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Pine pollen has been widely recognized for its comprehensive nutritional properties and health benefits, but it has also been the target of fraudulent practices. Accurate authentication of pine pollen throughout the production chain is thus of great importance to quality and safety control of pine pollen food products. Aiming at the adverse effects of excipients and DNA degradation during processes, a pretreatment method including dissolution and centrifugation steps was incorporated in DNA extraction, and the chloroplast trnL-F region was used to establish a multiplex species-specific PCR assay. The developed assay could detect 1% of intentional adulteration of cattail pollen or corn flour into pine pollen down to 0.01 ng level of template DNA and was proved to be effective for botanical origin authentication of commercial pine pollen food products. Therefore, the present study provides a simple and sensitive approach for quality control and safety monitoring of commercial pine pollen food products, and the methodology can be applied in botanical origin authenticity control of other pollen products.

To observe the clinical efficacy of long-snake moxibustion plus Western medicine for chronic heart failure due to heart-kidney yang deficiency. A total of 80 patients were randomized into a control group and an observation group, with 40 cases in each group. The control group was treated with routine Western medicine, and the observation group was treated with long-snake moxibustion therapy on the basis of routine Western medicine. Left ventricular ejection fraction (LVEF), stroke volume (SV) and left ventricular end-diastolic diameter (LVEDd) were measured before and after treatment, and the heart function was assessed. The serum brain natriuretic peptide (BNP) level was measured, the 6 min walking distance was recorded, and the Minnesota living with heart failure questionnaire (MLHFQ) was assessed and scored. The serum galectin-3 (Gal-3) and soluble growth stimulation expressed gene 2 (sST2) protein levels were measured. Clinical efficacy was evaluated after treatment. The total effective rate of the observation group was higher than that of the control group, and the difference between the two groups was statistically significant (P

Objective:. This study was to supply information of the Duchenne muscular dystrophy (DMD) mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD/Becker muscular dystrophy genetic counseling and prenatal diagnosis. Methods:. In this retrospective cohort study, three hundred and five pregnancies in 303 pregnant women who has a birth history of DMD/Becker muscular dystrophy patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification followed by Sanger sequencing between January 2014 and December 2018 at Peking Union Medical College Hospital. The mean age of pregnant women was (33.0 ± 4.1) years old. Karyotype analysis was performed to exclude fetal abnormal karyotype. Results:. The detection rate of DMD gene mutation in 303 probands was (296/303) 97.7% with seven families having a negative genetic diagnosis. The mutational spectrum comprised of large arrangements in 288/303 (95.0%) and small mutations in 8/303 (2.6%). Carrier testing was performed among 204 pregnant women among whom, 108 mothers had the same mutation as family proband. Of the 305 pregnancies underwent prenatal diagnosis, 55 of 173 male fetuses were affected. We also performed karyotype analysis and found three abnormal karyotypes of trisomy 21. We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis. We also identified two times of germline mosaicism. Conclusion:. This study demonstrated the distribution and mutation profile of 303 probands and 305 fetuses. Furthermore, considering the possbility of maternl germilne mosaicism, prenatal diagnosis should be suggested to mothers with a proband whether they carry the causative mutation in their blood or not.

Background Zhongyi paste is a traditional Chinese medicine herbal paste that is externally applied to reduce inflammation and relieve pain. Methods An acute foot swelling inflammation model in C57BL/6J mice was established by carrageenan-induced pathogenesis. Zhongyi paste raised the pain threshold and also reduced the degree of swelling in mice with carrageenan-induced foot swelling. Results Analysis indicated that serum tumor necrosis factor-alpha, interleukin-1 beta, and prostaglandin E2 (PGE2) cytokine levels and PGE2 levels in the paw tissue of the mice were decreased by Zhongyi paste treatment. The quantitative polymerase chain reaction and western blot results showed that Zhongyi paste downregulated the mRNA and protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2), and cyclooxygenase-2 (COX-2), and also downregulated the mRNA expression of PGE2. At the same time, the Zhongyi paste exerted a stronger effect as an external drug than that of indomethacin, which is an oral drug, and voltaren, which is an externally applied drug. Conclusions Our results indicated that Zhongyi paste is a very effective drug to reduce inflammatory swelling of the foot, and its mechanism of action is related to regulation of the ERK1/2-COX-2-PGE2 pathway.

Heterogeneity in either chemically or microbiologically induced carbonate-based ground improvement methods is a major obstacle in engineering application. Spectral induced polarization (SIP), an innovative and nondestructive method, which has demonstrated promise in monitoring microbial activity, was used in this study to monitor enzyme induced carbonate precipitation (EICP). The complex conductivities, together with the shear wave velocities (Vs), of an EICP modified sand were monitored using a self-developed spectral induced polarization–bender element column. The mean precipitate size was calculated by relaxation time (τ) and the Schwarz equation. The precipitate contents were calculated by cumulative gamma distribution function on the global polarization magnitude (mn) with R2 = 0.989. The stiffness of the enhanced geomaterial, in terms of Vs, correlates to mn with a cumulative lognormal distribution function with R2 = 0.967. Contact cementation was postulated as the dominant association pattern. The possible mechanism for this may be the formation of eddies and the nucleation of CaCO3 crystals during precipitation. The results suggest that SIP can be used as an effective nondestructive monitoring tool to assess the stiffness of geomaterials.

