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Whether peripheral immune cell subsets can predict pathological complete response (pCR) in breast cancer patients remains to be elucidated. We aimed to dissect the relationship between peripheral immune cell subsets and pCR.Two hundred and twenty-six eligible patients from two prospective clinical trials (SHPD001 and SHPD002) in China were randomly divided into a training cohort and a validation cohort. The breast cancer subtypes in this study included hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 95), HER2-positive (n = 100), and triple negative (n = 31) breast cancer. We defined the "Neo-Peripheral Adaptive Immune Score" for neoadjuvant chemotherapy (neoPAI Score) based on the percentages of CD4 + T cells, CD8 + T cells, B cells, and the CD4 + /CD8 + ratio in peripheral blood. We also evaluated the ability of the neoPAI Score derived from tumor-infiltrating immune cells (TIICs) to predict survival by employing The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database.In the training cohort, multivariate analysis showed that HR status [odds ratio (OR) 0.325; 95% confidence interval (CI) 0.135-0.761; P = 0.010], HER2 status (OR 2.657; 95% CI 1.266-5.730; P = 0.011), Ki67 index (OR 3.191; 95% CI 1.509-6.956; P = 0.003), histological grade (OR 2.297; 95% CI 1.031-5.290; P = 0.045) and neoPAI Score (OR 4.451; 95% CI 1.608-13.068; P = 0.005) were independent predictors of pCR. In the validation cohort, histological grade (OR 3.779; 95% CI 3.793-1.136 × 10The neoPAI Score defined by the percentages of peripheral immune cell subsets could be used as a potential biomarker for neoadjuvant chemotherapy efficacy.

The intensity of static electric field (SEF) in the surrounding environment of transmission lines has been greatly increased with the rapid development of ultra-high-voltage direct-current transmission. Therefore, the potential health effects of SEF have stimulated great public attention. It has been proven that SEF exposure can cause reversible damage to the nervous system through oxidative stress; however, the mechanism of its recovery is unclear. This study focused on nuclear factor erythroid 2-related factor 2 (Nrf2), a vital regulator of oxidative stress, and has been identified to notably impact the protection of organisms against many external stimuli. Herein, it was found that 56.3 kV/m SEF exposure for 7 days and 14 days significantly improved the expression levels of Nrf2 protein in the cytoplasm and nucleus of mice' hippocampus, as well as antioxidant genes, superoxide dismutase 2, and glutathione peroxidase 1. No significant difference in the expression level of the Nrf2 gene was found. The results indicated that the body could activate the Nrf2 signalling under SEF exposure by means other than up-regulation of Nrf2 gene expression. Inhibiting Nrf2 signalling by isoniazid could block SEF-induced gene transcription and protein expression, resulting in a decrease in antioxidant capacity, an increase in the level of lipid peroxide product, and irretrievability of learning and memory damage. These results demonstrated that the Nrf2 signalling pathway exhibited a protective role in SEF-induced oxidative damage and decline in learning and memory ability, which provides a potential strategy for preventing and treating SEF-related neurotoxicity.

BACKGROUND: Qinxiang Qingjie (QXQJ), an oral solution containing various Chinese herbs, is indicated for pediatric upper respiratory tract infections. The treatment of influenza also shows potential advantages in shortening the duration of illness and improving symptoms. However, there is still a lack of high-quality clinical evidence to support this. The trial was to explore the efficacy and safety of QXQJ for treating pediatric influenza and provide an evidence-based basis for expanding its applicability. METHODS: A randomized, double-blind, double-dummy, positive-controlled, multicenter clinical trial was conducted in 14 hospitals in China. Children aged 1–13 years with influenza and “exterior and interior heat syndromes” as defined by traditional Chinese medicine (TCM) were randomly assigned to two groups with 1:1 radio. Children in the test group received QXQJ oral solution and oseltamivir simulant, while the control group received oseltamivir phosphate granules and QXQJ simulant. The duration of treatment was five days, followed by a two-day follow-up period. The primary endpoint was the clinical recovery time. Secondary endpoints included the time to defervescence, incidences of complications and severe or critical influenza, negative conversion rate, improvement of TCM syndromes, and safety profiles of the therapeutics, which mainly contained the adverse clinical events and adverse drug reactions. RESULTS: A total of 231 children were randomized to either the QXQJ (n=117) or oseltamivir (n=114) group. The FAS and PPS results showed that both groups experienced a median clinical recovery time of three days (P>0.05). The median time to defervescence of both groups were 36 hours in FAS and PPS (P>0.05), and two groups did not differ in terms of the other secondary endpoints (P>0.05). 14 patients (12.39%) in the QXQJ group and 14 patients (12.50%) in the oseltamivir group reported at least one adverse event, respectively. One serious adverse event occurred in the QXQJ group. There was no significant difference in the incidence of adverse events or adverse drug reactions between the groups. CONCLUSIONS: The efficacy of QXQJ oral solution was comparable to that of oseltamivir for treating influenza in children, with an acceptable safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021060.

