Search

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. The proportion of late-onset ALS in China were low and may have distinct clinical and genetic manifestations. We aimed to investigate the natural history and remarkable psychiatric state of ALS with age at onset over 60 years in China.We collected all ALS cases from 2017 to 2020 in our center and focused on late-onset ALS patients particularly, by analyzing the clinical data, including the ALS onset and disease progression. Anxiety, depression, cognitive function, and sleep quality were assessed to reflect the psychiatric state.A total of 193 late-onset ALS patients were included in this study. The median age at onset of late-onset ALS was 65 years with the quartile from 62 to 68 years. When compared with 446 non-late-onset ALS, late-onset ALS showed distinct clinical presentation, with lower ALS Functional Rating Scale-Revised at diagnosis and faster rate of progression. Remarkably, late-onset ALS were suffering from worse psychiatric state, including serious anxiety and depression, as well as worse cognitive function with sleep quality. The abnormal psychiatric state was more pronounced in female patients of late-onset.In the current study, ALS patients with late-onset showed unique clinical features. Severe psychiatric conditions and faster progression in the early stage of the disease of late-onset ALS indicated the need for more social and psychiatric support in this population.

ObjectivesThere is significant burden on caregivers of patients with amyotrophic lateral sclerosis (ALS). However, only a few studies have focused on caregivers, and traditional research methods have obvious shortcomings in dealing with multiple influencing factors. This study was designed to explore influencing factors on caregiver burden among ALS patients and their caregivers from a new perspective.DesignCross-sectional study.SettingThe data were collected at an affiliated hospital in Guangzhou, Guangdong, China.ParticipantsFifty-seven pairs of patients with ALS and their caregivers were investigated by standardised questionnaires.Main outcome measuresThis study primarily assessed the influencing factor of caregiver burden including age, gender, education level, economic status, anxiety, depression, social support, fatigue, sleep quality and stage of disease through data mining. Statistical analysis was performed using SPSS 24.0, and least absolute shrinkage and selection operator (LASSO) regression model was established by Python 3.8.1 to minimise the effect of multicollinearity.ResultsAccording to LASSO regression model, we found 10 variables had weights. Among them, Milano-Torinos (MITOS) stage (0–1) had the highest weight (−12.235), followed by younger age group (−3.198), lower-educated group (2.136), fatigue (1.687) and social support (-0.455). Variables including sleep quality, anxiety, depression and sex (male) had moderate weights in this model. Economic status (common), economic status (better), household (city), household (village), educational level (high), sex (female), age (older) and MITOS stage (2–4) had a weight of zero.ConclusionsOur study demonstrates that the severity of ALS patients is the most influencing factor in caregiver burden. Caregivers of ALS patients may suffer less from caregiver burden when the patients are less severe, and the caregivers are younger. Low educational status could increase caregiver burden. Caregiver burden is positively correlated with the degree of fatigue and negatively correlated with social support. Hopefully, more attention should be paid to caregivers of ALS, and effective interventions can be developed to relieve this burden.

Klinefelter syndrome (KS) is the most common chromosome aneuploidy and a common cause of infertility in males. KS patients have at least one extra X chromosome, and about 80% of patients have the karyotype 47,XXY. Twenty percent of KS patients have higher-grade aneuploidies (48,XXXY, 48,XXYY, 49,XXXXY) and exert some clinical manifestation different from those with 47,XXY. Here we report the case of a young man who initially presented with diabetic ketosis and foot ulcer and was later diagnosed as having an extremely rare mosaic variant of KS (47,XXY/48,XXXY/49,XXXXY). Clinical and laboratory features are summarized. The patient developed a severe foot ulcer with an 18-month history of diabetes. Learning disability was noted since early childhood. The patient had typical manifestations of KS, including increased height, sparse beard and body hair, and small penis. He also had some characteristic features of patients with additional sex chromosomes, including epicanthal folds, narrow palpebral fissures, prominent elbows, and undescended testicles. Severe myopia and myopic macular degeneration was also found. Lab tests revealed low testosterone and elevated FSH but normal LH levels. Chromosome analysis on lymphocytes revealed an aberration of 47,XXY/48,XXXY/49,XXXXY. This case provides information on KS patients with the extremely rare karyotype 47,XXY/48,XXXY/49,XXXXY, and also emphasizes the importance of considering KS in the differential diagnosis of a sterile male with diabetes.

The slow loris (Genus Nycticebus) is a group of small, nocturnal and venomous primates with a distinctive locomotion mode. The detection of slow loris plays an important role in the subsequent individual identification and behavioral recognition and thus contributes to formulating targeted conservation strategies, particularly in reintroduction and post-release monitoring. However, fewer studies have been conducted on efficient and accurate detection methods of this endangered taxa. The traditional methods to detect the slow loris involve long-term observation or watching surveillance video repeatedly, which would involve manpower and be time consuming. Because humans cannot maintain a high degree of attention for a long time, they are also prone to making missed detections or false detections. Due to these observational challenges, using computer vision to detect slow loris presence and activity is desirable. This article establishes a novel target detection dataset based on monitoring videos of captive Bengal slow loris (N. bengalensis) from the wildlife rescue centers in Xishuangbanna and Pu’er, Yunnan, China. The dataset is used to test two improvement schemes based on the YOLOv5 network: (1) YOLOv5-CBAM + TC, the attention mechanism and deconvolution are introduced; (2) YOLOv5-SD, the small object detection layer is added. The results demonstrate that the YOLOv5-CBAM + TC effectively improves the detection effect. At the cost of increasing the model size by 0.6 MB, the precision rate, the recall rate and the mean average precision (mAP) are increased by 2.9%, 3.7% and 3.5%, respectively. The YOLOv5-CBAM + TC model can be used as an effective method to detect individual slow loris in a captive environment, which helps to realize slow loris face and posture recognition based on computer vision.

