and radiotherapy had a longer IC-PFS time than those who received pyrotinib-based therapy(P=0.056). No serious adverse reactions (e.g., acute brain edema, cognitive dysfunction, or treatment-related death events) were observed. Conclusions: Pyrotinib combined with radiotherapy is recommended for HER2+ breast cancer active brain metastasis patients who can tolerate radiotherapy and pyrotinib. Pyrotinib-based therapy may be considered for patients who cannot tolerate radiotherapy and pyrotinib.

[Correlation analysis of lipid level and cognitive function in middle-aged and elderly diabetic population from 2 communities in Beijing in 2017].

OBJECTIVE: To investigate the relationship between serum lipid level and cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus(T2 DM). METHODS: A cross-sectional study was implemented in 2017 to explore the correlation between lipid level and cognitive function in middle-aged and elderly diabetic patients. A random sample of 1526 middle-aged and elderly people were recruited from 2 communities in Beijing. Fasting blood samples were collected for blood lipid level detection, and the cognitive function of the subjects was assessed by the Montreal Cognitive Assessment Scale(MoCA). Logistic regression model was used to analyze the correlation between serum lipid levels and mild cognitive impairment(MCI) in elderly and T2 DM patients and control group. RESULTS: Compared with the control group, there were significant differences in blood lipid levels in T2 DM group. The levels of total cholesterol(TC) and high density lipoprotein cholesterol(HDL-C) in T2 DM group were lower than those in the control group, while triglyceride(TG) and low density lipoprotein cholesterol(LDL-C) were higher than those in the control group. Logistic regression analysis showed that high level of TC was a risk factor for MCI in patients with T2 DM, while high level of LDL-C was a protective factor, but no association was observed in the control population. CONCLUSION: Phenotype of T2 DM may affect the relationship between lipid level and cognitive function in middle-aged and elderly people.

Clinical outcomes of tucidinostat-based therapy after prior CDK4/6 inhibitor progression in hormone receptor-positive heavily pretreated metastatic breast cancer.

BACKGROUND: CDK4/6 inhibitors combined with endocrine therapy are standard first- or second-line treatment for patients with HR-positive and HER2-negative advanced breast cancer, however, there is currently no optimal recommendation for therapeutic strategies after progression on CDK4/6i. The aim of this study is to analyze the efficacy and safety of HDAC inhibitor Tucidinostat combined with endocrine therapy in patients after prior CDK4/6 inhibitor progression. METHODS: The pathological and clinical data of 44 HR-positive and HER2-negative breast cancer patients treated with tucidinostat after progression on CDK4/6i at the Breast Oncology Department of the Fifth Medical Center of the PLA General Hospital from July 2019 to October 2021 were retrospectively analyzed. Observation indexes included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR) and adverse events. At the same time, we attempted to identify potential genomic predictors using available next-generation sequencing (NGS). RESULTS: A total of 44 patients were enrolled in this study. Median follow-up was 10 months (1-26 months) by the data cutoff date (February 2022). The CBR was 6.8% (3/44), the median PFS was 2.0 months (95% CI 1.9-2.1), and the median OS was 14 months (95% CI 6.3-21.7). The mPFS was 4.1 months (95%CI: 0-8.2) in patients with 1 metastatic site, and the mPFS was 4.5 months (95%CI: 4.2-4.8) in patients who received sequential tucidinostat after CDK4/6i failure. Multivariate analysis showed that patients with 1 metastatic site or sequential tucidinostat treatment after failure of CDK4/6i were more likely to benefit from tucidinostat combined with endocrine therapy. Preliminary data showed PIK3CA mutation may be associated with resistance of tucidinostat therapy. No grade 4 adverse events and no treatment-related deaths were recorded in the study. Dose reductions because of adverse events occurred in 4 (9.1%) patients. CONCLUSIONS: This study preliminarily shows that tucidinostat combined with endocrine therapy may be an optional sequential strategy for patients with HR+/HER2-advanced breast cancer that has progressed on CDK4/6 inhibitor, especially for these with lower tumor burden and fewer prior palliative treatment.

