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Background The prevalence of Fabry disease (FD) in Chinese patients with hypertrophic cardiomyopathy (HCM) is unclear. We aimed to evaluate the prevalence, clinical characteristics, and outcomes of FD in Chinese patients with HCM. Methods Of 217 patients with HCM, FD probands were screened by next-generation sequencing at Fuwai Hospital. Medical data from α-galactosidase A activity, electrocardiography, echocardiography, coronary angiography, cardiac magnetic resonance, pathological examination, and follow up was analyzed. Results Two FD probands were observed (0.93% of patients with HCM), both of which were diagnosed with symptomatic obstructive HCM at 49 years of age. One proband had a GLA mutation (c.887T>C [p.M296T]) with a late-onset cardiac variant, which was characterized by dual ventricular hypertrophy and conduction disease with a permanent pacemaker. The other patient had a GLA mutation (c.758T>C [p.I253T]) with a classic phenotype and dual ventricular hypertrophy, atrioventricular block, renal failure, and recurrent cerebral infarction. Both probands had late gadolinium enhancement mainly in the basal segment of the inferolateral wall. Follow up revealed no exertional symptoms or outflow obstruction after surgical septal myectomy in the two probands, and stable renal function was observed after 6 months of migalastat therapy in the later one. A family study revealed six female carriers and three sudden cardiac deaths. Conclusions FD is not uncommon in Chinese patients with HCM. Multiple organic involvement, dual ventricular hypertrophy, and conduction disease provide clinical clues for suspected FD, and early genetic screening is necessary. Surgical septal myectomy and migalastat improve the long-term prognosis of patients with FD.

Cell polarity is an intrinsic property of epithelial cells regulated by scaffold proteins. The CRB (crumbs) complex is known to play a predominant role in the dynamic cooperative network of polarity scaffold proteins. PATJ (PALS1-associated tight junction) is the core component in the CRB complex and has been highly conserved throughout evolution. PATJ is crucial to several important events in organisms’ survival, including embryonic development, cell polarity, and barrier establishment. A recent study shows that PATJ plays an important role in functional outcomes of stroke. In this article, we elaborate on the biological structure and physiological functions of PATJ and explore the underlying mechanisms of PATJ genetic polymorphism that are associated with poor functional outcomes in ischemic stroke.

Hepatocytes are the main cell components of the liver and perform metabolic, detoxification, and endocrine functions. Functional hepatocytes are of great value in drug development, toxicity evaluation, and cell therapy for liver diseases. In recent years, an increasing number of in vitro models have been developed to screen drugs and test their toxicity. However, maintaining hepatocyte function in vitro for a long time is a serious challenge. Even freshly isolated liver cells cultured for a short time may lose function via spontaneous dedifferentiation. Thus, novel cell culture systems allowing extended hepatocyte maintenance and more predictive long-term in vitro studies are required. In this study, we developed a conditioned culture system composed of a small-molecule combination that can maintain hepatocyte morphology and functions over the long term. Two-month culture of primary human hepatocytes showed that the conditioned medium was able to stably preserve hepatic functions such as albumin and α-antitrypsin secretion, hepatic transport activity, urea synthesis, and ammonia elimination. Furthermore, this culture model can be used to assess drug-induced hepatotoxicity in vitro. In summary, our work suggests a feasible approach to maintain hepatocyte function in vitro and proposes a promising model for long-term toxicological studies and drug development.