BackgroundAchieving pathologic complete response (pCR) because of neoadjuvant therapy has been correlated with long-term clinical benefit, however, luminal-like tumors achieve a lower rate of pCR in comparison with other subtypes. The Shanghai Pudong (SHPD) 002 trial compares neoadjuvant chemotherapy concurrently with or with different estrogen deprivation therapy separately in premenopausal and postmenopausal patients with locally advanced breast cancer. MethodsIn this prospective, multicentre, neoadjuvant, phase III trial, 236 patients with locally advanced breast cancer were randomly assigned (2:1) to receive neoadjuvant chemotherapy (NCT) with gonadotropin-releasing hormone agonist (GnRHa) in premenopausal women or letrozole in postmenopausal women compared with chemotherapy alone. The primary endpoint was pCR (ypT0/is/ypN0). Secondary endpoints included disease-free survival, overall survival, and safety. This trial is registered with ClinicalTrials.gov, number NCT NCT02221999.Results A total of 236 patients were included. pCR was achieved by 20.4% in the chemotherapy plus ET group and 38.6% in the chemotherapy group. In postmenopausal patients, pCR was observed in 22.6% when treated with letrozole, 32.4% with NCT alone (p=0.276). Premenopausal patients with NCT and GnRHa achieved a significantly lower pCR of 18.8% than those of 42.9% in patients with NCT alone(p=0.003). A posthoc analysis showed CPS+EG score 0-3 was significantly more probable in patients with GnRHa (OR, 0.245; 95% CI, 0.072 to 0.832, P=0.024) than in those without GnRHa in the premenopausal patients who didn’t achieve near-pCR. After a median follow-up of 45 months, there was no significant difference concerning disease-free survival (DFS) (p=0.874) or overall survival (OS) (P =0.947) between the 2 postmenopausal groups. GnRHas significantly improved survival outcome in premenopausal patients (3-year OS, 100% with GnRHas, vs 88.2% without; log-rank p=0.034). Improved DFS (log-rank p = 0.001) and OS (log-rank p=0.003) were strongly associated with pCPS+EG score and GnRHa usage in premenopausal patients.ConclusionsConcurrent administration of GnRHas during neoadjuvant chemotherapy improves OS in premenopausal patients, though it does not increase the pCR rate. The adoption of the CPS+EG score may be a better surrogate endpoint for survival outcomes. The addition of letrozole to neoadjuvant chemotherapy confers no therapeutic advantage in terms of tumor response or survival outcome. Citation Format: Liheng Zhou, Shuguang Xu, Xiaohong Xue, Yinzhou Zhang, Bei Gu, Baoxing Lin, Junwen Bai, Hongwei Zhang, Kejin Wu, Yanping Lin, Yumei Ye, Yueyao Du, Xiaonan Sheng, Yaqian Xu, Jie Zhang, Wenjin Yin, Jinsong Lu. Efficacy, safety and survival of neoadjuvant chemotherapy with different estrogen deprivation stratified by menstrual status versus chemotherapy alone in locally advanced breast cancer (SHPD002)—— A randomized multicentre, open-label, phase 3 Triab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-02.

CYP2D6 gene polymorphism has a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancer. However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. We conducted a retrospective study in breast cancer patients to investigate the impact of CYP2D6 metabolic status on liver dysfunction events, gynecological events and dyslipidemia events. According to CYP2D6*10 (100C → T) genotype, the enrolled patients were further categorized into four cohorts (extensive metabolizers taking tamoxifen [EM + TAM], extensive metabolizers taking toremifene [EM + TOR], intermediate metabolizers taking tamoxifen [IM + TAM], and intermediate metabolizers taking toremifene [IM + TOR]). A total of 192 patients were included in the study, with a median follow-up time of 26.2 months. In EM + TAM cohort, the risks of liver dysfunction events (P = .004) and gynecological events (P = .004) were significantly higher compared to EM + TOR cohort. In IM + TAM cohort, the risks of liver dysfunction events (P = .14) and gynecological events (P = .99) were not significantly different from IM + TOR cohort. A significant decrease of total cholesterol was observed in EM + TAM cohort around 1 year after taking tamoxifen (P .001). Significant interactions between CYP2D6 metabolic status and endocrine agents were observed in terms of liver dysfunction events (P-interaction = .007) and gynecological events (P-interaction = .026). These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene.

Learners in connectivist learning are diverse. It’s necessary to make a clear understanding of learners’ participation types and characteristics for optimizing the learning support service and lear...

BackgroundWe sought to explore the impact of changing treatment strategy based on circulating tumor cells (CTC) on postoperative survival of breast cancer.MethodsWe retrospectively analyzed records of patients who underwent surgery for early-stage breast cancer at Beijing Friendship Hospital from January 2016 to January 2018 and regularly underwent CTC examination after surgery. During the regular examination and CTC monitoring, the patients with positive CTC results and without distant metastasis had their treatment regimen changed.ResultsOf 109 patients who received CTC examination regularly after surgery, 61 (56.0%) were CTC-positive during postoperative follow-up, including 33 ER or PR-positive, and 28 ER and PR-negative patients. Of the 33 ER or PR-positive patients, 20 changed endocrine therapy drugs. Compared with those without replacement, those with changed endocrine therapy strategy had higher CTC clearance rates (90.0% vs. 53.8%, p=0.04) and significantly lower CTC-positive values (1.70 ± 1.72 vs. 0.62 ± 0.65, p = 0.04). Among the 28 patients who were CTC positive and ER and PR-negative, 11 used capecitabine. Compared with non-users, the capecitabine users had higher CTC clearance rates (100.0% vs. 52.9%, p=0.01) and more significant decrease in CTC-positive values (2.09 ± 1.14 vs. 0.82 ± 1.67, p=0.04). Disease-free survival (DFS) at 1, 3, and 5 years was significantly longer in those who changed treatment than in those who did not (respectively, 96.6% vs. 89.6%, 92.8% vs. 56.9%, 69.0% vs. 47.8%, pConclusionTimely change of treatment strategy for breast cancer patients with positive CTC results after surgery may improve CTC clearance rate and DFS.