An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer.

Background: Neoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain. Methods: The study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and TUMORFISH) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy. Results: The sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods. Conclusions: Our study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

BACKGROUND: To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data. METHODS: Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated. RESULTS: A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy. The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed. CONCLUSIONS: Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

A Multipulse Radar Signal Recognition Approach via HRF-Net Deep Learning Models.

In the field of electronic countermeasure, the recognition of radar signals is extremely important. This paper uses GNU Radio and Universal Software Radio Peripherals to generate 10 classes of close-to-real multipulse radar signals, namely, Barker, Chaotic, EQFM, Frank, FSK, LFM, LOFM, OFDM, P1, and P2. In order to obtain the time-frequency image (TFI) of the multipulse radar signal, the signal is Choi-Williams distribution (CWD) transformed. Aiming at the features of the multipulse radar signal TFI, we designed a distinguishing feature fusion extraction module (DFFE) and proposed a new HRF-Net deep learning model based on this module. The model has relatively few parameters and calculations. The experiments were carried out at the signal-to-noise ratio (SNR) of -14 ∼ 4 dB. In the case of -6 dB, the recognition result of HRF-Net reached 99.583% and the recognition result of the network still reached 97.500% under -14 dB. Compared with other methods, HRF-Nets have relatively better generalization and robustness.

A Radar Signal Recognition Approach via IIF-Net Deep Learning Models.

In the increasingly complex electromagnetic environment of modern battlefields, how to quickly and accurately identify radar signals is a hotspot in the field of electronic countermeasures. In this paper, USRP N210, USRP-LW N210, and other general software radio peripherals are used to simulate the transmitting and receiving process of radar signals, and a total of 8 radar signals, namely, Barker, Frank, chaotic, P1, P2, P3, P4, and OFDM, are produced. The signal obtains time-frequency images (TFIs) through the Choi-Williams distribution function (CWD). According to the characteristics of the radar signal TFI, a global feature balance extraction module (GFBE) is designed. Then, a new IIF-Net convolutional neural network with fewer network parameters and less computation cost has been proposed. The signal-to-noise ratio (SNR) range is -10 to 6 dB in the experiments. The experiments show that when the SNR is higher than -2 dB, the signal recognition rate of IIF-Net is as high as 99.74%, and the signal recognition accuracy is still 92.36% when the SNR is -10 dB. Compared with other methods, IIF-Net has higher recognition rate and better robustness under low SNR.

Platform-independent approach for cancer detection from gene expression profiles of peripheral blood cells.

Peripheral blood gene expression intensity-based methods for distinguishing healthy individuals from cancer patients are limited by sensitivity to batch effects and data normalization and variability between expression profiling assays. To improve the robustness and precision of blood gene expression-based tumour detection, it is necessary to perform molecular diagnostic tests using a more stable approach. Taking breast cancer as an example, we propose a machine learning-based framework that distinguishes breast cancer patients from healthy subjects by pairwise rank transformation of gene expression intensity in each sample. We showed the diagnostic potential of the method by performing RNA-seq for 37 peripheral blood samples from breast cancer patients and by collecting RNA-seq data from healthy donors in Genotype-Tissue Expression project and microarray mRNA expression datasets in Gene Expression Omnibus. The framework was insensitive to experimental batch effects and data normalization, and it can be simultaneously applied to new sample prediction.

JS001, an anti-PD-1 mAb for advanced triple negative breast cancer patients after multi-line systemic therapy in a phase I trial.