In both normal turnover of the hepatic tissue and acute hepatic injury, the liver predominantly activates terminally differentiated hepatocytes to proliferate and repair. However, in chronic and severe chronic injury, this capacity fails, and liver progenitor cells (LPCs) can give rise to hepatocytes to restore both hepatic architecture and liver metabolic function. Although the promotion of LPC-to-hepatocyte differentiation to acquire a considerable number of functional hepatocytes could serve as a potentially new therapeutic option for patients with end-stage liver disease, its development first requires the identification of the molecular mechanisms driving this process. Here, we found that the epithelial cell adhesion molecule (EpCAM), a progenitor cell marker, regulates the differentiation of LPCs into hepatocytes through Notch1 signaling pathway. Western blotting (WB) revealed a consistent expression pattern of EpCAM and Notch1 during LPC-to-hepatocyte differentiation in vitro. Additionally, overexpression of EpCAM blocked LPC-to-hepatocyte differentiation, which was in consistent with the repressive role of Notch signaling during hepatic differentiation. WB and immunofluorescence data also showed that the upregulation of EpCAM expression increased the generation of Notch intracellular domain (N1ICD), indicating the promotion of Notch1 activity. Our results established the EpCAM-Notch1 signaling axis as an inhibitory mechanism preventing LPC-to-hepatocyte differentiation in vitro.

Supplemental material, sj-pdf-5-wso-10.1177_17474930221140792 for Human blood metabolites and lacunar stroke: A Mendelian randomization study by Meng-Nan Guo, Xiao-Yan Hao, Jie Tian, Yun-Chao Wang, Jia-Di Li, Yu Fan, Jing-Jing Shi, Dong-Rui Ma, Shuang-Jie Li, Chun-Yan Zuo, Yuan-Yuan Liang, Meng-Jie Li, Si Shen, Fen Liu, Da-Bao Yao, Yu-Ming Xu and Chang-He Shi in International Journal of Stroke

Supplemental material, sj-pdf-2-wso-10.1177_17474930221140792 for Human blood metabolites and lacunar stroke: A Mendelian randomization study by Meng-Nan Guo, Xiao-Yan Hao, Jie Tian, Yun-Chao Wang, Jia-Di Li, Yu Fan, Jing-Jing Shi, Dong-Rui Ma, Shuang-Jie Li, Chun-Yan Zuo, Yuan-Yuan Liang, Meng-Jie Li, Si Shen, Fen Liu, Da-Bao Yao, Yu-Ming Xu and Chang-He Shi in International Journal of Stroke

Supplemental material, sj-pdf-1-wso-10.1177_17474930221140792 for Human blood metabolites and lacunar stroke: A Mendelian randomization study by Meng-Nan Guo, Xiao-Yan Hao, Jie Tian, Yun-Chao Wang, Jia-Di Li, Yu Fan, Jing-Jing Shi, Dong-Rui Ma, Shuang-Jie Li, Chun-Yan Zuo, Yuan-Yuan Liang, Meng-Jie Li, Si Shen, Fen Liu, Da-Bao Yao, Yu-Ming Xu and Chang-He Shi in International Journal of Stroke

Supplemental material, sj-pdf-3-wso-10.1177_17474930221140792 for Human blood metabolites and lacunar stroke: A Mendelian randomization study by Meng-Nan Guo, Xiao-Yan Hao, Jie Tian, Yun-Chao Wang, Jia-Di Li, Yu Fan, Jing-Jing Shi, Dong-Rui Ma, Shuang-Jie Li, Chun-Yan Zuo, Yuan-Yuan Liang, Meng-Jie Li, Si Shen, Fen Liu, Da-Bao Yao, Yu-Ming Xu and Chang-He Shi in International Journal of Stroke

Supplemental material, sj-pdf-4-wso-10.1177_17474930221140792 for Human blood metabolites and lacunar stroke: A Mendelian randomization study by Meng-Nan Guo, Xiao-Yan Hao, Jie Tian, Yun-Chao Wang, Jia-Di Li, Yu Fan, Jing-Jing Shi, Dong-Rui Ma, Shuang-Jie Li, Chun-Yan Zuo, Yuan-Yuan Liang, Meng-Jie Li, Si Shen, Fen Liu, Da-Bao Yao, Yu-Ming Xu and Chang-He Shi in International Journal of Stroke