Calreticulin (CALR) is a multifunctional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding, and cancer progression. However, the role of CALR in breast cancer (BC) is unclear. Here, we report that CALR is overexpressed in BC compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24−CD44+ cells, and aldehyde dehydrogenase–expressing cells, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation and metastasis and enhanced chemosensitivity in vivo. Chromatin immunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic BC cells. CALR expression was correlated with Wnt/β-catenin pathway activation, and an activator of Wnt/β-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALR facilitates BC progression by promoting the BCSC phenotype through Wnt/β-catenin signaling in an HIF-1–dependent manner and suggest that CALR may represent a target for BC therapy.

Cancer remains one of the top culprits causing disease-related deaths. A lack of effective multi-cancer therapeutic targets has limited the prolongation of cancer patients’ survival. Therefore, it is important to explore novel oncogenic genes or versatile targets and perform a comprehensive analysis to assess their roles in the process of tumorigenesis. OSBPL3 protein is an intracellular lipid receptor of the oxysterol-binding protein superfamily, which participates in some pathological and physiological processes in tumor progression. However, its clinical roles and potential mechanisms in cancers remain unknown. Thus, we aimed to systematic explore the potential oncogenic roles of OSBPL3 across thirty-three tumors using multiple web-based and publicly available tools, including the Cancer Genome Atlas, Gene Expression Omnibus, Genotype-Tissue Expression, cBioPortal, and Human Protein Atlas database. OSBPL3 is highly expressed in major subtypes of cancers, distinctly associated with the prognosis of tumor patients. We observed X676_splice/V676G alteration in the oxysterol domain and frequent mutations of OSBPL3 involve cell survival in skin cutaneous melanoma. We also first presented that the expression of OSBPL3 was associated with tumor mutational burden (TMB) in nine cancer types. Additionally, OSBPL3 shows an enhanced phosphorylation level at S426, S251, and S273 loci within the pleckstrin homology domain in multiple tumors, such as breast cancer or lung adenocarcinoma. And OSBPL3 expression was associated with active immune cells (CD8+ T cells) and cancer-associated fibroblasts in breast cancer, colon adenocarcinoma, and kidney renal clear cell carcinoma and immune checkpoint genes in more than 30 tumors, but weakly associated with immune suppressive cells (myeloid-derived suppressor cells, T regulatory cells). Moreover, protein processing and mRNA metabolic signaling pathways were involved in the functional mechanisms of OSBPL3. Our study first demonstrated that a novel agent OSBPL3 plays an important role in tumorigenesis from the perspective of publicly available databases and clinical tumor samples in various cancers, which comprehensively provide insights into its biological functions and may be helpful for further investigation.

Background Frequent injection of high-dose methylprednisolone (MP) is used to treat spinal cord injury (SCI), but free MP is associated with various side effects and its water solubility is low, limiting potential dosing regimes and administration routes. Albumin-based nanoparticles, which can encapsulate therapeutic drugs and release cargo in a controlled pattern, show high biocompatibility and low toxicity. The Nogo protein, expressed on the surface of oligodendrocytes, can inhibit axonal growth by binding with the axonal Nogo receptor (NgR). Peptide NEP1-40, an NgR antagonist, can bind specifically to Nogo, significantly improving functional recovery and axon growth in the corticospinal tract. Therefore, we hypothesized that delivering MP within nanoparticles decorated with NEP1-40 could avoid the disadvantages of free MP and enhance its therapeutic efficacy against SCI. Results We used human serum albumin to prepare MP-loaded NPs (MP-NPs), to whose surface we conjugated NEP1-40 to form NEP1-40-MP-NPs. Transmission electron microscopy indicated successful formation of nanoparticles. NEP1-40-MP-NPs were taken up significantly better than MP-NPs by the Nogo-positive cell line RSC-96 and were associated with significantly higher Basso–Beattie–Bresnahan locomotor scores in rats recovering from SCI. Micro-computed tomography assay showed that NEP1-40-MP-NPs mitigated SCI-associated loss of bone mineral density and accelerated spinal cord repair. Conclusions NEP1-40-MP-NPs can enhance the therapeutic effects of MP against SCI. This novel platform may also be useful for delivering other types of drugs. Electronic supplementary material The online version of this article (10.1186/s12951-019-0449-3) contains supplementary material, which is available to authorized users.

Objective To investigate the factors associated with cell-free DNA test failure, and the optimal subsequent management of these pregnancies. Methods This was a retrospective study of 27,363 singleton pregnancies undergoing cell-free DNA testing. Women with cell-free DNA test failure were divided into a high-risk group and a low-risk group according to their indications. The subsequent management and pregnancy outcomes of these women were followed up. Results The rate of cell-free DNA test failure at the first sampling was 1.49%, and 78.4% of failures were due to a low fetal fraction. Of the 66 women who refused any subsequent management, an adverse pregnancy outcome was seen in 5 cases, all belonging to the high-risk group. Of the 13 low-risk women who chose second-trimester maternal serum screening, all obtained a low-risk maternal serum screening result and an unaffected pregnancy outcome. A redraw was chosen by 171 women, which yielded a result in 75.4% and their pregnancy outcomes were unaffected; 42 women had an uninformative result again and received an amniocentesis. As 158 women had an amniocentesis after the first sampling, this procedure was offered in 200 cases altogether. Abnormal genetic testing results were shown in six (3%, 6/200) cases, all in the high-risk group. Conclusions High-risk pregnant women with cell-free DNA test failure are at increased risk of adverse pregnancy outcomes. A second sampling for cell-free DNA test or maternal serum screening might be suggested to low-risk women. Invasive prenatal diagnosis should be offered to the high-risk patients, especially those with a second cell-free DNA test failure.