Dobutamine (DOB) is recommended as an inotrope for septic patients with low cardiac output, but its long-term impact on sepsis-induced cardiomyopathy remains unclear. This study investigated the long-term effect of DOB on septic myocardial dysfunction and injury. Rats were exposed to cecal ligation and puncture (CLP), the intrinsic myocardial function, other organ functions, hemodynamics, inflammatory response, serum myocardial injury biomarkers, myocardial apoptosis, and vascular permeability were determined. At 6 h after CLP, the left ventricular ±dP/dt were significantly depressed, cardiac tumor necrosis factor-α and vascular cell adhesion molecule-1 expression were increased, but not serum cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), creatinine, and urea nitrogen concentrations in CLP group compared with controls. At 9 h after CLP, hepatic dysfunction was present in CLP rats compared with controls. At 6 h after CLP, DOB treatment did not affect hemodynamics, the left ventricular ±dP/dt, cytokine levels in serum and myocardium, as well as cardiomyocyte apoptosis and cardiac vascular hyperpermeability at 20 h after CLP. However, DOB (10.0 μg/kg) increased serum IL-10 level and improved survival in septic rats. These results indicate that the intrinsic myocardial depression occurs earlier than hepatic and renal dysfunction in sepsis and serum cTnI, NT-proBNP, and H-FABP are not suitable as early biomarkers for sepsis-induced myocardial dysfunction. Although DOB treatment (10.0 μg/kg) in the presence of myocardial dysfunction improves survival in septic rats, it neither improves myocardial function and hemodynamics nor attenuates myocardial injury at the later stage of sepsis.

Cerebral ischemia-reperfusion injury (CIRI) is common in ischemic stroke and seriously affects the prognosis of patients. At present, N

Background and ObjectivesParkinson’s disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC).MethodsPeripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining.ResultsHere we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets.ConclusionsThese results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.

Parkinson’s disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. When the groups were stratified by their T cell responsiveness to alpha-synuclein (α-syn) as a proxy for an ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. We identified significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5, and CCR1. In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin. Together, these findings suggest that features of circulating T cells with α-syn-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets.

Background and objectivesParkinson's disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC).MethodsPeripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining.ResultsHere we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets.ConclusionsThese results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.

Static electric field (SEF) from ultra-high-voltage direct-current (UHVDC) transmission lines has the potential to produce neurobiological effects. To explore these effects and elucidate their potential mechanisms, protein expression levels and morphological structure in the hippocampi of mice were investigated after SEF exposure. Mice from the Institute of Cancer Research were exposed to an environmental SEF induced by UHVDC transmission lines with the strength of 9.20–21.85[Formula: see text]kV/m for 35 days. Mouse body weight was measured weekly during the exposure. After the exposure, hippocampal Ca[Formula: see text]/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) expression levels were assayed by Western blot. Hippocampal pathologic morphology and ultrastructure were observed using light microscopy and transmission electron microscopy, respectively. No significant differences in body weight, CaMKII and CaN expression levels, and hippocampal pathologic morphology were observed between mice in the exposed and the control groups. However, cytoplasmic vacuolization of the hippocampal neurons was observed in the exposed group. Thus, hippocampal neuron ultrastructure damage may be a mechanism of SEF-exposure-induced memory decline in mice.

Objective To investigate the expression of Linc00342 in peripheral blood lymphocytes in patients with chronic kidney disease (CKD) and healthy people and to identify Linc00342 as a biomarker of chronic kidney disease. Methods Peripheral blood samples were collected from 30 patients with chronic kidney disease and 10 healthy volunteers at the First Affiliated Hospital of Bengbu Medical College, China. According to CKD classification, the patients were divided into three CKD groups (the CKD1/2 group, CKD3/4 group and CKD5 group) and a healthy volunteer group (the H group). The relative expression of Linc00342 in lymphocytes was detected by RT-PCR, while the IL-6 and IL-10 levels in the serum were detected by ELISA. In addition, the general data of the patients and healthy volunteers were recorded. Finally, SPSS software was used for statistical analysis. Results The expression level of Linc00342 in the peripheral blood lymphocytes of the four groups increased significantly as the CKD grade increased, and there were statistically significant differences (p < 0.01). There was a positive linear correlation between the expression of Linc00342 in peripheral blood lymphocytes and the eGFR (p < 0.05), which was expressed by the linear model equation: Y = 2.532 + 0.012X. Among the inflammatory factors for the early diagnosis of CKD, the area under the ROC curve for the expression of Linc00342 in peripheral blood lymphocyte was 0.953, the standard error was 0.034 and the 95% confidence interval was 0.000-1.000. Conclusion The expression level of Linc00342 in peripheral blood lymphocytes can reflect the severity of CKD, and Linc00342 is possibly used as a molecular marker of CKD.

Aim: To systematically profile and characterize the circular RNA (circRNA) expression pattern in estrogen receptor (ER)-positive breast cancer (BC). Materials & methods: CircRNA expression profile was performed in ER-positive BC and adjacent nontumor tissues. The differentially expressed circRNAs (DECs) was analyzed by bioinformatics. The analysis findings were validated by quantitative real-time PCR. Results: In total, 3653 DECs were detected in our ER-positive BC compared with the control. Bioinformatics analysis showed that some pathways related to cancer, especially BC, were significantly enriched. Additionally, hsa_circ_0087378 was validated to be downregulated in ER-positive BC and the hsa_circ_0087378-miR-1260b-SFRP1 axis was proposed to be a key regulatory pathway. Conclusion: This study revealed the general expression characteristics of specific DECs in ER-positive BC and hsa_circ_0087378 might be a promising candidate target.