BACKGROUND: Triple negative breast cancer (TNBC), as defined by ER, PR and HER2 negative expression in tumor, has limited treatment options beyond conventional chemotherapy. JS001, a humanized IgG4 antibody for PD-1, has demonstrated acceptable safety profile and preliminary anti-tumor activity in solid tumors. METHODS: This phase I open-label study is designed to evaluate the safety, tolerability, and antitumor activity of JS001 in advanced TNBC patients who are refractory to standard systemic therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg Q2W followed by a dose expansion cohort at 3 mg/kg. (Clinical Trial ID: NCT02838823). RESULTS: From August 04, 2016 to October 26, 2017, 20 heavily-pretreated advanced TNBC patients were enrolled into three dose cohorts (6 in 1 mg/kg, 8 in 3 mg/kg and 6 in 10 mg/kg). As of August 30, 2018, no DLT was observed and no MTD was reached. No AEs were grade 4 or 5. The most common treatment related AEs were all grade 1/2. Treatment related grade 3 AEs (15%) included 1 hyponatremia, 1 rash and 1 bronchospasm (infusion related reaction). Among 20 evaluable subjects, the ORR was 5%. One patient in 10 mg/kg group obtained PR, who was PD-L1 strong positive (>50%) in tumor biopsy, with treatment duration of 12.8 months as of data cutoff. As of follow-up on July 15, 2019, the patient continued PR with treatment duration of 24 months and still ongoing. Six patients achieved SD, for a DCR of 35%. The median PFS of all subjects was 1.8 months (95% CI, 1.4 to 4.6). 45% subjects are PD-L1 positive (≥1% cutoff), among whom a 11.1% ORR and a 22.2% DCR were observed. CONCLUSIONS: JS001 exhibited a favorable safety profile in advanced TNBC patients who are refractory to multi-line systemic therapy. JS001 also showed a moderate response in these TNBC patients who had limited treatment options.

Gas-Phase Photoelectrocatalysis for Breaking Down Nitric Oxide.

Photoelectrocatalysis (PEC) produces high-efficiency electron-hole separation by applying a bias voltage between semiconductor-based electrodes to achieve high photocatalytic reaction rates. However, using PEC to treat polluted gas in a gas-phase reaction is difficult because of the lack of a conductive medium. Herein, we report an efficient PEC system to oxidize NO gas by using parallel photoactive composites (TiO2 nanoribbons-carbon nanotubes) coated on stainless-steel mesh as photoanodes in a gas-phase chamber and Pt foil as the working electrode in a liquid-phase auxiliary cell. Carbon nanotubes (CNTs) were utilized as conductive scaffolds to enhance the interaction between TiO2 and stainless-steel skeletons for accelerated photogenerated electron transfer. Such a PEC system exhibited super-high performance for the treatment of indoor NO gas (550 ppb) with high selectivity for nitrate under UV-light irradiation owing to the conductive, intertwined network structure of the photoanode, fast photocarrier separation, and longer photogenerated hole lifetime. The photogenerated holes were proven to be the most important active sites for directly driving PEC oxidation of indoor NO gas, even in the absence of water vapor. This work created an efficient PEC air-purification filter for treating indoor polluted air under ambient conditions.

DHA and vitamin E antagonized the Aß25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells.

The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 µmol L-1 Aß25-35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets' gene and protein expression. Our results indicated that the Aß25-35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aß25-35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aß25-35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aß25-35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.

Diminished circulating retinol and elevated α-TOH/retinol ratio predict an increased risk of cognitive decline in aging Chinese adults, especially in subjects with ApoE2 or ApoE4 genotype.