Objectives: To investigate the risk factors for shoulder pain after stroke, and prevent its occurrence effectively. Methods: The patients with stroke treated in our hospital between September 2016 and October 2020 were reviewed retrospectively. The medical records of the included patients including age, gender, lesion side, stroke duration, hospital stay, diabetes, hypertension, heart disease, limitation of shoulder joint activity, alcohol abuse, smoking, type of stroke, Ashworth scale, Brunnstrom stage, sensory disorders, and motor arm score of National Institutes of Health Stroke Scale (NIHSS) were collected and analyzed to determine the risk factors for shoulder pain after stroke. Results: A total of 1390 patients were included based on the inclusion and exclusion criteria, consisting of 162 patients with shoulder pain after stroke and the prevalence was 11.6%. The included patients were divided into shoulder pain group and non-shoulder pain group. There were significant differences in age, stroke duration, hospital stay, diabetes, limitation of shoulder joint activity, Ashworth scale, Brunnstrom stage, sensory disorders, and motor arm score of NIHSS between the two groups (P < 0.05). Based on the multivariate regression analysis, the independent risk factors for shoulder pain after stroke included diabetes, limited shoulder joint activity, Brunnstrom grade I-III period, Ashworth 3-4 grade, motor arm score of NIHSS 3-4 points, and sensory disturbance. Conclusion: Great emphasis should be placed on the stroke patients with diabetes, limited shoulder joint activity, Brunnstrom grade I-III period, Ashworth 3-4 grade, motor arm score of NIHSS 3-4 points, or sensory disturbance, as these patients have higher risks for shoulder pain after stroke. doi: https://doi.org/10.12669/pjms.38.1.4594 How to cite this:Hao N, Zhang M, Li Y, Guo Y. Risk factors for shoulder pain after stroke: A clinical study. Pak J Med Sci. 2022;38(1):145-149. doi: https://doi.org/10.12669/pjms.38.1.4594 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6&ndash, 8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2&ndash, 3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester.

Bin Wang,* Siyuan Jiang,* Lizhe Zhu, Wei Sheng, Yan Qiao, Huimin Zhang, Jian Zhang, Yang Liu, Na Hao, Xiaoxia Ma, Can Zhou, Yu Ren Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Can Zhou; Yu RenDepartment of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi, People’s Republic of ChinaTel +86 13700222161Email zhoucanz2005@126.com ; renyyyyy@126.comIntroduction: Nipple discharge is a common symptom of breast disease. We aimed to perform a descriptive statistical analysis of the cases we evaluated and establish a model to predict intraductal tumors.Materials and Methods: We conducted a retrospective study of patients from 2007 to 2019. In total, 1333 patients who completed the fiberoptic ductoscopy (FDS) were evaluated. The variables were analyzed by χ2 test. Logistic regression was used to analyze the relationship between the patient’s clinical characteristics and intraductal tumors and establish a predictive model. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of the predictive ability of the model. Calibration curves and decision curve analysis (DCA) were used to evaluate the model.Results: Patients with spontaneous, single-duct, bloody discharge and a smooth ductal wall were more likely to be diagnosed with tumors by ductoscopy. A model was established based on five variables: age, side of discharge, spontaneous discharge status, duration of discharge, and color of discharge. The model was subsequently validated in 183 patients with complete data on the variables in the validation cohort. The area under the ROC curve (AUC) was calculated to be 0.716, indicating good predictive ability.Conclusion: Patients with the clinical characteristics of unilateral, bloody, single-duct, spontaneous discharge and a smooth ductal wall were more likely to have intraductal tumors by ductoscopy. Our nomogram can effectively predict intraductal tumors in patients with nipple discharge.Keywords: nipple discharge, ductoscopy, nomogram, breast tumor

Soil and groundwater contamination with lead (Pb) poses serious challenges for the environment. Activated carbon (AC) and biochar have huge potential application in the in-situ remediation processes through permeable reactive barriers (PRB). Spectral induced polarization (SIP) technique recently showed promises in nondestructively monitoring the spatio-temporal characteristics of physical, chemical and biological processes in porous media. In this study SIP technique was used for monitoring Pb remediation by AC and biochar in column scale. The calculated characteristic grain/pore size evolutions from SIP signals on AC, agreed well with the size of precipitates measured by SEM and mercury intrusion porosimetry (MIP) methods. The content increment process of the retained Pb on AC was also recorded via the magnitude increment of the imaginary conductivity. The mechanisms of Pb-AC and Pb-biochar interactions were investigated using SEM-EDS, TEM, FTIR, XRD, and XPS measurements. It showed that AC immobilizes through physical adsorption and precipitation, whereas complexation with functional groups is the remediation mechanism for biochar. Furthermore, the observed SIP responses of both AC and biochar are two orders of magnitude higher than those of typical natural soils or silica materials. This distinct difference is an additional advantage for the field application of SIP technique in PRB scenarios.

Background: Duchenne muscular dystrophy (DMD) has showed a wide spectrum of mutations in the dystrophin gene including exon deletions, duplications and small mutations. This retrospective study was to supply information of the DMD mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD genetic counselling and prenatal diagnosis.Methods: In this retrospective study, 305 pregnancies in 303 pregnant women who has a birth history of DMD patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification (MLPA) followed by Sanger sequencing between 2014 and 2018. Karyotype analysis was performed to exclude fetal abnormal karyotype.Results: The detection rate of DMD gene mutation in 303 probands was 97.7% with 7 families having a negative genetic diagnosis. The mutational spectrum comprised of large arrangements in 288/303 (95.0%) and small mutations in 8/303 (2.6%). 204 pregnant women did carrier testing among whom, 108 mothers had the same mutation as family proband. Of the 305 pregnancies underwent prenatal diagnosis, 55 of 173 male fetuses were affected. We also performed karyotype analysis and found 3 abnormal karyotypes of trisomy 21. We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis.Conclusions: The distribution and mutation profile of 303 probands and 305 fetuses were demonstrated. Given the large samples provided in this study, the information is essential for genetic counselling and prenatal diagnosis in DMD families in China.