Quantitative evaluation and driving mechanism analysis of vegetation dynamics are essential for promoting regional sustainable development. In the past 20 years, the ecological environment in Altay Prefecture has changed significantly due to global warming. Meanwhile, with increasing human activities, the spatiotemporal pattern and driving forces of vegetation variation in the area are uncertain and difficult to accurately assess. Hence, we quantified the vegetation growth by using the Normalized Difference Vegetation Index (NDVI) on the Google Earth Engine (GEE). Then, the spatiotemporal patterns of vegetation from 2000 to 2019 were analyzed at the pixel scale. Finally, significance threshold segmentation was performed using meteorological data based on the correlation analysis results, and the contributions of climate change and human activities to vegetation variation were quantified. The results demonstrated that the vegetation coverage in Altay Prefecture is mainly concentrated in the north. The vegetation areas representing significant restoration and degradation from 2000 to 2019 accounted for 24.08% and 1.24% of Altay Prefecture, respectively. Moreover, spatial correlation analysis showed that the areas with significant correlations between NDVI and temperature, precipitation and sunlight hours accounted for 3.3%, 6.9% and 20.3% of Altay Prefecture, respectively. In the significant restoration area, 18.94% was dominated by multiple factors, while 3.4% was dominated by human activities, and 1.74% was dominated by climate change. Within the significant degradation area, abnormal degradation and climate change controlled 1.07% and 0.17%, respectively. This study revealed the dynamic changes of vegetation and their driving mechanisms in Altay Prefecture, and can provide scientific support for further research on life community mechanism theory and key remediation technology of mountain-water-forest-farmland-lake-grass in Altay Prefecture.

Rationale: The idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver injury and a key challenge in late-stage drug development. Individual heterogeneity is considered to be an essential factor of iDILI. However, few in vitro model can predict heterogeneity in iDILI. We have previously shown that mouse and human hepatocytes can be converted to expandable liver progenitor-like cells in vitro (HepLPCs). However, the limited proliferation potential of human HepLPCs confines its industrial application. Here, we reported the generation of a novel hepatocyte model not only to provide unlimited cell sources for human hepatocytes but also to establish a tool for studying iDILI in vitro. Methods: Human primary hepatocytes were isolated by modified two-step perfusion technique. The chemical reprogramming culture condition together with gene-transfer were then used to generate the immortalized HepLPC cell lines (iHepLPCs). Growth curve, doubling time, and karyotype were analyzed to evaluate the proliferation characteristics of iHepLPCs. Modified Hepatocyte Maturation Medium and 3D spheroid culture were applied to re-differentiate iHepLPCs. Results: iHepLPCs exhibited efficient expansion for at least 40 population doublings, with a stable proliferative ability. They could easily differentiate back into metabolically functional hepatocytes in vitro within 10 days. Furthermore, under three-dimensional culture conditions, the formed hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes. Importantly, we established a hepatocyte bank by generating a specific number of such cell lines. Screening for population heterogeneity allowed us to analyze the in vitro heterogeneous responses to hepatotoxicity induced by molecular targeted drugs. Conclusions: In light of the proliferative capacity and the heterogeneity they represented, these iHepLPCs cell lines may offer assistance in studying xenobiotic metabolism as well as liver diseases in vitro.