Background With the explosion of COVID-19 globally, it was unclear if people with Parkinson’s disease (PD) were at increased risk for severe manifestations or negative outcomes. Objectives To report on people with PD who had suspected or confirmed COVID-19 to understand how COVID-19 manifested in PD patients. Methods We surveyed PD patients who reported COVID-19 to their Movement Disorders specialists at Columbia University Irving Medical Center and respondents from an online survey administered by the Parkinson’s Foundation that assessed COVID-19 symptoms, general clinical outcomes and changes in motor and non-motor PD symptoms. Results Forty-six participants with PD and COVID-19 were enrolled. Similar to the general population, the manifestations of COVID-19 among people with PD were heterogeneous ranging from asymptomatic carriers (1/46) to death (6/46). The most commonly reported COVID-19 symptoms were fever/chills, fatigue, cough, weight loss, and muscle pain. Worsening and new onset of motor and non-motor PD symptoms during COVID-19 illness were also reported, including dyskinesia, rigidity, balance disturbances, anxiety, depression, and insomnia. Conclusion We did not find sufficient evidence that PD is an independent risk factor for severe COVID-19 and death. Larger studies with controls are required to understand this further. Longitudinal follow-up of these participants will allow for observation of possible long-term effects of COVID-19 in PD patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10784-3.

Background: Homologous recombination repair gene mutations are associated with increased platinum-based chemosensitivity, whereas few studies have reported the predictive value of family history of cancer for breast cancer in the neoadjuvant setting. This study aimed to construct a brief and effective novel family history scoring system and explore its association with pathological complete response (pCR), survival outcomes, and safety for locally advanced breast cancer receiving platinum-based neoadjuvant chemotherapy. Methods: A total of 262 patients treated with neoadjuvant cisplatin and paclitaxel were included. Neo-Family History Score (NeoFHS) was calculated according to cancer type, age at diagnosis, kinship, and number of affected relatives. Logistic regression was performed to analyze the association between pCR and NeoFHS. Survival rates were compared by Kaplan-Meier curves, examined by log-rank test and Cox proportional hazard regressions. Results: For all patients enrolled in this study, clinical tumor stage (p=0·048), estrogen receptor status (p=0·001), progesterone receptor status (p=0·036), human epidermal growth factor receptor 2 (HER2) status (p=0·013), and molecular subtype (p=0·016) were significantly related to NeoFHS. The multivariate logistic regression revealed that NeoFHS is an independent predictive factor of pCR (OR=2·262, 95% CI 1·159-4·414, p=0·017), especially in node-positive (OR=3·088, 95% CI 1·498-6·367, p=0·002), hormone receptor-positive (OR=2·645, 95% CI 1·164-6·010, p=0·020), and HER2-negative subgroups (OR=4·786, 95% CI 1·550-14·775, p=0·006). Kaplan-Meier estimates suggested that NeoFHS could serve as an independent prognostic factor for relapse-free survival in the whole group (adjusted HR=0·305, 95% CI 0·102-0·910, p=0·033) and node-positive subgroup (adjusted HR=0·317, 95% CI 0·103-0·973, p=0·045). Furthermore, alopecia (p=0·001), nausea (p=0·001), peripheral neuropathy (p=0·018), diarrhea (p=0·026), constipation (p=0·037) of any grade and leukopenia of grade 3 or greater (p=0·005) were more common in patients with higher NeoFHS. Conclusions: Our study revealed that NeoFHS is a practical and effective biomarker for predicting not only pCR and survival outcomes but also chemotherapy-induced AEs for neoadjuvant platinum-based chemotherapy for breast cancer. It may help screen candidate responders and guide safety managements in the future. Trial Registrion: SHPD001 (ClinicalTrials.gov identifier: NCT02199418) and SHPD002 (ClinicalTrials.gov identifier: NCT02221999). Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Shanghai Natural Science Foundation [grant numbers 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant numbers 2018-15 and 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49 and ZH2018QNA42], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01 and PY2018-III-15], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty Declaration of Interest: None to declare. Ethical Approval: Ethical approvals were granted for both trials by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University.

The thermal structure in reservoirs affects the development of aquatic ecosystems and is substantially influenced by changing climate conditions. At the same time, reservoir management strategies can also affect the thermal structure of the water body and may enable adaptation strategies in a warmer world. We applied a two-dimensional hydrodynamicmodel to explore the response of the thermal structure in Germany's largest drinking water reservoir, Rappbode Reservoir, to future climate projections and different water withdrawal strategies. We used projections for representative concentration pathways (RCP) 2.6, 6.0 and 8.5 from an ensemble of 4 different global climate models taken from the ISIMIP project. Simulation results showed that epilimnetic water temperatures in the reservoir strongly increased under all three climate scenarios while the magnitude of warming directly corresponds to the increase in air temperatures. Hypolimnetic temperatures remained rather constant under RCP 2.6 and RCP 6.0 but increased markedly under RCP 8.5. Under the intense warming in RCP 8.5, hypolimnion temperatures were projected to rise from 5 °C to 8 °C by the end of the century. Moreover, the results suggested that surface withdrawal can be an effective adaptation strategy under strong climate warming (RCP 8.5) to reduce surface warming and even avoid hypolimnetic warming. This study documents how global scale climate projections can be translated into site-specific climate impacts to derive adaptation strategies for reservoir operation. Moreover, our results illustrate that the most intense warming scenario, i.e. RCP 8.5, demands far-reaching climate adaptation while the mitigation scenario (RCP 2.6) does not require adaptation of reservoir management before 2100.