Percutaneous ethanol injection (PEI) therapy was used in liver cancer treatment, however, the therapeutic ethanol in PEI easily flew away from injected solid tumours and hinder the treatment effect. In this paper, injectable supramolecular gels formed by self-assembly of low molecular weight gelators (LMWGs) based on glycylglycine modified phenylboronic acid were prepared to localize ethanol and load chemotherapeutic drug for in situ synergistic therapy. The mechanism, morphology and rheological property of supramolecular gels were characterized by NMR, UV, SEM, etc. The rheological study revealed that the gels were formed in situ rapidly and recovered promptly once damaged. The gels were non-toxicity to both normal 3T3 fibroblasts cells and 4T1 breast cancer cells. Doxorubicin (DOX) hydrochloride and ethanol were encapsulated in the gels for the combination of chemotherapy and PEI therapy. The in vivo anticancer activity of the DOX-loaded gels was carried out in tumour bearing mice. The injected gels were coated around tumour tissues to lock ethanol, and DOX was released sustainingly from the gels to maintain effective concentration to induce the apoptosis of tumour cells. DOX-loaded gels and the ethanol exhibited excellent therapeutic efficacy and low side effects in local cancer therapy.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Long-term, high-dose glucocorticoid therapy can be used to treat the disease, but the fact that the drug distributes systemically can give rise to severe adverse effects. Here we develop a targeted system for treating RA in which the glucocorticoid prednisolone (PD) is encapsulated within solid lipid nanoparticles (SLNs) coated with hyaluronic acid (HA), giving rise to HA-SLNs/PD. HA binds to hyaluronic receptor CD44, which is over-expressed on the surface of synovial lymphocytes, macrophages and fibroblasts in inflamed joints in RA. As predicted, HA-SLNs/PD particles accumulated in affected joint tissue after intravenous injection into mice with collagen-induced arthritis (CIA), and HA-SLNs/PD persisted longer in circulation and preserved bone and cartilage better than free drug or drug encapsulated in SLNs without HA. HA-SLNs/PD reduced joint swelling, bone erosion and levels of inflammatory cytokines in serum. These results suggest that encapsulating glucocorticoids such as PD in HA-coated SLNs may render them safe and effective for treating inflammatory disorders.

Liver cancer is a fatal disease with limited therapy options. The recombinant adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective antitumor activity against liver cancer. However, its disadvantages produced great limitation on its application, especially its nonspecific and toxicity to normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over-expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially target to EpCAM-positive cells. Based on this founding, we aimed to design a kind of gene delivery system of EpDT3-mediated Ad5-PTEN (EpDT3-PEG-Ad5-PTEN, EPAP) in which polyethylene glycol was used to be a linker to conjugate EpDT3 with Ad5-PTEN. This strategy may overcome the disadvantages of naked Ad5-PTEN and enhance the antitumor effect on liver cancer. The SDS-PAGE electrophoresis, TBE-PAGE electrophoresis and fluorescence detection were conducted to confirm the successful preparation of EPAP. Compared with the naked Ad5-PTEN, EPAP showed significant anti-proliferative and anti-migratory activities against HepG2 cells. EPAP also showed selective and precise target ability to EpCAM-positive HepG2 cells in vivo. Therefore, EPAP may be further explored as a novel effective anticancer drug for malignant liver cancer.

To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down’s syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down’s syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down’s syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down’s syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down’s syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a “before and after” two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation.Impact statementChildren born with Down’s syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down’s syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down’s syndrome and to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down’s syndrome. Results demonstrate that fetal cfDNA can significantly reduce false-positive rate close to none while distinguishing all true positives. Thus, we recommend that fetal cfDNA analysis to be utilized as a secondary screening tool atop of the primary blood protein screening to further minimize the capacity of undesirable invasive diagnostic operations.

In order to avoid the instability and quick separation between emulsifier and drug in the interventional chemoembolization, an injectable low molecular weight peptide gel (LMWG) was prepared to localize ethanol and chemotherapeutic for in situ synergistic therapy. The formation mechanism, rheological property and morphology of the LMWG were investigated by NMR, UV-vis, MS and SEM. The interaction between gelator and anticancer drug doxorubicin hydrochloride (DOX) was evaluated by fluorescence spectroscopy and its contribution on drug loading properties was demonstrated. The gel was non-toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. DOX as well as ethanol were encapsulated in the gel and injected in breast cancer bearing mice with low drug dose (2.5 mg/kg body weight). The LMWG surrounded tumors act as a depot for ethanol release and release DOX to induce the apoptosis of cancer cells. With the combination of percutaneous ethanol injection (PEI) and chemotherapy, the DOX loaded LMWG exhibited great significance in necrosis of tumor tissue and exciting tumor inhibition efficiency.