The modern categories of endogenous non-coding RNAs, namely circular RNAs (circRNAs), involved within the carcinogenesis and progression of various human cancers. The fundamental aim of the current investigation was the evaluation of the hsa_circ_0014130 expressions, their biological functions, and potential regulatory network in bladder cancer. The level of expression for hsa_circ_0014130 was evaluated by qRT-PCR, and its relationships to clinicopathological features and survival outcomes of cases experiencing cancer of the bladder were scrutinized. The impact of hsa_circ_0014130 expressions on biological attitudes of bladder cancer cells in vitro was investigated. The interactions between hsa_circ_0014130 and microRNA (miRNA) sponge, miRNA, and its direct targets were determined by RNA pull-down as well as luciferase reporter gene assay. The correlations of their expression were determined by Pearson's correlation analysis. Rescue experiments were carried out to identify the biological roles of the regulation network. The expressions of hsa_circ_0014130 were markedly ameliorated in bladder cancer samples and linked with aggressive characteristics and unfavorable survival. Ectopic expression of hsa_circ_0014130 clearly enhanced the differentiation, proliferative, migratory, invasive potential of the cell in bladder cancer, and the development of tumor xenograft in vivo, while malignant biological behaviors were inhibited by hsa_circ_0014130 knockdown. The expression of hsa_circ_0014130 was tied to miR-132-3p in a negative manner with the cells and tissues of bladder cancer. hsa_circ_0014130 function as a competitive endogenous RNA for miR-132-3p to play oncogenic roles in bladder cancer cells. On the other hand, KCNJ12 was a straightforward target of miR-132-3p at the downstream, and the expressions of KCNJ12 were inversely related to that of miR-132-3p. Furthermore, a significantly positive correlation was found between hsa_circ_0014130 and KCNJ12 mRNA expression. More importantly, the oncogenic impact of hsa_circ_0014130 on bladder cancer cells was partly suppressed by ectopic expression of miR-132-3p or KCNJ12 knockdown. The underlined data revealed that hsa_circ_0014130 exerted its biological roles by regulating miR-132-3p/KCNJ12 expression. Further research revealed hsa_circ_0014130/miR-132-3p/KCNJ12 axis has participated in the Epithelial-mesenchymal transition (EMT) progress and GSK3β/AKT signaling pathway. hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulation of the KCNJ12 expression. These achievements might ameliorate the comprehension of tumor pathogenesis and provide novel therapeutic targets for cancer of the bladder.

OBJECTIVES To investigate the procedure success rate and clinical outcomes of in-stent restenotic chronic total occlusion (ISR-CTO) percutaneous coronary intervention (PCI). BACKGROUND Few studies have reported the short- and long-term clinical outcomes of ISR-CTO PCI. METHOD Patients who underwent ISR-CTO (n = 212) or de-novo CTO (n = 2,447) PCI at Fuwai Hospital from 2010 to 2013 were enrolled. Thirty-day and 5-year clinical outcomes were analyzed. The primary outcome was the incidence of all-cause death, myocardial infarction (MI), and heart failure at follow-up. The secondary outcome was the recanalization result (reasonable, suboptimal, or failed recanalization). RESULTS ISR-CTO PCI had a higher rate of suboptimal recanalization than de-novo CTO PCI (p

Septicemia of grass carp is a systemic inflammatory reaction caused by bacterial infection. More and more evidences show that long non-coding RNAs (lncRNAs) can participate in the regulation of inflammatory response. In the present study, lncRNA-WAS and lncRNA-C8807 were confirmed to be involved in the inflammatory response following infection with Aeromonas hydrophila. LncRNA-WAS and lncRNA-C8807 could interact with miR-142a-3p. LncRNA-WAS and lncRNA-C8807 interact with miR-142a-3p to effect pro-inflammatory genes and NF-κB pathway. Our results provide a theoretical basis for studying the molecular mechanism underlying the regulation of inflammation by lncRNA in grass carp.

Background Cumulative evidence from several tumor studies, including bladder cancer, emphasizes the importance of the tumor microenvironment (TME) in tumorigenesis, development, and metastasis, which can be regulated by long non-coding RNAs (lncRNAs). This study aims to identify bladder cancer (BC) microenvironment-associated lncRNAs for their prognostic value predicting the survival of BC patients. Methods The data of BC patients regarding lncRNA expression and corresponding clinical characteristics were obtained from The Cancer Genome Atlas (TCGA). The Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis were performed to screen lncRNAs following the calculation of the immune score for each sample. For the screened lncRNAs, a risk score model was constructed to predict the survival, and 3- and 5-year overall survival (OS) rates were assessed using a nomogram. The calibration curve and concordance index (C-index) validated the performance of the nomogram. Finally, to explore the potential function related to the screened lncRNAs, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Results The multivariate Cox regression analysis screened five TME-associated lncRNAs regarded as independent factors influencing the tumor progression. The corresponding risk score model was established as follows: (-0.15816 AC064805.1) + (0.10015 AC084033.3) + (-0.17977 AC092112.1) + (-0.05673AC103691.1) + (0.17789 AL391704.1) + (-0.16258 LINC00892). The C-index for the nomogram was 0.63 (95% CI: 0.625-0.635). Also, the calibration curve verified the predictive effectiveness by showing a good concordance between the nomogram prediction and the actual observation. GO and KEGG analysis demonstrated that six TME-associated lncRNAs were most likely linked to tumor metastasis and progression. Conclusion The present study determined six lncRNAs as independent immuno-biomarkers in the TME, constructed a nomogram to predict their prognostic value, and investigated the potential biological processes to understand their regulatory roles in the progression of BC.