OBJECTIVE: The current study evaluated the relationship between circulating fat soluble vitamin status and cognition in aging Chinese population. METHODS: A cross-sectional study was carried out in 1754 community residents aged 55-80 years aiming to evaluate the relationship between circulating α-tocopherol and retinol status and cognition. The effect of ApoE genetic polymorphism on the relationship between vitamins and cognition was also explored. RESULTS: Our results indicated that serum retinol status positively correlated with cognitive performance; while, serum α-tocopherol (α-TOH)/retinol ratio negatively correlated with cognitive performance. Mild cognitive impairment (MCI) subject demonstrated higher serum α-TOH status (P < 0.05), α-TOH/retinol ratio (P < 0.01) and lower retinol status (P < 0.01) than normal subjects. Subjects with ApoE4 genotype have lower serum retinol level (P < 0.05) and higher α-TOH/retinol ratio (P < 0.01) than subjects with ApoE3 genotype. MCI-ApoE4 carriers demonstrated the worst cognitive performance (P < 0.05) and exhibited higher serum TC, α-TOH and α-TOH/retinol ratio levels (P < 0.05), and lower LDL-C, retinol and lipid-adjusted retinol status (P < 0.05). MCI-ApoE2 subjects showed higher serum TC, HDL-C content and α-TOH/retinol ratio (P < 0.05); and lower serum retinol and lipid-adjusted retinol status (P < 0.05). CONCLUSION: Lower circulating retinol and higher α-TOH/retinol ratio potentially predicts an increased risk for the development of cognitive decline in aging Chinese adults. ApoE2 or E4 carriers with higher circulating α-TOH/retinol ratio infer poor cognitive performance and an increased risk of developing MCI.

Association of ApoE Genetic Polymorphism and Type 2 Diabetes with Cognition in Non-Demented Aging Chinese Adults: A Community Based Cross-Sectional Study.

Apolipoprotein E (ApoE) gene polymorphism has been implicated in predisposition to diabetes and dementia in old population, but the results from the different studies were inconclusive. A cross-sectional study was carried out to explore the relationship among ApoE gene polymorphism, diabetes and cognition in non-demented aging Chinese adults. A total number of 1000 community dwellers aged 55 years and above were randomly recruited. Demographic information of the participants was collected using well designed self-administered questionnaires. The Montreal Cognitive Assessment (MoCA) test was employed to evaluate the cognitive status of the participants. Semi-quantitative food frequency questionnaire was used to obtain the dietary intake information. Fasting venous blood samples were taken for ApoE genotyping and serum lipid measurements. 238 participants were type 2 diabetes mellitus (T2DM) patients and 145 participants were ApoE4 carriers. ApoE 4-T2DM subjects had higher serum triglyceride (TG) concentration than E2 and E3 carriers (P < 0.05). T2DM subjects carrying ApoE4 had lower cognition than subjects with E2 or E3 carriers (P < 0.05). Comparing to non-type 2 diabetic mild cognitive impaired (nT2DM-MCI) subjects, the type 2 diabetic mild cognitive impaired (T2DM-MCI) subjects have higher serum glucose (Glu) level and lower high-density lipoprotein (HDL-C) level (P < 0.05). The T2DM-MCI subjects carrying ApoE4 have lower cognition than E2 and E3 carriers (P <0.05); and the interaction of ApoE genotype with T2DM was detected (P < 0.05). Our results indicated the association among ApoE gene polymorphism, T2DM and cognitive performance in non-demented aging population. The carrying of ApoE4 predisposed the T2DM subjects and the T2DM-MCI subjects to have poor cognitive performance. Additional experimental studies are required to explore the mechanism that ApoE genotype modifies the risk for cognitive impairment in aging subjects with T2DM.

The Role of ApoE Polymorphism in the Relationship between Serum Steroid Hormone Levels and Cognition in Older Chinese Adults: A Cross-Sectional Study.