As the COVID-19 pandemic continues to affect the international community, very little is known about its impact on the health and day-to-day activities of people with Parkinson’s disease (PwPD). To better understand the emotional and behavioral consequences of the public health policies implemented to mitigate the spread of SARS-CoV-2 in PwPD, and to explore the factors contributing to accessing alternative health care mechanisms, such as telehealth, we administered an anonymous knowledge, attitude, and practice survey to PwPD and care partners, via the mailing lists of the Parkinson’s Foundation and Columbia University Parkinson’s Disease Center of Excellence with an average response rate of 19.3%. Sufficient information was provided by 1,342 PwPD to be included in the final analysis. Approximately half of respondents reported a negative change in PD symptoms, with 45–66% reporting mood disturbances. Telehealth use increased from 9.7% prior to the pandemic to 63.5% during the pandemic. Higher income and higher education were associated with telehealth use. Services were more often used for doctor’s appointment than physical, occupational, speech, or mental health therapies. Almost half (46%) of PwPD preferred to continue using telehealth always or sometimes after the coronavirus outbreak had ended. Having received support/instruction for telehealth and having a care partner, friend, or family member to help them with the telehealth visit increased the likelihood of continuous use of telehealth after the pandemic ended. Taken together, PD symptoms and management practices were markedly affected by COVID-19. Given the observed demographic limitations of telehealth, expanding its implementation to include additional physical, occupational, psychological, and speech therapies, increasing support for telehealth, as well as reaching underserved (low income) populations is urgently required.

In recent years, deep convolutional neural networks (CNNs) have achieved great success in computer vision tasks. However, they are often perceived as "black box" methods for the lack of interpretability. In this work, we propose an approach to alleviate the opaqueness of deep learning models by providing visual explanations to the predictions of the network. Our approach entitled Attention Backpropagation will backpropagate the network's attention to produce an attention map highlighting the important regions in the image for predicting. This is a generalized method that can be used for all the networks without modification of the network architecture or retraining. We apply the proposed approach to provide visual explanations for the whole inference process of VGG-16 model, and analyze the cause for the erroneous predictions. Furthermore, numerical results suggest that our approach has better ability to localize the discriminative image regions, and outperforms previous methods in weakly-supervised localization task and the pointing game test on ILSVRC-15 dataset.

Background Recent evidence shows that inducing ferroptosis may improve efficacy of tumor therapy. However, ferroptosis-related genes have been little studied in patients with breast cancer especially in the neoadjuvant setting. ACSL4 and GPX4 have been well established as the positive and negative regulator of ferroptosis, respectively. This study aimed to explore the predictive value of ACSL4 and GPX4 for patients with breast cancer administered neoadjuvant chemotherapy. Methods This study included patients treated with paclitaxel-cisplatin-based neoadjuvant chemotherapy. Immunohistochemistry staining of ACSL4 and GPX4 was carried out on the core needle biopsy specimens. Logistic regression was performed to explore the predictive biomarkers of pathological complete response (pCR). Survival analyses were examined by log-rank test and Cox proportional hazard regression. Findings A total of 199 patients were included for the analyses. Both ACSL4 expression and ACSL4/GPX4 combination status could serve as independent predictive factors for pCR. The interaction for pCR was observed between ACSL4 and clinical tumor stage. Besides, ACSL4 expression, GPX4 expression, and their combination status were independent prognostic factors for disease-free survival. Analyses of the Kaplan-Meier Plotter database suggested that higher ACSL4 expression is related to better overall survival, and higher GPX4 expression is related to better distant metastasis-free survival. Pathway analyses revealed that ACSL4 and GPX4 might function in crucial pathways including apoptosis, autophagy, cell adhesion, lipid metabolism, etc. Interpretation This study revealed the critical value of ACSL4 and GPX4 serving as novel predictive and prognostic biomarkers for patients with breast cancer receiving neoadjuvant chemotherapy. It might be a novel strategy to induce ferroptosis to promote chemosensitivity. Future studies are required to elucidate the potential mechanisms. Funding This work was supported by Shanghai Natural Science Foundation [grant number 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B, and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Youth Medical Talents - Specialist Program [grant number 2018-15], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant number 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49, ZH2018QNA42, and YG2019QNA28], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01, PY2018-III-15, and PYIII20-09], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty.

Design for collaborative learning in Massive Open Online Courses (MOOCs) is considered more challenging compared to another context, while the benefits are huge for learners to collaborate in MOOC, especially connectivism MOOC (cMOOC), where learning is to connect specialized nodes (learners) or information sources. This study based on a cMOOC with 2791 participants, aimed to build a platform for conversation and problem-solving among researchers and practitioners, in the field of educational technology. And this paper investigated the learning process of a high-performance collaborative learning group in a cMOOC by analyzing their blogs, artifacts to record and report learning formatively. We discovered that the group demonstrated strategies including keeping the balance between student agency and problem quality, building up trust and commitment, keeping an artifact to manifest thinking, and making each individual recognized, which could help inform future design for collaborative learning in MOOC.