Prader-Willi Syndrome (PWS) is a rare autosomal dominant disorder on the 15q11.2-q13 chromosome. PWS may impact metabolic, endocrine, and neurologic systems and combine with hypotonia, sleep disturbances, cognitive disability, central adrenal insufficiency, hypothyroidism, hypogonadism, short stature, and other diseases. Here ,we report a PWS patient with secondary diabetes mellitus. Clinical and laboratory features are summarized. The patient had typical manifestations of PWS including almond-shaped eyes, narrow temples, narrow nasal bridge, and short hands and feet. Lab test revealed hypogonadism and growth hormone deficiency. SNP array revealed one copy of chromosome 15 q11.2q13.1 was missing, with a length of about 6.4 mbp. This case emphasizes the importance of considering PWS in the differential diagnosis of an adolescent with diabetes. Antenatal history of neonatal hypotonia and childhood history of feeding disorder are the keys to the diagnosis of PWS.

This case report is the first to describe the detection of antibodies against inositol 1,4,5-trisphosphate receptor 1 (ITPR1, I3PR) in a patient diagnosed with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. ITPR1 is known as one of the Purkinje cell antibodies present in autoimmune cerebellar ataxia (ACA). Here, we described the association between autoimmune GFAP astrocytopathy and autoimmune cerebellar disease (ACD).Demographic features, clinical characteristics, cerebrospinal fluid (CSF) parameters and neuroimaging findings were collected from this patient. Specifically, antibodies against GFAP and other proteins associated with neurological disorders were measured by immunofluorescence staining in both serum and CSF samples.A 52-year-old woman was diagnosed with autoimmune inflammatory meningoencephalitis. She presented with cognitive dysfunction, psychiatric/behavioral abnormalities and serious insomnia with subacute onset. Brain magnetic resonance imaging (MRI) showed bilateral hyperintensity in the semioval centers on axial images and perivascular linear enhancement oriented radially to the ventricles on sagittal images. GFAP-IgG, oligoclonal bands (OBs), N-methyl-D-aspartate receptor (NMDAR)-IgG and ITPR1-IgG co-existed in her CSF. She responded well to immunoglobulin and steroid treatments.Here, we describe the case of a patient with autoimmune GFAP astrocytopathy whose CSF was positive for ITPR1-IgG; however, she did not show typical ataxia manifestations or cerebellar lesions on her MRI scan. This suggests that ITPR1-IgG is not pathogenic, and the positivity of this antibody in CSF is probably associated with the presence of autoimmune inflammation.

Background Little is known about the relationship between ubiquilin 1 (UBQLN1) and p53, both of them have been implicated in the development and progression of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the role of loss of UBQLN1 in cell viability and proliferation, and cell apoptosis in human lung adenocarcinoma A549 cells. Methods Cell viability, proliferation, and apoptosis were determined by MTT, BrdU, and TUNEL assays, respectively. Adenoviruses carrying cDNA or siRNA were used to overexpress or silence target protein. Dihydroethidium (DHE) staining was performed to measure the real-time formation of intracellular reactive oxygen species (ROS). The chymotrypsin-like activity of 20S proteasome core was determined by using synthetic fluorogenic peptide substrate. Results UBQLN1 silencing led to a reduction of p53 protein levels and overexpression of p53 reversed the effects of UBQLN1 knockdown (KD) on cell viability, proliferation, and apoptosis. Furthermore, deficiency of UBQLN1 activated autophagy activity but did not affect proteasome activity. Inhibition of autophagy restored p53 protein levels in UBQLN1-KD A549 cells. In addition, UBQLN1 KD markedly inhibited phosphorylation of mammalian target of rapamycin (mTOR) and its downstream ribosomal S6 kinase (S6K). Conclusions Our experiments suggested that the regulation of UBQLN1 on cell viability, proliferation, and apoptosis was mediated by mTOR/autophagy/p53 signaling pathway.

Young-onset amyotrophic lateral sclerosis (ALS) refers to ALS patients with initial symptoms earlier than 45 years, representing a novel disease pattern. We aim to summarize the clinical and genetic features of 102 young-onset ALS patients in China.

Patients with combined phenotypes of Sturge–Weber syndrome and Klippel–Trenaunay syndrome have been reported, though the underlying genetic spectrum in these individuals remains to be elucidated. We reported the patient presenting with Klippel–Trenaunay and Sturge–Weber overlap syndrome in mainland China. Histopathologic study confirmed the hemangioma of vein and capillary. Co‐existence of a novel somatic KRAS c.182_183 delins TC mutation and GNAQ c.548G>A mutation was identified in the affected skin tissue rather than paired peripheral blood. The somatic mutations of GNAQ and KRAS may affect MAPK‐ERK signaling pathway, resulting in endothelial anomaly and blood vessel malformation.

Background and purpose Amyotrophic lateral sclerosis (ALS)-related genes and mutations have been increasingly discovered recently and an improved understanding of genotype-phenotype relationships may help to predict the disease course and refine genetic diagnosis. Methods We collected clinical data and blood samples from 268 patients and used next-generation sequencing to comprehensively assay genetic variations in a panel of known ALS genes from 2015 to 2019. Results Among these patients, the mean age of onset was 52.30 ± 10.42 years with a mean diagnosis delay of 15.90 ± 11.88 months. Patients with SOD1, TARDBP and FUS variants were more likely to suffer from familial ALS. Additionally, carriers of FUS variants displayed the earliest onset, followed by those with SOD1 variants. Patients with NEFH variants showed a closer link to pesticide exposure. Patients with SETX variants were prone to bulbar onset with moderate anxiety problems. No genotype-phenotype relations were found in SPG11 and ERBB4 mutants. Conclusion Our findings uncovered some genotype-phenotype relationships and may help to predict the disease course of patients with ALS in southern China.