Clinical advancement of the bioartificial liver is hampered by the lack of expandable human hepatocytes and appropriate bioreactors and carriers to encourage hepatic cells to function during extracorporeal circulation. We have recently developed an efficient approach for derivation of expandable liver progenitor-like cells from human primary hepatocytes (HepLPCs). Here, we generated immortalized and functionally enhanced HepLPCs by introducing FOXA3, a hepatocyte nuclear factor that enables potentially complete hepatic function. When cultured on macroporous carriers in an air-liquid interactive bioartificial liver (Ali-BAL) support device, the integrated cells were alternately exposed to aeration and nutrition and grew to form high-density three-dimensional constructs. This led to highly efficient mass transfer and supported liver functions such as albumin biosynthesis and ammonia detoxification via ureagenesis. In a porcine model of drug overdose-induced acute liver failure (ALF), extracorporeal Ali-BAL treatment for 3 hours prevented hepatic encephalopathy and led to markedly improved survival (83%, n = 6) compared to ALF control (17%, n = 6, P = 0.02) and device-only (no-cell) therapy (0%, n = 6, P = 0.003). The blood ammonia concentrations, as well as the biochemical and coagulation indices, were reduced in Ali-BAL-treated pigs. Ali-BAL treatment attenuated liver damage, ameliorated inflammation, and enhanced liver regeneration in the ALF porcine model and could be considered as a potential therapeutic avenue for patients with ALF.

T-cell lymphoma (TCL) is a group of heterogeneous disorders with a poor response to conventional treatment. In order to identify novel therapeutic targets, the present study investigated the effect of leptin and its receptor on glucose metabolism in TCL. The expression of the leptin receptor (ObR), and glucose transporter (Glut)1 and 4 was detected in TCL and reactive lymphoid hyperplasia (RLH) tissues by immunohistochemical analysis. A higher level of ObR expression was observed in the TCL tissues than in the RLH tissues (58.3 vs. 22.2%; P=0.012), and ObR overexpression was associated with high expression of Glut1 (P=0.007). In vitro analysis using the human TCL MOLT-3 cell line demonstrated that leptin stimulated cell glucose uptake via promoting recruitment and expression of Glut1, effects which were abolished by ObR-specific small interfering RNA (siRNA). Additionally, MOLT-3 cell viability was also increased following leptin treatment. ObR-specific siRNA abolished these responses. In conclusion, these results suggested that leptin serves a critical role in TCL glucose uptake via the ObR.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for secondary stroke prevention in stroke patients with preexisting cardiovascular diseases (CVD) or cerebrovascular diseases (CeVD). However, data on attainment of guideline-recommended LDL-C levels are lacking. METHODS: We analyzed data from the Chinese Stroke Center Alliance (CSCA) program for patients with ischemic stroke and transient ischemic attack (TIA) hospitalized between August 2015 and July 2019. Participants were classified into different disease groups according to preexisting CeVD (stroke/TIA) or CVD [coronary heart disease (CHD) or myocardial infarction (MI)]. RESULTS: Of 858,509 patients presenting with an acute stroke/TIA, 251,176 (29.3%) had a preexisting CeVD, 44,158 (5.1%) had preexisting CVD, 33,070 (3.9%) had concomitant preexisting CeVD and CVD, and 530,105 (61.7%) had no documented history of CeVD/CVD. Overall, only 397,596 (46.3%) met the target for LDL-C

Summary: During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders. : Qin et al. find that CDYL plays a role in neuronal migration by repressing RhoA transcription. CDYL deficiency leads to increased excitability of cortical pyramidal neurons and susceptibility to epilepsy in mice. Keywords: CDYL, neuronal migration, transcription, RhoA, epilepsy