It is a significant challenge to develop nanoscale magnetic resonance imaging (MRI) contrast agents with high performance of relaxation. In this work, Gd3+-doped CaF2-based core–shell nanoparticles (CaF2:Yb,Er@CaF2:Gd) of sub-10 nm size were controllably synthesized by a facile sequential growth method. The as-prepared hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles modified using PEG-PAA di-block copolymer benefited from the presence of Gd only in the outer CaF2 layer of the nanoparticles, which exhibited r1 as high as 21.86 mM−1 s−1 under 3.0 T, seven times as high as that of commercially used gadopentetate dimeglumine (Gd-DTPA). Low cytotoxicity, no hemolysis phenomenon and no potential gadolinium ion leakage phenomenon of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles have been observed and confirmed. Clear vascular details can be observed in magnetic resonance angiography and obvious MR signal of 4T1 tumor area could be significantly improved by intravenous injection of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles at a low dosage in mice. A series of in vivo biological safety evaluations confirmed the good biocompatibility of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles, which might be employed in clinical blood pool imaging and tumor diagnosis as a safe and efficient MRI probe.

As the implications of reactive oxygen species (ROS) are elucidated in many diseases, ROS-responsive nanoparticles are attracting great interest from researchers. In this work, a ROS sensitive thioketal (TK) moiety with a π-conjugated structure was introduced into biodegradable methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)mPEG-TK-PCL micelles as a linker, which was designed to speed up the drug release and thus enhance the therapeutic efficacy. The micelle showed a high drug loading content of 12.8% and excellent stability under physiological conditions because of the evocation of π-π stacking and hydrophobic interactions with the anticancer drug doxorubicin (DOX). The polymeric micelle presented a better drug carrier capacity and higher in vitro anticancer efficacy towards cancer cells. The in vivo study showed that DOX-loaded mPEG-TK-PCL micelles displayed lower toxicity towards normal cells and remarkably enhanced antitumor efficacy. This research provides a way to design potential drug carriers for efficient cancer chemotherapy.

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity in vivo and in vivo than DOX-loaded micelles made from the commonly used material mPEG-PCL. Under laser irradiation, the photosensitizing protoporphyrin of DOX/PTPP produces abundant reactive oxygen species (ROS) that directly kill tumor cells as well as destroy the micelles themselves, leading to drug release. The ROS and DOX then act synergistically against the tumors. These ROS-responsive, laser-sensitive polymeric micelles may be useful for combining PDT and chemotherapy.

Background In this study, we investigated the association of time-varying serum albumin levels with mortality over a 5-year period in one cohort of patients undergoing long-term peritoneal dialysis (PD) therapy. Methods The participants in this study enrolled 302 patients who underwent long-term PD at a single PD center in Taiwan. We reviewed medical records from 2011 to 2015 retrospectively. Time-averaged albumin level and serum albumin reach rate (defined as the percentage of serum albumin measurements that reached ≥3.5 g/dL) were applied as the predictor variables in the first 2 years (2011–2012). All-cause mortality was used as the outcome variable in the subsequent 3 years (2013–2015). Hazard function of all-cause mortality in the study participants was examined by using Cox proportional hazard regression models . Results Patients with different albumin reach rates (75–

Background/Aims: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. Methods: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. Results: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44–1.82 in HFHD, 0.79–1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. Conclusion: Hospitalization rates and AAC were observed to be equal for HDF and HFHD.

Patients on peritoneal dialysis (PD) encounter peritoneal functional and structural alterations. It is still unknown whether levels of plasminogen activator inhibitor type 1 (PAI-1), matrix metalloproteinases- (MMP-) 2, and vascular endothelial growth factor (VEGF) exhibit dynamic changes in peritoneal effluents. The aim of the present study was to investigate the longitudinal changes in these biomarkers in PD patients and their association with peritoneal small-solute transfer rate (PSTR). This prospective, single-center cohort study included 70 new PD patients. The presence of PAI-1, MMP-2, and VEGF in peritoneal effluents was measured regularly after PD initiation. The association between those biomarkers and 4-hour effluent:plasma creatinine ratio (PSTR) was analyzed. Longitudinal follow-up showed a tendency for PAI-1 (p< 0.001) and VEGF (p= 0.04) to increase with the duration of PD. Both PSTR at baseline and PSTR at 2 years significantly associated with PAI-1, MMP-2, and VEGF levels at baseline. PSTR at 2 years also associated with the MMP-2 level at 6 months and PAI-1 level at baseline. The present study illustrated a positive association of PSTR with selected biomarkers in peritoneal effluents observed over a 2-year period.

Purpose To evaluate the diagnostic efficacy of virtual touch tissue quantification (VTQ) and contrast-enhanced ultrasonography (CEUS), separately and in combination, in diagnosing malignant focal liver lesions (FLLs). Methods Forty-six patients with 55 FLLs (28 benign and 27 malignant) underwent both VTQ and CEUS. The diagnostic values of VTQ and CEUS, alone and in combination, were compared. Results The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of CEUS were 92.6% (25/27), 96.4% (27/28), 94.5% (52/55), 96.2% (25/26), and 93.1% (27/29), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ with a cutoff of 2.22 m/s were 51.9% (14/27), 85.7% (24/28), 69.1% (38/55), 77.8% (14/18), and 64.9% (24/37), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ and CEUS combined were 96.3% (26/27), 82.1% (23/28), 89.1% (49/55), 83.9% (26/31), and 95.8% (23/24), respectively. Comparing the accuracies of the three methods, the diagnostic values of CEUS and of the combination of CEUS with VTQ were significantly higher than those of VTQ alone (p ≤ 0.01). There was no significant difference between the combination of CEUS with VTQ and CEUS (p = 0.49). Conclusions CEUS is superior to VTQ in diagnosing malignant FLLs. Adding VTQ to CEUS did not improve the diagnosis of FLLs. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound, 2016