A novel fluorine-doped TiO

Background: a2A adrenoceptor receptor (a2A-AR) plays an important role in inflammatory response in Kupffer cells in sepsis. Blockage of a2A-AR inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor a (TNF-a) production and protects the target organ functions in sepsis animal models; however, its expression and function in microglia have remained obscure. This study aimed to determine whether a2A-AR was expressed in microglia and whether its activation would exacerbate microglial inflammation and sepsis-related neurological dysfunction. Methods: Western blotting and immunofluorescence were used to detect a2A-AR expression in BV-2 microglia. Enzyme-linked immunosorbent assay (ELISA) was used to assess the TNF-a production in the supernatant after LPS induced BV-2 cells were pretreated with a2A-AR agonist BHT933, and/or a2A-AR antagonist BRL44408, and also in the supernatants derived from BV-2 cells treated with BHT933 and/or PKC inhibitor. Signaling pathways including JNK，P38，ERK，IκBa, CREB and PCK were detected by western blotting. a2A-AR gene knock-out (KO) and wild type (WT) mice were prepared by intraperitoneal injection of LPS. Lectin /TNF-a labeled microglia and synaptophysin/NeuN expression in the hippocampus were localized by immunofluorescence. Morris water maze test, Rotating-stick test, Elevated plus maze test and Open-field test were conducted over 4 weeks.Results: a2A-AR was constitutively expressed in BV-2 microglia, which was enhanced by LPS. Pretreatment with BHT933 promoted LPS-induced IκB and JNK phosphorylation, and TNF-a secretion in BV-2 microglia which were abrogated by BRL44408. Activation of a2A-AR by BHT933 also increased PKC phosphorylation in LPS-treated BV-2 microglia. PKC inhibitor significantly reversed the promoting effects of BHT933 on IκB and JNK phosphorylation as well as TNF-a secretion in LPS-treated BV-2 microglia. Furthermore, LPS treatment significantly increased hippocampal microglia activation and TNF-a expression, decreased hippocampal synaptophysin expression, and impaired cognitive and motor functions in WT mice, all of which were markedly reversed by a2A-AR gene knockout. Conclusion: a2A-AR activation promotes LPS-induced IκB and JNK phosphorylation as well as TNF-a production in microglia through the PKC signaling pathway. Knockout of a2A-AR gene significantly improves LPS-induced cognitive and motor impairments in mice, indicating that a2A-AR is a potential therapeutic target for sepsis-associated encephalopathy.

Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.

Supplemental material, Supplementary_Materials_-_description for Predictive and prognostic value of EPIC1 in patients with breast cancer receiving neoadjuvant chemotherapy by Yaqian Xu, Yan Wang, Chenwei Yuan, Xiaonan Sheng, Rui Sha, Huijuan Dai, Shan Zhang, Yaohui Wang, Yanping Lin, Liheng Zhou, Shuguang Xu, Jie Zhang, Wenjin Yin and Jinsong Lu in Therapeutic Advances in Medical Oncology

Background: Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Methods: The concentration of sphingosine 1-phosphate (S1P) was detected by high-performance liquid chromatography-tandem mass spectrometry. The Oxygen consumption rate was measured by XF96 metabolic flux analyzer. The interaction between TIM and Specificity protein 1 (Sp1) was confirmed by Co-immunoprecipitation. Chromatin immunoprecipitation and luciferase report assay were performed to demonstrate whether SP1 binds on the Alkaline Ceramidase 2 (ACER2) promotor. Findings: The expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with Sp1 which contributes to upregulate the expression of ACER2. Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Interpretation: Our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81672358, No. 81802890, No. 81172505, No. 81302302). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The SHPD001 and SHPD002 trials were approved by the Independent Ethical Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Before enrollment, all patients signed written informed consent. All animal experiments were approved by the Institutional Animal Care and Use Committee of East China Normal University.

With the rapid development of ultra-high-voltage direct-current (UHVDC) transmission, the strength of environmental static electric field (SEF) around UHVDC transmission lines increased substantially, which has aroused widely public attention on the potential health effects of SEF. In this study, the effect of SEF exposure on learning and memory ability was investigated. Institute of Cancer Research mice were exposed to 56.3 kV/m SEF for a short term (7 days) or long term (49 days). Behaviors in the Morris water maze (MWM) test, hippocampal neurotransmitter contents, and oxidative stress indicators were examined. Results showed that short-term SEF exposure significantly prolonged escape latency and decreased the number of platform-site crossovers, as well as decreased the time spent in the target quadrant in the MWM test. Meanwhile, serotonin level and the ratio of glutamate level to γ-aminobutyric acid level changed significantly. Besides, malondialdehyde content and glutathione peroxidase activity increased significantly, while superoxide dismutase activity decreased significantly. After long-term SEF exposure, all indices above showed no significant differences between the SEF and sham exposure groups. These data indicated that short-term exposure to 56.3 kV/m SEF could cause abnormal neurotransmitter levels and oxidative stress in the hippocampus, which led to the decline in learning and memory ability. Under the condition of long-term exposure, the SEF-induced disturbances in neurotransmitter contents and redox balance were offset by the compensatory responses of mice, and thus, the learning and memory ability returned to normal level. The temporary and reversible decline in learning and memory ability was only a common biological effect of SEF rather than a health hazard.

Background Homologous recombination deficiency is associated with platinum-based chemosensitivity, whereas few studies reported the predictive value of family history of cancer for breast cancer in the neoadjuvant setting. This study aimed to construct a novel family history scoring system and to explore its association with clinical outcomes for patients with breast cancer receiving neoadjuvant platinum-based chemotherapy. Methods This study included 262 patients with locally advanced breast cancer enrolled in the SHPD001 and SHPD002 trials from October 2013 to June 2018. The Neo-Family History Score (NeoFHS) was calculated according to cancer type, age at diagnosis, kinship, and number of affected relatives. Findings Clinical tumor stage (p=0·048), estrogen receptor status (p=0·001), progesterone receptor status (p=0·036), human epidermal growth factor receptor 2 status (p=0·013), and molecular subtype (p=0·016) were significantly related to NeoFHS. NeoFHS could serve as an independent predictive factor of pathological complete response (pCR) (OR=2·262, 95% CI 1·159-4·414, p=0·017) and an independent prognostic factor of relapse-free survival (adjusted HR=0·305, 95% CI 0·102-0·910, p=0·033). Alopecia (p=0·001), nausea (p=0·001), peripheral neuropathy (p=0·018), diarrhea (p=0·026), constipation (p=0·037) of any grade and leukopenia of grade 3 or greater (p=0·005) were more common in patients with higher NeoFHS. Interpretation NeoFHS is a practical and effective biomarker for predicting not only pCR and survival outcomes but also chemotherapy-induced adverse events for neoadjuvant platinum-based chemotherapy in breast cancer. It may help screen candidate responders and guide safety managements. Funding Shanghai Natural Science Foundation [grant number 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B, and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Youth Medical Talents - Specialist Program [grant number 2018-15], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant number 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49, ZH2018QNA42, and YG2019QNA28], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01, PY2018-III-15, and PYIII20-09], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shanghai Municipal Key Clinical Specialty.