Amyloid-β (Aβ) plaques is one of the typical pathological hallmark of Alzheimer disease (AD). Accumulating evidence suggests that the imbalance between Aβ production and clearance leads to extracellular Aβ accumulation in the brain. It is reported that the blood–brain barrier (BBB) transport plays a predominant role in Aβ clearance from brain to blood. In the present study, we investigated dynamic alterations of BBB transport function in the early disease stage of AD using APPswe/PS1dE9 C57BL/6J (APP/PS1) transgenic mice. Our results showed that the expression of lipoprotein receptor-related protein 1 (LRP-1), a main efflux transporter of BBB, started to decrease at the age of 4 months old. Interestingly, supplementing with fish oil which is rich in omega-3 polyunsaturated fatty acids (PUFAs) significantly enhanced the expression level of LRP-1 and promoted Aβ clearance from the bran to circulation, as revealed by reduced soluble/insoluble Aβ levels and senile plaques in the brain parenchyma and a corresponding increase of Aβ levels in plasma. Besides, fish oil supplement significantly inhibited the NF-κB activation, reduced the expression of interleukin-1β and tumor necrosis factor-α, and suppressed the glial activation in APP/PS1 mice. The results of the study provide evidence that BBB transport function could be impaired at a very early disease stage, which might contribute to Aβ pathological accumulation in AD, and omega-3 PUFAs intervention could be an effective strategy for the prevention of the progression of AD through promoting Aβ clearance from brain-to-blood.

Alcoholism is a risk factor for the development of cognitive decline and dementia. Here we demonstrated that the glymphatic function in the brain was impaired by alcohol administration. Acute moderate alcohol administration substantially retarded and reduced the entry of subarachnoid cerebrospinal fluid (CSF) via the paravascular space into the cerebral parenchyma, thus impaired CSF-interstitial fluid (ISF) exchange and parenchymal amyloid β (Aβ) peptide clearance. The elevated release of β-endorphin and reduced cerebrovascular pulsatility after acute alcohol administration may account for the impairment of the glymphatic function. Chronic moderate alcohol consumption led to pronounced activation of astrocytes and a widespread loss of perivascular AQP4 polarization in the brain, which results in an irreversible impairment of the glymphatic function. The results of the study suggest that impaired glymphatic functions and reduced parenchymal Aβ clearance found in both acute and chronic alcohol treatment may contribute to the development of cognitive decline and dementia in alcoholism.

China is stepping into the aging society. The prevalence of type 2 diabetes among elderly population is increasing in China in the last few decades. However, there is a lack of epidemiological investigations regarding to the aging-related changes of islet function in the elderly population.To investigate the islet function and glycemic conditions in the elderly population of western China.Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a provincial representative sample of 3001 western Chinese elderly adults. A 2 h oral glucose tolerance test (OGTT) was conducted among all study participants, and islet function measurements including HOMA-β, HOMA-IR, HOMA-IS, ΔI30/ΔG30, Ip/I0 were calculated.HOMA-β, HOMA-IR and ΔI30/ΔG30 decreased gradually along with increasing age from age of 55 to age of 80 (p0.05). HOMA-IR, HOMA-β and ΔI30/ΔG30 were significantly higher while HOMA-IS lower among urban residents than rural residents or suburb residents (p0.01). FPG, 2 h plasma glucose (P2hPG) and HbA1C increased with increasing age (p0.05), while fasting insulin level (FINS) and 2 h insulin level (P2hINS) decreased with increasing age (p0.05). FPG, P2hPG and glycated hemoglobin (HbA1C) among suburb residents were lower than among urban residents and among rural residents (p0.05).Islet function decreased gradually along with increasing age with no gender difference among the elderly population in western China. Glycemic outcomes became worse with increasing age. These results indicated that strategies aimed at the prevention of diabetes in the elderly population were needed.

Background: To determine the efficacy and safety of DL-3-n-butylphthalide (NBP) for the treatment of amyotrophic lateral sclerosis (ALS).Methods: A randomized, double-blind, placebo-controlled trial was performed at 19 ALS clinical centers of the Chinese ALS Association. Patients with definite or probable ALS were randomly treated with NBP or placebo for 12 months. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score was the primary endpoint and was evaluated every 3 months. Secondary endpoints included survival and tracheotomy incidence, total Medical Research Council (MRC) score, percentage of predicted forced vital capacity (FVC), and clinical global impression scale score assessed using the visual analog scale. Results: Between November 23, 2015 and November 22, 2017, 312 ALS patients were enrolled and randomly allocated to either the NBP group (156 patients) or placebo group (156 patients). Ninety-three patients in the NBP group and 92 patients in the placebo group were included in the primary end point analysis. There was no significant difference in the ALSFRS-R score, total MRC score, or clinical global impression between the two groups after treatment. The NBP group exhibited a mild trend of less decrease in the percentage of predicted FVC between baseline and the 12-month visit than the placebo group (least-squares mean change from baseline ± standard error: -7.34±4.28, 95％CI(-15.24,0.56), p=0.0335). Adverse events were reported in 56.5% of patients in the placebo group and 68.8% of patients in the NBP group (χ2=2.99, P=0.0838). No serious adverse event related to treatment occurred.Conclusion: we found no evidence that NBP improved the ALSFRS-R score in patients with ALS. The results suggest a mild trend in the percentage of predicted FVC decreased slowly in the NBP treatment group than in the placebo group.Trial registration: A Multi-center, Randomized, Double Blinding, Placebo-Controlled Clinical Trial of Dl-3-Butylphthalide in the Treatment of Amyotrophic Lateral Sclerosis, ChiCTR-IPR-15007365, Registered 1 November 2015, http://www.chictr.org.cn/showproj.aspx?proj=12354

SO2, previously known as the product of industrial waste, has recently been proven to be a novel gasotransmitter in the cardiovascular system. It is endogenously produced from the metabolism pathway of sulfur-containing amino acids in mammalians. Endogenous SO2 acts as an important controller in the regulation of many biological processes including cardiovascular physiological and pathophysiological events. Recently, the studies on the regulatory effect of endogenous SO2 on cell apoptosis and its pathophysiological significance have attracted great attention. Endogenous SO2 can regulate the apoptosis of vascular smooth muscle cells, endothelial cells, cardiomyocytes, neuron, alveolar macrophages, polymorphonuclear neutrophils and retinal photoreceptor cells, which might be involved in the pathogenesis of hypertension, pulmonary hypertension, myocardial injury, brain injury, acute lung injury, and retinal disease. Therefore, in the present study, we described the current findings on how endogenous SO2 is generated and metabolized, and we summarized its regulatory effects on cell apoptosis, underlying mechanisms, and pathophysiological relevance.