The gel dosimeter has the unique capacity in recording radiation dose distribution in three dimensions (3D), which has the specific advantages in dosimetry measurements where steep dose gradients exist, such as in intensity-modulated radiation therapy (IMRT), brachytherapy and so on. Some 3D dosimeters, such as Fricke gel dosimeters, polymer gel dosimeters, the PRESAGE plastic dosimeters and micelle gel dosimeters have appeared recently. However, there are several disadvantages of these 3D dosimeters limit their application in radiotherapy dose verification. In this study, a novel radiochromic gel dosimeter for 3D dose verification of radiotherapy was developed by dispersing nanovesicles self-assembled by 10,12-pentacosadiynoic acid (PCDA) into the tissue equivalence gel matrix. The characteristics of radiochromic PCDA vesicle gel dosimeters were evaluated. The results indicate that these radiochromic gel dosimeters have good linear dose response to X-ray irradiation in the dose range of 2–100 Gy. In addition, the radiochromic gel dosimeters breakthrough the limitations of the existing gel dosimeters such as diffusion effect, post-radiation effect, and poor forming ability. The response of the gel dosimeter does not show any dose rate dependence, energy dependence and temperature effect, and there was no obvious difference in the gel response between single and cumulative dose of fractional irradiation. Hence, the radiochromic PCDA vesicle gel dosimeters developed in this study could be generally applied to 3D dose verification in radiotherapy.

Statins, known for their lipid-lowering effects, also have immunomodulatory properties. This study aims to examine whether systematic simvastatin administration could decrease polymorphonuclear neutrophils (PMNs) infiltration into brain tissue, as well as alleviate neuroinflammation in a rat model of intracerebral hemorrhage (ICH). The ICH model was induced in adult male Sprague–Dawley rats by an injection of autologous blood. Animals randomly received simvastatin (i.p. 2 mg/kg) or vehicle daily from 5 days before ICH until sacrificed. Routine blood counts, brain water content, neurological scoring, immunofluorescence and RT-PCR were conducted to evaluate the anti-inflammatory effect of simvastatin following ICH. Furthermore, flow cytometric and western blotting analysis were implemented for elucidating the mechanisms involved in simvastatin-induced reduction of neutrophil brain-invading. Elevated PMNs count and neutrophil-to-lymphocyte ratio in circulation were detected in rat model of ICH, which was reversed by using simvastatin. Simvastatin effectively alleviated PMNs infiltration and proinflammatory factors release in perihematomal area, as well as attenuated ICH-induced brain edema and neurological deficits. Simvastatin significantly downregulated the expression of antiapoptotic protein-Mcl-1 while increased the level of proapoptotic protein-Bax and cleaved caspase 3 in PMNs. Simvastatin treatment significantly alleviated PMNs brain-infiltrating and subsequent neuroinflammatory reaction after ICH, in part by accelerating peripheral PMNs apoptosis through disorganized the expression of apoptotic related proteins. Our data provided new evidence for simvastatin application on patients with ICH.

Considerable evidence suggests that as breast cancer progresses, genetic and epigenetic mechanisms contribute to the emergence of self-renewing cells (CSC), which may also arise as a consequence of metastasis. Although the molecular pathways that trigger stemness and metastasis are known, key molecular and mechanistic gaps in our understanding of these processes remain unclear. Here, we first screened the inflammation-associated stemness gene phosphodiesterase 3A (PDE3A) using a medium-throughput siRNA library, which was overexpressed in breast tumors and significantly correlated with clinical progression. PDE3A induced the inflammatory nuclear factor NFκB signaling pathway by suppressing cAMP/PKA, which promotes the expression of the stem cell marker OCT4. In addition, PDE3A also promoted the translocation of CCDC88A from the cytoplasm to nuclei, thereby boosting the invasion–metastasis cascade in breast cancer. Most importantly, the PDE3A-selective inhibitor cilostazol dramatically suppressed breast tumor growth and reduced metastasis to the lungs in xenograft breast cancer models, with minimum toxicity. Taken together, we show that PDE3A could predispose patients with breast cancer to metastases by acting as a mediator of cancer stemness. PDE3A is a potential therapeutic target for advanced breast cancer.

The aim of the present study was to investigate the combination of certain serological markers (Forns’ index; FI), FibroScan® and acoustic radiation force impulse elastography (ARFI) in the assessment of liver fibrosis in patients with hepatitis B, and to explore the impact of inflammatory activity and steatosis on the accuracy of these diagnostic methods. Eighty-one patients who had been diagnosed with hepatitis B were recruited and the stage of fibrosis was determined by biopsy. The diagnostic accuracy of FI, FibroScan and ARFI, as well as that of the combination of these methods, was evaluated based on the conformity of the results from these tests with those of biopsies. The effect of concomitant inflammation on diagnostic accuracy was also investigated by dividing the patients into two groups based on the grade of inflammation (G

The targeted delivery of a photosensitizer (PS) with appropriate carriers represents an attractive means of selectively delivering cargo to target tissues or subcellular compartments for photodynamic therapy (PDT). Herein, a three-arm distyryl BODIPY derivative conjugated with mannose units (denoted by BTM) that can co-assemble with Tween 80 to form nanomicelles (BTM-NMs) for targeted PDT is reported. MDA-MB-231 breast cancer cells recognized and specifically internalized BTM-NMs via mannose-receptor-mediated endocytosis with preferential accumulation in the lysosomes. These NMs could disassemble in cell lysosomes and subsequently induce highly efficient singlet oxygen (1O2) generation upon light irradiation. 1O2 disrupted the lysosomal membrane and promoted the escape of BTM from the lysosome into the cytoplasm, thereby resulting in the efficient and selective killing of cancer cells through PDT. This study may provide a new strategy for designing targeted PDT systems to fight cancer.