BACKGROUND: Epidemiology studies have indicated an association of apolipoprotein E (ApoE) genetic polymorphism and circulating steroid hormone levels with the risk of Alzheimer's disease. The established physiologic relationship between apolipoproteins and steroid hormone indicate an important role of ApoE polymorphism in impacting the relationship between serum steroid hormones and cognition in the elderly. STUDY DESIGN: A total of 500 Chinese adults aged between 50 and 75 participated in this community-based cross-sectional study. Blood samples were collected in the morning for ApoE genotyping and serum parameter assessment. Cognitive performance of participants was evaluated by Montreal Cognitive Assessment test. RESULTS: Age, gender, educational level, smoking, and physical activity levels are factors associated with cognitive performance in this older Chinese adults. Compared to the control subjects, MCI subjects demonstrated higher serum total cholesterol, HDL-C, and estradiol status (P < 0.05). ApoE genotype difference of serum lipid profile was observed with a relatively higher mean serum triglyceride levels in ApoE2 and ApoE4 carriers (P < 0.05), and lower mean serum HDL-C level in ApoE4 carriers (P < 0.05). Memory and delayed recall ability was serum estradiol level related; and subjects with higher circulating estradiol concentration exhibited lower memory and delayed recall ability (P < 0.05). The association of serum estradiol and cortisol concentration with cognitive performance was ApoE genotypes dependent. Poor cognitive performance was observed in ApoE2 and ApoE4 carriers with higher serum estradiol level (P < 0.05). Moreover, ApoE2 and ApoE4 carriers with higher serum cortisol status demonstrated decreased language ability (P < 0.05). Multiple logistic regression analysis indicates that subjects with higher serum estradiol status may have an increased risk for MCI [OR = 2.004, 95% confidence interval (CI): 1.135, 3.540; P = 0.017]. ApoE2 carriers with higher serum steroid levels may be potentially predisposed to an increased risk of MCI (OR = 3.353; 95% CI: 1.135, 9.907; P = 0.029). CONCLUSION: Cognitive outcomes in older Chinese adults are associated with serum steroid hormone status. Higher serum steroid levels in ApoE2 carriers might pose an increased risk of MCI in the elderly.

Determinants of multidrug-resistant tuberculosis in Henan province in China: a case control study.

BACKGROUND: Multi-drug resistance (MDR) has been a cause of concern for tuberculosis (TB) control in both developed and developing countries. This study described the characteristics and risk factors associated with MDR-TB among 287 cases and 291 controls in Henan province, China. METHODS: A hospital-based case-control study was conducted between June 2012 and December 2013. The study subjects were selected using multistage probability sampling. Multivariate conditional logistic regression models were used to determine the risk factors associated with MDR-TB. RESULTS: The following risk factors for MDR-TB were identified: previous TB treatment (AOR = 4.51, 95% CI: 3.55-5.56), male sex (AOR = 1.09, 95% CI: 0.24-1.88), high school or lower education degree (AOR = 1.87, 95% CI: 1.27-2.69), unemployment (AOR = 1.30, 95% CI: 0.78-2.52), long distance of residence from the health facility (AOR = 6.66,95% CI: 5.92-7.72), smoking (AOR = 2.07, 95% CI: 1.66-3.19), poor knowledge regarding MDR-TB (AOR = 2.06, 95% CI: 1.66-2.92), traveling by foot to reach the health facility (AOR = 1.85, 95% CI: 1.12-3.09), estimated amount of time to reach the health facility was greater than 3 h (AOR = 1.42, 95% CI: 0.51-2.35), social stigma (AOR = 1.17, 95% CI: 0.27-2.03), having an opportunistic infection (AOR = 1.45, 95% CI: 0.58-2.4), more than 3 TB foci in the lungs (AOR = 1.98, 95% CI: 1.49-3.25), total time of first treatment was more than 8 months (AOR = 1.39, 95% CI: 0.65-2.54), adverse effects of anti-TB medication (AOR = 2.39, 95% CI: 1.40-3.26), and more than 3 prior episodes of anti-TB treatment (AOR = 1.83, 95% CI: 1.26-2.80). CONCLUSION: The identified risk factors should be given priority in TB control programs. Additionally, there is a compelling need for better management and control of MDR-TB, particularly through increasing laboratory capacity, regular screening, enhancing drug sensitivity testing, novel MDR-TB drug regimens, and adherence to medication.