SO2, previously known as the product of industrial waste, has recently been proven to be a novel gasotransmitter in the cardiovascular system. It is endogenously produced from the metabolism pathway of sulfur-containing amino acids in mammalians. Endogenous SO2 acts as an important controller in the regulation of many biological processes including cardiovascular physiological and pathophysiological events. Recently, the studies on the regulatory effect of endogenous SO2 on cell apoptosis and its pathophysiological significance have attracted great attention. Endogenous SO2 can regulate the apoptosis of vascular smooth muscle cells, endothelial cells, cardiomyocytes, neuron, alveolar macrophages, polymorphonuclear neutrophils and retinal photoreceptor cells, which might be involved in the pathogenesis of hypertension, pulmonary hypertension, myocardial injury, brain injury, acute lung injury, and retinal disease. Therefore, in the present study, we described the current findings on how endogenous SO2 is generated and metabolized, and we summarized its regulatory effects on cell apoptosis, underlying mechanisms, and pathophysiological relevance.

Asymmetric multicolor displays have unique and fascinating applications in the field of artificial color engineering. However, the realization of such multicolor displays still faces challenges, due to limitations associated with nanofabrication techniques. In this work, asymmetric photonic structures were realized through inclined 2D aluminum nanopillar arrays, which demonstrate asymmetric angle-dependence as multicolor displays. It was numerically and experimentally demonstrated that the distinctive symmetry breaking leads to the plasmonic coupling effect with angle-dependence and reflection differences with the opposite observing angle. Based on this concept, several color printings were designed as prototypes, which prove the utility of the controlled asymmetric color display with varied observing angles. Our results demonstrate a simple and efficient platform for asymmetric plasmonic nanostructures, which paves the way for further study and designation in artificial color engineering.

With the rapid development of economy, informatization has become a trend of global development. Big data is used in public security management, which can manage public security efficiently, prevent related criminal activities effectively, and create an intelligent public security management mode, thus promoting the economic and social development of our country. In view of this, this paper analyzes the relevant connotation of big data, based on the current situation of public security management, analyzes the difficulties encountered by big data in public security management. At the same time, this paper further expounds the influence and function of big data on public security management. Finally, this paper discusses the innovative ideas of big data in public security management from the aspects of innovation consciousness, talent training and data disclosure.

The authors have withdrawn this preprint due to author disagreement.

The glymphatic system plays a central role in the clearance of extracellular wastes from the brain. Cocaine exposure can lead to pathologies that affect the entire brain, resulting in addictive disorders involving motivational and cognitive impairment. However, it remains unknown whether cocaine exposure impairs glymphatic function. In the present study, using a mouse model of noncontingent cocaine exposure, we evaluated glymphatic function including cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and solute clearance during repeated exposures and withdrawal. We found that cocaine treatment, both during repeated exposure and withdrawal, significantly induced widespread astrogliosis and reduced cerebral blood flow (CBF), cerebrovascular pulsatility, and aquaporin-4 (AQP4) polarity. Glymphatic function was greatly impaired in mice after cocaine treatment, as evidenced by reduced CSF influx from paravascular pathways into the brain parenchyma and decreased efflux of interstitial molecules out of the parenchyma. These findings provide evidence that cocaine exposure impairs the clearance of wastes from the brain, which may contribute to the development of neurocognitive disorders in patients with drug addictions.

3D asymmetric structure could induce asymmetric diffraction with spatial coupling behavior for various optical applications, but the study still faces challenges due to the complicated local-field coupling mechanism within structures. In this study, the spatial asymmetry based on inclined all-dielectric structure was theoretically modeled. The normal reflection of the 2D array shows that the increasing structural inclination selectively enhances the Fano resonance between different polarization directions which is mainly due to the oriented spatial coupling effect by increasing structural asymmetry, proved with the near-field distribution. The angular-resolved reflection shows the selected enhancement of first-order diffraction even over that of zero order by combining the structural asymmetry and oblique incidence. Our study provides a new insight for exploring asymmetric photonic structures and relative devices in practical applications.

Background: Our study compares the cosmetic effects, postoperative complications, and quality of life of immediate breast reconstruction with simple prosthesis or prosthesis plus titanium-coated polypropylene mesh (TCPM) after total mastectomy for breast cancer. Methods: In total, 69 patients who underwent total mastectomy, sentinel lymph node biopsy, and immediate prosthetic breast reconstruction from January 2015 to December 2018 in our hospital were selected, and their cosmetic effects, complications, and quality of life after reconstruction were recorded immediately after surgery and 6 months after surgery. Results: Of these 69 patients, 29 were in the simple prosthesis group and 40 in the prosthesis + TCPM group. The incidence of surgical complications was 17.2% in the simple prosthesis group (5/29; including 4 cases of capsular contracture and 1 case of infection) 15.0% in the prosthesis + TCPM group (6/40; 1 case of flap necrosis, 2 cases of poor wound healing, 2 cases of hematomas, and 1 case of inadequate blood supply to nipple). The complications were successfully managed after symptomatic treatment in both groups. No prosthesis loss was noted. The incidence of postoperative complications showed there to be no significant differences between these two groups (P=0.06, χ 2 =0.80). The satisfaction rate of patients on cosmetic effects was 95.0% (38/40) in the prosthesis + TCPM group, significantly higher than that in the simple prosthesis group (75.90%, 22/29) (P=0.05, χ 2 =3.87). The quality of life in the simple prosthesis group at 2 weeks and six months after the operation was significantly lower than that in the prosthesis + TCPM group. The incidence rate of arm pain and fatigue at 2 weeks after operation was significantly higher than that in the prosthesis + TCPM group (P=0.04, χ 2 =4.42). The satisfaction of family life and sexual interest 6 months after the operation was also significantly lower in the simple prosthesis group than in the prosthesis + TCPM group (P=0.03, χ 2 =4.95). Conclusions: Breast reconstruction with prosthesis combined with TCPM does not increase surgical complications and has a good cosmetic effect and high patient satisfaction. Thus, it is a safe and reconstruction method.