Four distinctive but poorly documented landforms in the Badain Jaran megadunes were studied: arcuate steps, multi-stage fans, depressions formed by runoff erosion, and groundwater overflow zones around lakes. The development of these four landform types indicates the following: (1) The hydrological balance in the sand layers of the megadune areas is positive, (2) After evaporation and transpiration, precipitation is able to infiltrate the deep sand layers, (3) Precipitation is a source for the groundwater and for many of the lakes of the area. The groundwater recharge mechanism is characterized by intense precipitation events that provide a water source, high infiltration rate, shallow evaporation depth, and low water retention. These factors together enable the precipitation to be transformed into groundwater. The energy of gravity water and the high water film pressure of adsorbed water together provide the forces necessary for effective water recharge.

The most essential tools for studying drug hepatotoxicity, liver diseases, and bioartificial livers have always been models that can recapitulate liver physiology in vitro. The liver progenitor cell line HepaRG represents an effective surrogate of the primary hepatocyte. However, the differentiation of HepaRG relies on long-term induction using a high concentration of dimethyl sulfoxide (DMSO), which may compromise the research of drug metabolism and restrict the applicability of this hepatic model. Here, we present a novel hepatic maturation medium (HMM) for the differentiation of HepaRG, which is based on a cocktail of soluble molecules that mimick the in vivo environment. We showed that HMM could rapidly (about nine days) induce HepaRG differentiation into polarized hepatocytes with maturely metabolic functions. In addition, under three-dimensional culture conditions, the hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes (PHH). Our work demonstrates the utility of HMM as an alternative to the DMSO-dependent differentiation protocol for HepaRG; moreover, these results facilitate the application of HepaRG.

Background Breast cancer is one of the most lethal cancers in women when it reaches the metastatic stage. The plant Carpesium cernuum has been used as an anti-inflammatory, analgesic, and detoxifying agent in Chinese folk medicine. However, the inhibitory activity and molecular mechanisms of Carpesium cernuum in breast cancer cells have not been investigated. Methods RNA sequencing experiments were performed to elucidate the cellular pathways affected by Carpesium cernuum extract (CCE). Cell viability and EdU incorporation assays were conducted to determine the effect of CCE on cell proliferation. The inhibitory effects of CCE on the expression levels of target genes were confirmed by qRT-PCR and Western blot. Cell migration and invasion were analysed with transwell chamber assays. Results Proliferation assays indicated that CCE inhibited cell proliferation in multiple cancer cell lines and the IC50 value of CCE was the smallest in MDA-MB-231 cells. Transcriptome analysis showed that CCE significantly affected the cell adhesion pathway. Further experiments revealed that CCE suppressed cell migration and invasion. The inhibitory effect on migration was likely mediated by targeting TIMP1, MMP9, CD44 and COL4A2. The main active components of CCE were isolated, and CCE-derived sesquiterpene lactone substances could reproduce the inhibitory effect of CCE on cell migration and invasion. Conclusions Overall, both molecular and phenotypic assays showed that CCE has potential in the treatment of breast cancer, especially for the treatment of breast cancer metastasis. CCE-derived sesquiterpene lactone substances are the foundation for the tumor inhibitory effect of CCE.