Uric acid (UA) is a natural antioxidant and iron scavenger in the human body, which has been hypothesized to exert an anti-oxidative effect in Parkinson’s disease (PD). This study aimed to investigate the relationship between serum UA levels and freezing of gait (FOG) in PD. A total of 321 Chinese PD patients with fasting serum UA evaluated were included in the cross-sectional study. Demographics, clinical features, and therapeutic regimen were collected. The Unified PD Rating Scale (UPDRS) III and Hoehn and Yahr (H and Y) stage were used to evaluate the severity of disease, and the Frontal Assessment Battery (FAB) and Montreal Cognitive Assessment (MoCA) scales were used to assess the cognitive function. Patients with FOG showed lower proportion of male, longer disease duration, lower body mass index, lower concentrations of serum UA, higher total levodopa equivalent daily dosage, higher UPDRS III score, greater median H and Y stage, lower scores of FAB and MoCA, and higher frequencies of motor fluctuation, dyskinesia, falls, and festination compared to patients without FOG (P

With the rapid development of traffic facilities in China, traffic noise pollution is increasingly prominent. This research aims to explore the influences of combined traffic noise on receptors' anxiety. Institute of cancer research mice were exposed to combined traffic noise (CTN) from highway and high-speed railway for 52days, whose day-night equivalent continuous A-weighted sound pressure level (Ldn) was 70dB(A). The impacts of CTN on anxiety were explored by behavior tests and monoamine neurotransmitter assays. The results were in depth discussed in comparison to two previous studies on the impacts of single high-speed railway noise (HSRN) and aircraft noise (AN), but data from the three studies were not merged and statistically compared. No significant differences were shown in the behavioral indicators and the monoamine levels between the experimental and control groups after CTN exposure, indicating no obvious impacts of 70dB(A) CTN on anxiety in mice were found in this study. When Ldn was approximately 70dB(A), CTN had less obvious impacts on anxiety than HSRN and AN, which is mainly related to that both the acoustical parameters of noise events [maximum noise level (LAmax), noise events duration, slope of rise, difference of LAmax from 1-min background equivalent continuous A-weighted sound pressure level] and modified day-night equivalent continuous R-weighted sound pressure level (considering animal auditory sensitivity to different sound frequencies and circadian rhythms) of CTN are smaller than those of HSRN and AN.

The image blur assessment is of various practical use such as feedback of microscope dynamic focusing and assessment of the quality of pictures in social media. However, the problem of providing a fast and sensitive assessment toward image blur is not easy to deal with. In this paper, we provide a new effective way to evaluate the blur level of the image. We first introduce Markov Constraints to the Fuzzy-C-Means (MC-FCM) clustering algorithm to improve the robustness to noise, then obtain the fuzzy membership of pixels via the MC-FCM, finally, to leverage fuzzy membership from MC-FCM, the blur assessment toward pixels in the edge zone is provided by modifying Shannon’s entropy. Comparisons are made on two public blur image database over five recent image blur assessment algorithms. The results demonstrate that the proposed algorithm has better resolutions for mildly blurred images and lower computation complexity compared with existing approaches.

Accurate and low-cost indoor localization continues to be a research challenge. The emerging communication technologies in 5G and 802.11 standards (e.g., 802.11n and 802.11 ac), such as massive MIMO and mmWave, provide opportunities for accurate indoor localization. Meanwhile, location information is also critical for the development of new technologies, e.g., directional communication using beamforming. It leads to a synergistic relationship between localization and communication. In this paper, we review the potential benefits of the emerging communication technologies (i.e., smart antennas, Massive MIMO, mmWave, beamforming, CSI) for indoor localization. It may provide a useful guide for researchers who are interested in developing indoor localization systems based on emerging communication technologies.

In order to investigate the noise impacts of wind turbines with a high single-machine capacity (2 MW) on the residents living around, a face-to-face questionnaire survey was conducted. The moderating factors of noise annoyance, noise exposure–response relationships as well as noise impacts on sleep and self-reported health were investigated. Results showed that noise sensitivity, attitude towards wind turbines’ visual impact on the landscape, general opinion on wind turbines and noise intensity had statistically significant impacts on annoyance due to wind turbine noise. Compared with wind turbines with lower single-machine capacity in relevant studies, those with higher single-machine capacity in this study induced higher annoyance at the same Lden, which was relative to the visibility of wind turbines, background noise levels of wind farm area, etc. Noise sensitivity, noise annoyance and noise intensity, which had no significant correlation with self-reported health effects, were statistically significantly correlated with sleep disturbance on respondents.