Aims This study aimed to understand the characteristics of metabolic syndrome (MetS) in populations (especially females) over 50 years old in Xi’an, China, to avail adjusting prevention strategies in similar regions. Methods 3001 people were included, based on data from “Xi'an Community-Based Management of Diabetes in the Elderly”. The prevalence rate was calculated and analyzed stratifying by gender, age and geography. Results The overall prevalence rates for males and females were 41.9±8.3% and 41.4±11.3% according to 2019 Chinese Diabetes Society diagnosis criteria, 32.0±9.0% and 49.7±9.8% according to International Diabetes Federation diagnosis criteria. The prevalence increased with age in females, but not in males. The prevalence of MetS, as well as abdominal obesity and hypertension, was higher in rural females than in urban and suburban females. Logistic regression analysis showed the risk factors included age, premature menopause, low family income and education level, sedentary time >9 hours/day, weight-gain, and family history of hypertension. Conclusions In Xi'an, China, under the current social-economic conditions, the prevalence of MetS in females over 50 years of age stands higher level than that in males, and the prevalence in rural females is higher than that in urban and suburban females, which deserves more attention.

Immune escape of breast cancer cells contributes to breast cancer pathogenesis. Tumour microenvironment stresses that disrupt protein homeostasis can produce endoplasmic reticulum (ER) stress. The miRNA‐mediated translational repression of mRNAs has been extensively studied in regulating immune escape and ER stress in human cancers. In this study, we identified a novel microRNA (miR)‐27a‐3p and investigated its mechanistic role in promoting immune evasion. The binding affinity between miR‐27a‐3p and MAGI2 was predicted using bioinformatic analysis and verified by dual‐luciferase reporter assay. Ectopic expression and inhibition of miR‐27a‐3p in breast cancer cells were achieved by transduction with mimics and inhibitors. Besides, artificial modulation of MAGI2 and PTEN was done to explore their function in ER stress and immune escape of cancer cells. Of note, exosomes were derived from cancer cells and co‐cultured with macrophages for mechanistic studies. The experimental data suggested that ER stress biomarkers including GRP78, PERK, ATF6, IRE1α and PD‐L1 were overexpressed in breast cancer tissues relative to paracancerous tissues. Endoplasmic reticulum stress promoted exosome secretion and elevated exosomal miR‐27a‐3p expression. Elevation of miR‐27a‐3p and PD‐L1 levels in macrophages was observed in response to exosomes‐overexpressing miR‐27a‐3p in vivo and in vitro. miR‐27a‐3p could target and negatively regulate MAGI2, while MAGI2 down‐regulated PD‐L1 by up‐regulating PTEN to inactivate PI3K/AKT signalling pathway. Less CD4+, CD8+ T cells and IL‐2, and T cells apoptosis were observed in response to co‐culture of macrophages and CD3+ T cells. Conjointly, exosomal miR‐27a‐3p promotes immune evasion by up‐regulating PD‐L1 via MAGI2/PTEN/PI3K axis in breast cancer.

Long noncoding RNAs (lncRNAs) have been certified as important regulators in tumorigenesis. LncRNA GAS6-AS2 (GAS6-AS2) was a newly identified tumor-related lncRNA, and its dysregulation and oncogenic effects in melanoma and bladder cancer had been reported in previous studies. However, the expression pattern and potential function of GAS6-AS2 in osteosarcoma (OS) have not been investigated. In this study, we identified a novel OS-related lncRNA GAS6-AS2. We found that GAS6-AS2 was distinctly upregulated in both OS specimens and cell lines. Distinct up-regulation of GAS6-AS2 in OS was correlated with advanced clinical stages and shorter survivals. In addition, USF1 could directly bind to the GAS6-AS2 promoter and contribute to its overexpression. Furthermore, GAS6-AS2 knockdown caused tumor suppressive effects via reducing cellular proliferation, migration and invasion, and promoting OS cell apoptosis. Besides, GAS6-AS2 directly bound to miR-934 and downregulated its expression. Mechanistically, GAS6-AS2 positively regulated the expression of BCAT1 through sponging miR-934. Taken together, our data illustrated how GAS6-AS2 played an oncogenic role in OS and might offer a potential therapeutic target for treating OS.

Due to the indiscriminate use of chemical inputs like pesticides, serious agricultural diffused pollution is arising, not only with the ecological environment damaging, but also with the agriculture sustainable development restricted. It is imperative for China to reduce pesticides use. Under the decentralized production background, farmers’ willingness to reduce pesticides is worth discussing. This paper aims to explore farmers’ willingness to reduce pesticides use based on its determinants analysis. A structured questionnaire was administered to a random sample of 924 farmers in rural China. Binary logistic regression model was used to examine the determinants. The results showed that farmers’ environmental concern, pesticides residues cognition, agro-products quality concern and input controls positively and significantly influence farmers’ willingness to reduce pesticides, while non-agricultural income share influence negatively. Results also reveal that farmers’ self-discipline is more effective than government regulations; enhancing farmers’ self-discipline is important to guide farmers toward environmentally-friend measures in agricultural production. This paper recommended that policy makers take measures to improve farmers’ environmental awareness and strengthen input supervision. Improved effectiveness of pesticides usage is also needed.

Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure. Our results demonstrated that fish oil significantly reduced the chronic alcohol exposure-induced aberrant dendritic morphologic changes of the medium-sized spiny neurons in the core and the shell of nucleus accumbens. This inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the post synaptic membranes of medium-sized spiny neurons and eventually alleviated withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3 PUFAs are promising for treating withdrawal symptoms and alcohol dependence.

Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia.