Metal-organic frameworks as a powerful platform for drug delivery have attracted significant attention in recent years. In this study, mesoporous iron-metal-organic framework nanoparticles (mesoMOFs) were synthesized via the double-template method. Cetyltrimethylammonium bromide (CTAB) and citric acid (CA) were chosen as the double-template agent. The mesoMOFs were characterized by EDX, elemental analysis, TG, BET, SEM, TEM, and DLS. The anticancer drug doxorubicin hydrochloride (DOX) was encapsulated in the mesoMOFs, and the DOX loading content was up to 55 wt%. The mesoMOFs are non-toxic to both 4T1 breast cancer cells and 3T3 fibroblasts. The DOX-loaded mesoMOFs exhibit a better anti-tumor effect than free doxorubicin in vitro. The in vivo anticancer activities of the DOX-loaded mesoMOFs were investigated in 4T1 breast cancer-bearing mice. The intratumoral injection of DOX-loaded mesoMOFs revealed that the mesoMOFs could significantly reduce the systemic toxicity of DOX, sustainably release DOX, and maintain an effective DOX concentration for chemotherapy. The DOX-loaded mesoMOFs exhibit excellent therapeutic efficacy and low side effects in local chemotherapy.

We compared two contrast agents, agitated saline and agitated saline with blood, with respect to their efficacy in the diagnosis of right-to-left shunt with contrast-enhanced transcranial Doppler. Three hundred thirty Chinese patients underwent examinations with one of four different methods in random order: (i) 9 mL agitated saline solution with 1 mL air without the Valsalva maneuver (ASwoVM); (ii) 9 mL agitated saline solution with 1 mL air with the Valsalva maneuver (ASwVM); (iii) 9 mL agitated saline solution, 1 mL air and a drop of the patient's blood without the Valsalva maneuver (ASbwoVM); and (iv) 9 mL agitated saline solution, 1 mL air and a drop of the patient's blood, with the Valsalva maneuver (ASbwVM). Rates of detection were 11.5%, 17.9%, 16.7% and 23.6% for the ASwoVM, ASwVM, ASbwoVM, and ASbwVM examinations, respectively. The embolus track numbers for these examinations were 4.0 ± 1.83, 11.5 ± 6.2, 10.5 ± 4.9 and 33.7 ± 14.9, respectively. There were significant differences between the four groups (all comparisons, p < 0.001). For contrast-enhanced transcranial Doppler examinations, the agitated saline/blood agent yielded better rates of diagnosis of right to-left shunt than did the agitated saline alone.

Endometriosis is a common multifactorial disease caused by an interaction between multiple gene loci and environment. Four genome-wide association studies (GWASs) of endometriosis have identified several single-nucleotide polymorphisms (SNPs) associated with endometriosis. However, results from independent replication studies with different populations are inconsistent. The present study aims to evaluate whether the GWAS-derived susceptibility loci are correlated with the risk of the development of ovarian endometriosis in North Chinese women. This case-control study comprised 580 patients with ovarian endometriosis and 606 matched control women. Three SNPs were selected for this association study including rs10965235 in CDKN2BAS, rs2235529 located in LI NC00339-WNT4, and rs 12700667 in an intergenic region on 7p 15.2. The results show that the G/A genotype of rs 12700667 can significantly increase the risk of developing ovarian endometriosis when compared with the G/G genotype (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.23–2.00). Similarly, the carriers with A allele showed a higher risk of ovarian endometriosis than those with G allele (OR = 1.23, 95% CI = 1.12–1.68). The study suggests that the endometriosis-associated genetic polymorphisms (rs 12700667) from GWAS be associated with the risk of developing ovarian endometriosis in North Chinese women.

Field measurements of dynamic characteristics of the multi-storey reinforced concrete frame structure buildings were carried out, by using the ambient vibration test technique, and structural modal parameters were extracted. The measured results and calculated results in accordance with current design specifications were compared. Results show that for multi-storey reinforced concrete frame structure, the measured vibration period of structure is close to the natural period calculated in accordance with the empirical formula of the “Load Code for the Design of Building Structures”. In the actual project, when the designer calculate the natural period if considering only the quality of the infill walls, without considering the stiffness of the infill walls, the period should be shortened. In this paper, the recommended period shortening factor for the multi-storey reinforced concrete frame structure is gave 0.4~0.5.

1. Hydrogen sulphide (H₂S), one of three signalling gasotransmitters, plays an important role in oxidative stress and apoptosis. However, the effects of H₂S on oxidative stress-induced apoptosis in focal cerebral ischaemic injury in rats have not been clarified. 2. In the present study, sodium hydrosulphide (NaHS) was used as the H₂S donor. Eighty-four Sprague-Dawley rats were randomly divided into six groups: sham, sham + low-dose (2.8 mg/kg) NaHS, sham + high-dose (11.2 mg/kg) NaHS, infarct, infarct + low-dose NaHS and infarct + high-dose NaHS. The focal cerebral ischaemic model was created by cranially inserting a nylon thread with a rounded tip into an internal carotid artery. Rats were killed 21 h after administration of NaHS. 3. In the infarct + low-dose NaHS compared with infarct group, infarct volume was significantly decreased and injury to the mitochondria in nerve cells was mitigated. Furthermore, significant increases were seen in mitochondrial superoxide dismutase and glutathione peroxidase activity and neuronal bcl-2 protein levels, whereas mitochondrial malondialdehyde content and neuronal bax and caspase 3 protein levels were significantly decreased, in the infarct + low-dose NaHS compared with infarct group. The effects seen in the infarct group were significantly aggravated in the infarct + high-dose NaHS group. 4. The findings of the present study provide novel evidence for the dual effects of H₂S on focal cerebral ischaemic injury via modulation of oxidative stress-induced apoptosis.