With the rapid development of high voltage direct current transmission, the possibility of health effects associated with static electric field (SEF) has caused wide public concern. To examine the effects of long-lasting, full-body exposure to SEF on cognition, Institute of Cancer Research mice were exposed to SEF for 35 d. The intensities of SEF in experimental group I (EG-I), experimental group II (EG-II) and control group (CG) were 2.30∼15.40 kV/m, 9.20∼21.85 kV/m and 0 kV/m, respectively. The performance in learning and memory of mice were tested by Morris water maze (MWM) on days 2∼6, 16∼20 and 30∼34 during the exposure period. The concentrations of hippocampal amino acid neurotransmitters were evaluated on days 7, 21 and 35. Results showed that the latency in the MWM test had no significant difference among the EG-I, EG-II and CG (P > 0.05) during the exposure period. The percentage of time spent in the target quadrant was significantly decreased in the EG-II on day 34 during the exposure period (P < 0.05), whereas the percentage of time spent in the opposite quadrant increased markedly (P < 0.01). The glutamate and gamma-aminobutyric acid concentrations showed no significant differences among the EG-I, EG-II and CG (P > 0.05) during the exposure period. These results indicated that long-lasting, full-body exposure to SEF with certain intensity would not cause significant influence on learning ability, but it might associate with memory impairment of receptors. Meanwhile, this effect of memory impairment was dose-dependent and not causally linked to the glutamate and gamma-aminobutyric acid levels in the hippocampus.

Background The association between the polymorphism rs3794087 in the solute carrier family 1, member 2 ( SLC1A2 ) and the risk of essential tremor (ET) among different studies is controversial. Considering the overlap of the clinical manifestations and pathological characteristics of ET, Parkinson's disease (PD), multiple system atrophy (MSA), as well as amyotrophic lateral sclerosis (ALS), we explored the possible genetic association of rs3794087 with ET, PD, MSA and ALS in a Chinese cohort. Methods A total of 112 ET, 621 PD, 356 MSA, 513 sporadic ALS (SALS) patients and 437 healthy controls (HCs) were genotyped for rs3794087 using the Sequenom iPLEX Assay technology. Results Significant association was found between SLC1A2 rs3794087 and PD in the additive model ( p = 0.006), which was more obvious in early onset PD. The minor allele of rs3794087 decreased the risk for early onset PD ( p = 0.011, OR: 0.73, 95% CI: 0.56–0.94). However, no significant differences in the genotype distributions and allele frequency were observed in the allelic, additive, dominant or recessive genetic models of SLC1A2 rs3794087 between ET patients and HCs, between SALS patients and HCs, and between MSA and HCs. Conclusions Our results suggested SLC1A2 rs3794087 may decrease the risk for PD in a Chinese cohort, but do not support a role in the susceptibility to SALS or MSA.

Background The rs156429 polymorphism in the glycoprotein nonmetastatic melanoma protein B (GPNMB) gene was found to be associated with the risk for Parkinson disease (PD) in Caucasian population by genome-wide association studies (GWAS). Recently, encoded protein, GPNMB, was identified as a novel neuro-protective factor in amyotrophic lateral sclerosis (ALS). The overlapping of clinical manifestations and pathologic characteristics among PD, ALS, and multiple system atrophy (MSA) are observed. Object This study aimed at investigating the possible associations of the polymorphism and the three neurodegenerative diseases: PD, ALS and MSA in a Chinese population. Methods All of the subjects, including PD (n = 1096), sporadic ALS (SALS) (n = 876) and MSA (n = 356) patients, and 829 health controls (HCs) were included. All subjects were genotyped for this polymorphism using Sequenom iPLEX Assay technology. Results No differences were found in the genotype distributions and minor allele frequency of GPNMB rs156429 between PD patients and HCs, between SALS patients and HCs, between MSA patients and HCs, and between subgroups of PD, ALS and MSA patients with regard to clinical features such as sex, age of onset, presence or absence of cognitive abnormality, depression and anxiety. Conclusion Lack of association identified in our study suggests that it may be premature to conclude associations between GPNMB rs156429 and SALS, PD and MSA. More studies on such an association involving a larger number of participants are needed to confirm the present findings.

With the rapid development of ultra high voltage alternating current (UHV AC) transmission, the intensity of environmental power frequency electric field (PFEF) near UHV AC transmission lines increased continuously, which has attracted considerable public attention on the potential health effects of PFEF. In this study, the effect of PFEF exposure on the kidney was explored. Institute of Cancer Research (ICR) mice were exposed to 35 kV/m PFEF (50 Hz). Two indicators relating to renal function (urea nitrogen and creatinine) were tested after the exposure of 7d, 14d, 21d, 35d and 49d. The pathological morphology and cellular ultrastructure of kidney were observed respectively by light microscopy and electron microscopy after the exposure of 25d and 52d. Results showed that compared with that of the control group, the concentration of urea nitrogen of 35 kV/m PFEF exposure group significantly increased on the 21st and 35th days, and the concentration of creatinine significantly increased on the 14th, 21st and 35th days. However, the concentrations of creatinine and urea nitrogen both returned to normal levels on the 49th day. Furthermore, an enlarged Bowman's space, the vacuolation of renal tubular epithelial cells and the foot process effacement of podocyte were found after 25d exposure, but no abnormality was observed after 52d exposure. Obviously, a short-term (35d) exposure of 35 kV/m PFEF could cause kidney injury, which could be recovered after a longer-term (52d) exposure. Based on this study and relevant literatures, one explanation for this two-way effect is as follows. Kidney injury was caused by the disequilibrium of mitochondrial dynamics under 35 kV/m PFEF exposure. PFEF could also activate Wnt/β-catenin signal to promote the recovery of renal tubular epithelial cells and glomerular podocytes, so kidney injury could be repaired.