Introduction Transoral vestibular endoscopic thyroidectomy (TOET) is sometimes used in young and middle-aged patients with papillary thyroid microcarcinoma (PTMC), but it is still difficult to identify lymph nodes (LNs) and parathyroid glands (PGs). Carbon nanoparticle (CN) is a novel lymph node tracer and has been widely used in open thyroid surgery. Aim To evaluate the efficacy of CN in identifying LNs and preserving PGs in TOET with central neck dissection (CND). Material and methods A total of 72 PTMC patients undergoing TOET with CND were retrospectively enrolled from January 2017 to January 2019. Patients were divided into a CN group (n = 38) and a control group (n = 34). The parameters including pathological characteristics, surgery related indicators, serum Ca2+ and parathyroid hormone (PTH) levels were compared. Results No significant differences were found in patient characteristics, operative complications and superior PGs preserved in situ (all p > 0.05). Total LNs and number of LNs less than 5 mm were significantly higher in the CN group than in the control group (p = 0.021, p < 0.01). The number of superior PGs preserved in situ discovered in the CN group was greater than the control group (p = 0.038). Serum PTH and Ca2+ levels dropped markedly in each group after surgery and gradually recovered in time. The CN group recovered faster than the control group. Conclusions CN may be a good choice for TOET for PTMC because of better protection and faster recovery of parathyroid function, and more LNs removed.

The endoplasmic reticulum (ER)-stress-induced cascade events are implicated in Parkinson’s disease (PD). The discovery of drug candidates to protect dopaminergic (DA) neurons from ER-stress-induced oxidative damage is important to resolve the pathological aspects of PD and modify its progress. In this study, we found that a recently identified unfolded protein response (UPR) modulator, azoramide, showed protective effects on patient induced pluripotent stem cells-derived midbrain DA neurons with the homozygous phospholipase A2 group 6 (PLA2G6) D331Y mutant. A series of PD-related cascade events such as ER stress, abnormal calcium homeostasis, mitochondrial dysfunction, increase of reactive oxygen species, and apoptosis were observed in PLA2G6 D331Y mutant DA neurons, whereas azoramide significantly protected PLA2G6 D331Y mutant DA neurons against these events. The beneficial effects of azoramide were abolished by treatment with a cAMP-response element binding protein (CREB) inhibitor. Our results suggest that azoramide is a potential neuroprotectant against DA neuron damage via restoring ER function and the CREB signaling.

Targeting amyloid-β (Aβ) accumulation seems a promising strategy for the treatment of cerebral amyloid angiopathy (CAA) and neurodegenerative diseases. However, it is still challenging to develop a safe and efficient technology for brain-wide perivascular Aβ clearance. Using intrathecally injected adeno-associated virus 9 (AAV9) encoding soluble form of neprilysin (sNEP), we showed that AAV-sNEP reduced Aβ accumulation and improved cognitive deficits in Tg-SwDI transgenic mice. Meningeal cells, adventitial cells and smooth muscle cells in leptomeningeal arteries and penetrating arterioles were transfected by intrathecal injection of AAV9-sNEP, hence generating sufficient sNEP to exert beneficial effects by perivascular Aβ clearance, protecting against smooth muscle cell damage and pericyte loss, maintaining blood-brain barrier (BBB) integrity, and eventually improving cognitive decline in Tg-SwDI mice. This study provides pre-clinical evidence that intrathecal delivery of AAV-mediated sNEP may be a promising therapeutic strategy for the treatment of CAA. Funding Statement: This study was supported by the Science and Technology Development Fund, Macau SAR (020/2017/A1 and 039/2017/AFJ); multi-year research grant, University of Macau, (MYRG2016-00184-ICMS-QRCM and MYRG2018-00242-ICMS); Science and Technology Program of Guangzhou (No. 2014J4500031) and Guangzhou Clinical Research and Translational Center for Major Neurological Disease (No. 201604020010). Declaration of Interests: The authors declared no conflicts of interest. Ethics Approval Statement: All animal experiments were approved by the ethics committee at the University of Macau (Macau, China) and Sun Yat-Sen University, and performed in compliance with the institutional guidelines.

Nanogap plasmonic structures with strong coupling between separated components have different responses to orthogonal-polarized light, giving rise to giant optical chirality. Here, we proposed a three-dimensional (3D) nanostructure that consists of two vertically and twistedly aligned nanogaps, showing the hybridized charge distribution within 3D structures. It is discovered that the structure twisted by 60° exhibits plasmonic coupling behavior with/without gap modes for different circular-polarized plane waves, showing giant chiral response of 60% at the wavelength of 1550 nm. By controlling the disk radius and the insulator layer, the circular dichroism signal can be further tuned between 1538 and 1626 nm.

The present study aimed to screen potential genes associated with metastatic prostate cancer (PCa), in order to improve the understanding of the mechanisms underlying PCa metastasis. The GSE3325 microarray dataset, which was downloaded from the Gene Expression Omnibus database, consists of seven clinically localized PCa samples, six hormone-refractory metastatic PCa samples and six benign prostate tissue samples. The Linear Models for Microarray Data package was used to identify differentially-expressed genes (DEGs) and a hierarchical cluster analysis for DEGs was performed with the pheatmap package. Furthermore, potential functions for the DEGs were predicted by a functional enrichment analysis. Subsequently, microRNAs (miRNAs) potentially involved in the regulation of PCa metastasis were identified by WebGestalt software, and the miRNA-DEG regulatory network was visualized using Cytoscape. In addition, a pathway enrichment analysis for DEGs in the regulatory network was performed. A total of 306 and 2,073 genes were differentially expressed in the clinically localized PCa and the metastatic PCa groups, respectively, as compared with the benign prostate group, of which 174 were differentially expressed in both groups. A number of the DEGs, including CAMK2D and SH3BP4, were significantly enriched in the cell cycle, and others, such as MAF, were associated with the regulation of cell proliferation. Furthermore, some DEGs (CAMK2D and PCDH17) were observed to be regulated by miR-30, whereas others (ADCY2, MAF, SH3BP4 and PCDH17) were modulated by miR-182. Additionally, ADCY2 and CAMK2D were distinctly enriched in the calcium signaling pathway. The present study identified novel DEGs, including ADCY2, CAMK2D, MAF, SH3BP4 and PCDH17, that may be involved in the metastasis of PCa.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Over 90% of cases are sporadic (sALS) and 5%-10% are familial (fALS). So far, more than 20 genes/loci have been linked to ALS. C9orf72, SOD1, TARDBP, and FUS are noted as the most common ALS genes; however, mutations of these genes explain10% of sALS cases. Recently, Rho guanine nucleotide exchange factor, encoded by ARHGEF28, has been linked to the ALS pathogenesis, possibly by binding low-molecular-weight neurofilament mRNA and affects its stability. However, a systemic screening of ARHGEF28 mutations in ALS is lacking. In this study, we sequenced the entire coding sequence of ARHGEF28 in a Chinese cohort of 399 sporadic ALS and 327 elderly controls. A total of 73 coding variants were identified, including 26 synonymous and 47 nonsynonymous. Among the nonsynonymous variants, 33 were rare (minor allele frequency [MAF]0.01), in which 18 were only identified in cases and 12 were only in controls. Three loss-of-function mutations were identified, including 2 truncations (p.Arg231Ter and p.Ser561Ter) and a frameshift deletion (p.Lys1070fs) in 2 cases and 1 control subject. The frequency of total and case-only rare variants was 7.5% (30/399) and 5.0% (20/399), respectively, in the patients. SKAT-O test suggested that the novel coding variants were marginally enriched in the cases (p = 0.049). Single-variant analysis suggested that the p.Asn1046Ser variant had a higher frequency in cases (8/399, 0.02) than in controls (1/327, 0.003) (OR: 6.67, 95% CI: 0.83-53.61; p = 0.046). By contrast, none of the low-frequency (MAF: 0.01-0.05) or common (MAF0.05) variants was associated with ALS (p0.05). Among all patients, 9 (2.3%) carried rare variants predicted to be deleterious, and the age at onset of these carriers (45.6 ± 10.9 years) was marginally younger than noncarriers (51.9 ± 10.7 years) (p = 0.11). Our results supported a possible genetic contribution of rare but not low-frequency and common coding variants to ALS. These data may have implications in the mechanisms and genetic counseling of the disease.