The KINGFISH project (Key Insights on Nearby Galaxies: a Far-Infrared Survey with Herschel) is an imaging and spectroscopic survey of 61 nearby (d < 30 Mpc) galaxies, chosen to cover a wide range of galaxy properties and local interstellar medium (ISM) environments found in the nearby Universe. Its broad goals are to characterize the ISM of present-day galaxies, the heating and cooling of their gaseous and dust components, and to better understand the physical processes linking star formation and the ISM. KINGFISH is a direct descendant of the Spitzer Infrared Nearby Galaxies Survey (SINGS), which produced complete Spitzer imaging and spectroscopic mapping and a comprehensive set of multi-wavelength ancillary observations for the sample. The Herschel imaging consists of complete maps for the galaxies at 70, 100, 160, 250, 350, and 500 microns. The spectal line imaging of the principal atomic ISM cooling lines ([OI]63um, [OIII]88um, [NII]122,205um, and [CII]158um) covers the subregions in the centers and disks that already have been mapped in the mid-infrared with Spitzer. The KINGFISH and SINGS multi-wavelength datasets combined provide panchromatic mapping of the galaxies sufficient to resolve individual star-forming regions, and tracing the important heating and cooling channels of the ISM, across a wide range of local extragalactic ISM environments. This paper summarizes the scientific strategy for KINGFISH, the properties of the galaxy sample, the observing strategy, and data processing and products. It also presents a combined Spitzer and Herschel image atlas for the KINGFISH galaxies, covering the wavelength range 3.6 -- 500 microns. All imaging and spectroscopy data products will be released to the Herschel user generated product archives.

Heparin is an effective competitive antagonist of inositol 1,4,5-trisphosphate receptors (IP(3)Rs). It binds to IP(3)Rs and affects calcium homeostasis. Ultra-low-molecular-weight heparin (ULMWH) is heparin's derivative, the present study was designed to test the effects of ULMWH on intracellular calcium concentration ([Ca(2+)]i) in primary cultured neurons. [Ca(2+)]i was measured by Multilabel Counter Victor-1420 using Fura-2/AM as the calcium fluorescent probe. The results indicated that ULMWH decreased the resting [Ca(2+)]i with or without extracellular Ca(2+). They had no effects on high K(+)-induced elevation of intracellular Ca(2+) level indicating that ULMWH had no effect on external Ca(2+) influx mediated by voltage-dependent calcium channels. However, they partially reduced the increase in [Ca(2+)]i induced by glutamate. Furthermore, ULMWH significantly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)]i both in cellular and subcellular level. These results suggest that ULMWH may reduce [Ca(2+)]i in neurons through suppressing Ca(2+) release from IP(3)-sensitive stores.

Objective To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea. Methods G banding was done for 340 patients with primary amenorrhea to facilitate individual chromosome identification, and if specific staining for certain portions of the chromosome was necessary, C banding was used. The clinical data were recorded by physical examination and ultrasound scanning. Results Karyotype analysis of the 340 patients revealed that 180 (52.94%) patients had normal female karyotypes and 160 (47.06%) patients had abnormal karyotypes. The abnormal karyotypes included abnormal X chromosome (150 patients), mosaic X-Y chromosome (4 patients), abnormal autosome (5 patients), and X-autosome translocation (1 patient). The main clinical manifestations in patients with primary amenorrhea were primordial or absent uterus (95.9%), invisible secondary sex features (68.8%), little or absent ovary (62.6%), and short stature (30.0%). The incidence of short stature in patients with X chromosome aberration (46%, 69/150) was significangly higher that in patients with 46, XX (9.44%, 17/180) as well as 46, XY (6.67%, 3/45; χ2=146.25, P=0.000). All primary amenorrhea patients with deletion or break-point at Xp11.1-11.4 were short statures. Conclusions One of the main reasons of primary amenorrhea is choromosome abnormality, especially heterosome abnormality. It implies the need to routinely screen chromosomal anomalies for such patients. There might be relationship between Xp11.1-11.4 integrity and height improvement.

Low-molecular-weight heparin (LMWH) and ultra-low-molecular-weight heparin (ULMWH) are heparin's derivatives, having various pharmacological effects. The present study aims to investigate the effect of ULMWH on amyloid β peptide (Aβ25–35)-induced neurotoxicity in cultured rat cortical neurons, and LMWH was employed as a positive control agent. The neurons were incubated with Aβ25–35 (35 μM), Aβ25–35 plus ULMWH (2, 10, 50 μg/ml) or LMWH (10 μg/ml) for 24 h. The cell viability was assessed by MTT and LDH release. FITC-Annexin V/PI double staining, Hoechst 33258 staining, TUNEL and Western blotting for bcl-2 and caspase-3 were employed to measure the neuron apoptosis. Furthermore, the intracellular Ca 2+ concentration was measured by a fluorescent dye, Fura-2/AM. The results showed that ULMWH significantly increased cell viability and the protein expression levels of bcl-2 and decreased the LDH release, the number of apoptotic cells, the concentration of intracellular Ca 2+ and the protein expression levels of caspase-3 in cortical neurons, suggesting that ULMWH can obviously reduce Aβ25–35-induced neurotoxic effects and might act as a potential agent for Alzheimer's disease.