The B7 family, the most common family of secondary signaling molecules, consists of eight cell-surface proteins, which regulate the T-cell mediated immune response by delivering co-inhibitory or co-stimulatory signals through their corresponding ligands. Among them, natural killer cell cytotoxicity receptor 3 ligand 1 (NCR3LG1, also known as B7H6) has been reported as a new member, and is involved in tumor progression of various types of human cancer. However, the role of B7H6 in triple-negative breast cancer (TNBC) remains unknown. In the present study, western blotting was performed to determine the protein expression levels of B7H6 in a normal mammary epithelial cell line (MCF-10A), non-TNBC breast cancer cell lines (MCF-7 and AU565) and TNBC cell lines (MDA-MB-231 and MDA-MB-468). B7H6 was knocked down using small interfering RNA, and an MTT assay was performed to determine proliferation ability, flow cytometry was used to analyze apoptosis, and Transwell and wound-healing assays were performed to measure migration ability. Expression of proliferation-associated proteins (SMAD family member 4 and β-catenin) and apoptosis-associated proteins (BCL2 associated X, BCL2 apoptosis regulator and caspase-3) were analyzed by western blotting. The results demonstrated that B7H6 was highly expressed in TNBC cells, and that knockdown of B7H6 inhibited cell proliferation and migration, and promoted apoptosis. Furthermore, the results revealed that proliferation and apoptosis-associated proteins were altered in the B7H6-knockdown MDA-MB-231 cells. In conclusion, the present study demonstrated that B7H6 may have significant roles in the regulation of cell proliferation, apoptosis and migration of TNBC cells.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by interactions between environmental factors and genetic susceptibility. Circadian rhythm dysfunction (CRD) is a significant contributor to neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. However, whether CRD contributes to the progression of ALS remains little known. We performed behavioral and physiological tests on SOD1G93A ALS model mice with and without artificially induced CRD, and on wild-type controls; we also analyzed spinal cord samples histologically for differences between groups. We found that CRD accelerated the disease onset and progression of ALS in model mice, as demonstrated by aggravated functional deficits and weight loss, as well as increased motor neuron loss, activated gliosis, and nuclear factor κB-mediated inflammation in the spinal cord. We also found an increasing abundance of enteric cyanobacteria in the ALS model mice shortly after disease onset that was further enhanced by CRD. Our study provides initial evidence on the CRD as a risk factor for ALS, and intestinal cyanobacteria may be involved.

The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) or n-3 fatty acid has been associated with reduced risk of Alzheimer's disease (AD) in epidemiological reports. However, the underlying mechanism remains to be elucidated. Here, we report that exogenous DHA administration could protect neurons against Aβ oligomer-induced injury both in vitro and in vivo, partly through reducing the endoplasmic reticulum (ER) stress, and preventing cell apoptosis. In transgenic fat-1 mice with enriched ω-3 fatty acids, Aβ oligomers induced fewer neuronal losses, when compared to wild-type (WT) mice. We conclude that endogenous DHA are neuroprotective in pathogenesis processes of AD.

The purpose of the present study was to quantify the cumulative randomized evidence for the efficacy and safety of lapatinib combined with neoadjuvant therapy in human epidermal growth factor receptor (HER) 2-positive breast cancer. Three electronic databases, MEDLINE, Embase and Cochrane Central Register of Controlled Trials, and the abstracts of major international conferences between inception and 15 December 2013 were searched. Two evaluators independently extracted data. The end-points assessed consisted of the pathological complete response (pCR) rate, breast-conserving surgery (BCS) rate and the occurrence of adverse events. Four randomized controlled trials were assessed in the present study, involving a total of 779 participants. Compared with the patients who did not receive lapatinib, the pCR rate was higher in the hormone receptor (HR)-positive [risk ratio (RR), 1.39; 95% confidence interval (CI), 1.12–1.72; P=0.002) and HR-negative (RR, 1.38; 95% CI, 1.14–1.68; P=0.0009) patients that received lapatinib. No significant difference between the BCS rate of the two treatment arms was observed in two trials (n=382; RR, 1.14; 95% CI, 0.89–1.47; P=0.31). The primary adverse events, including diarrhea, dermatological toxicity, hepatic toxicity and neutropenia, were statistically more frequent in patients that received lapatinib (RR, 2.46; 95% CI, 1.97–3.07; P

Transient global cerebral ischemia, one of the consequences of cardiac arrest and cardiovascular surgery, usually leads to delayed death of hippocampal cornu Ammonis1 (CA1) neurons and cognitive deficits. Currently, there are no effective preventions or treatments for this condition. Omega-3 (ω-3) PUFAs have been shown to have therapeutic potential in a variety of neurological disorders. Here, we report that the transgenic mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs, were protected from global cerebral ischemia injury. The results of the study show that the hippocampal CA1 neuronal loss and cognitive deficits induced by global ischemia insult were significantly less severe in fat-1 mice than in WT mice controls. The protection against global cerebral ischemia injury was closely correlated with increased production of resolvin D1, suppressed nuclear factor-kappa B activation, and reduced generation of pro-inflammatory mediators in the hippocampus of fat-1 mice compared with WT mice controls. Our study demonstrates that fat-1 mice with high endogenous ω-3 PUFAs exhibit protective effects on hippocampal CA1 neurons and cognitive functions in a global ischemia injury model.

As40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer׳s disease (AD). In the present study, we investigated the possible protective effects of puerarin against As40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. As40 peptides at 5 μM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aβ40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, As40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of As40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10 μM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways.

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

Background: Many breast-imaging techniques have been developed as primary clinical methods for identifying early-stage breast cancers and differentiating them from benign breast tumors. For the large population of China, any screening method that is rapid, economical, and accurate is worthy of evaluation. Objective: To compare the effectiveness of mammography, color Doppler ultrasonography, and far-infrared thermography in the screening and early diagnosis of breast cancer. Methods: Data from 2036 women with breast disease between January 2007 and May 2011 were included in this study. All patients underwent mammography, ultrasonography, and far-infrared thermography imaging. The diagnostic accuracy of the three methods was determined using postoperative pathological results as the diagnostic criterion standard. Results: There were 480 patients found to have breast malignancies on pathological examination. The lesion diameter was Conclusion: Far-infrared thermography is more accurate for breast cancer screening than ultrasonography and mammography for lesions 2 cm in diameter.

// Qi Wu 1,* , Juanjuan Li 1,* , Si Sun 2 , Xiaoli Yao 1 , Shan Zhu 1 , Juan Wu 3 , Qian Liu 1 , Xiaojun Ding 1 , Manman Shi 1 , Kaiyang Li 4 and Shengrong Sun 1 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 2 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 3 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 4 Department of Electronic Science and Technology, School of Physics and Technology, Wuhan University, Wuhan, Hubei, P. R. China * These authors have contributed equally to this work Correspondence to: Shengrong Sun, email: // Keywords : thermal tomography, neoadjuvant chemotherapy, breast cancer Received : December 16, 2016 Accepted : March 15, 2017 Published : March 25, 2017 Abstract Background & Aims: This study aims to analyze the feasibility and predictive value of thermal tomography (TT) for monitoring early treatment response in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC). Methods: Patients with LABC who were due to receive six cycles of NAC were examined by TT prior to NAC, the second cycle of NAC, the fourth cycle of NAC and surgery. Changes in TT parameters and ultrasonography were correlated with pathologic response to NAC, and the predictive value was assessed. Results: Forty-four patients were evaluable for response (25 pathologic responders and 19 nonresponders). As early as after the first cycle of NAC, changes in the TT parameters ΔTs, ΔTn, and ΔTa correlated significantly with pathologic response ( P < 0.05). The best predictor of pathologic response after the 6th cycle of NAC was TT (area under the receiver operating characteristic curve, 0.794), as opposed to cross-sectional areas and the longest diameter by ultrasonography. Conclusions: TT allows for monitoring early tumor response to NAC and can predict pathologic response in the early stages of therapy. Therefore, TT could be used as a novel imaging modality to monitor NAC treatment.

Induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons might be reset back to the fetal state due to reprogramming. Thus, it is a compelling challenge to reliably and efficiently induce disease phenotypes of iPSCs-derived dopaminergic neurons to model late-onset Parkinson’s disease (PD). Here, we applied a small molecule, hydroxyurea (HU), to promote the manifestation of disease relevant phenotypes in iPSCs-based modeling of PD. We established two iPS cell lines derived from two sporadic PD patients. Both patients-iPSCs-derived dopaminergic neurons did not display PD relevant phenotypes after 6 weeks culture. HU treatment remarkably induced ER stress on patients-iPSCs-derived dopaminergic neurons. Moreover, HU treatment significantly reduced neurite outgrowth, decreased the expression of p-AKT and its downstream targets (p-4EBP1 and p-ULK1), and increased the expression level of cleaved-Caspase 3 in patients-iPSCs-derived dopaminergic neurons. The findings of the present study suggest that HU administration could be a convenient and reliable approach to induce disease relevant phenotypes in PD-iPSCs-based models, facilitating to study disease mechanisms and test drug effects.

Induced pluripotent stem cells (iPSCs) exhibit reduced efficiency and higher variability in neural differentiation compared to embryonic stem cells (ESCs). In this study, we showed that mouse iPSCs failed to efficiently give rise to neuronal cells using conventional methods previously established for driving mouse ESC differentiation. We reported a novel approach which remarkably increases neural differentiation of mouse iPSCs. This novel approach initiated embryoid body (EB) formation directly from the whole cell clones isolated from the top of feeder cells. Compared to conventional neural induction methods such as single cell suspension or monolayer culture, the cell clone-derived EB method led to a pronounced increase in directed generation of various types of neural cells including neural stem cells, motoneurons and dopaminergic neurons in response to different inducers. Through gene expression microarray analysis, we identified 14 genes that were highly expressed in the cell clone-derived EBs. Among them, we found that Cdh2, also known as N-cadherin, played important roles in controlling the neural differentiation efficiency of mouse iPSCs. Forced expression of Cdh2 in iPSCs substantially enhanced the differentiation efficiency while knocking-down of Cdh2 by shRNA blocked the neural differentiation. Our results revealed a critical role of Cdh2 in the process of efficient neural differentiation of mouse iPS cells.