Backgrounds: Tumor regression grade (TRG) reflects the chemoradiosensitivity of rectal cancer patients undergone neoadjuvant treatment, and relates to distinct probabilities of cancer recurrence and survival. However, in clinical practice, it is significantly challenging to rely solely on radiographic or clinical diagnostic information to obtain a patient's pathological response pre-treatment for treatment optimization. The aim was combining both the tumor information of macroscopic radiological and microscopic pathological images to develop and validated a more accurate signature for pretreatment prediction of TRG to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) on a multicenter dataset. Materials and Methods: We prospectively enrolled 981 patients (303 in the primary cohort, 678 in three external validation cohort) with clinicopathologically confirmed LARC treated with nCRT followed by surgery between Aug 2007 and Nov 2017, and collected their pretreatment multi-parametric MRI (mp-MRI), whole-slide image (WSI) of biopsy specimen, and pathologic response according to AJCC TRG system as well as clinical outcomes. Briefly, an artificial intelligence model integrating quantitative imaging features of mp-MRI and WSI was proposed to predict each nCRT treated patient into a particular 4-category TRG. The signature from the model (hereafter Rp-Grade) was further assessed in three independent validation cohort. Results: Rp-Grade yielded an overall ACC of 87.76% and revealed significant improvement than signature generating from model with mp-MRI or WSI features alone in all validation cohorts (P Performance of radiopathomics signature for predicting 4-category AJCC/CAP TRGMetrics (%) [95% CI]Validation Cohort1 (N=480)Validation Cohort2 (N=150)Validation Cohort3 (N=48)Accuracy87.76 [84.86-90.66]79.71 [72.52-84.9]81.24 [70.15-92.34]PPV (TRG=0)94.58 [90.48-98.69]93.52 [84.68-100.0]83.09 [61.19-100.0]PPV (TRG=1)92.02 [86.19-97.85]70.26 [56.42-84.1]70.26 [56.42-84.1]PPV (TRG=2)83.9 [79.6-88.19]74.24 [63.57-84.92]71.49 [52.04-90.94]PPV (TRG=3)-92.54 [78.21-100.0]-Sensitivity (TRG=0)96.49 [93.03-99.95]96.62 [89.92-100.0]91.3 [74.73-100.0]Sensitivity (TRG=1)96.49 [93.03-99.95]75.57 [61.75-89.4]63.39 [42.96-83.82]Sensitivity (TRG=2)97.16 [95.02-99.29]100.0 [100.0-100.0]100.0 [100.0 100.0]Sensitivity (TRG=3)-35.55 [19.99-51.12]-Note: The evaluation results were represented by ‘-' when the number of categories was insufficient in the independent cohort test. Conclusions: Combining the macroscopic radiological information of the whole tumor and microscopic pathological information of local lesions from biopsy, radiopathomics was a potential strategy for the pretreatment prediction of the TRG in patients with LARC who underwent nCRT. Citation Format: Lizhi Shao, Zhenyu Liu, Lili Feng, Xiaoying Lou, Zhenhui Li, Xiao-Yan Zhang, Xuezhi Zhou, Kai Sun, Da-Fu Zhang, Lin Wu, Guanyu Yang, Ying-Shi Sun, Ruihua Xu, Xiangbo Wan, Xinjuan Fan, Jie Tian. Radiopathomics strategy combining multiparametric MRI with whole-slide image for pretreatment prediction of tumor regression grade to neoadjuvant chemoradiotherapy in rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2014.

Currently, there is no effective single antigen and there are only a very limited number of complex antigens for the diagnosis of early-stage breast cancer (BC). In this study, we used serological analysis of recombinant cDNA expression libraries (SEREX) in combination with phage display technology to screen complex autoantigens from the sera of BC patients. The cDNA expression library was constructed using tissue samples of three patients with BC at as early as stage T1N0M0. The serum samples of ten patients, including the three patients who provided tissue samples, as well as five healthy human subjects as controls were used to screen the library. All seven autoantigens were identified from the library by four rounds of screening and matched the existing genes after a blast search using NCBI-BLAST. Then, the expression conditions of the autoantibodies of the seven autoantigens and anti-CA15-3 in the sera from 100 BC patients and 50 healthy donors were examined by gray values. The data were analyzed by the area under the receiver operating characteristic (ROC) curve and logistic regression diagnostic models. In the end, a panel of complex autoantigens consisting of B11 (LGALS3), B18 (PHB2), B119 (MUC1), B130 (GK2), and CA15-3, which had a sensitivity of 87 % and a specificity of 76 %, were identified. The area under the curve (AUC) of the complex antigens was 0.872, which is significantly greater than that of anti-CA15-3 alone (AUC = 0.634) for the diagnosis of BC. Thus, this panel of complex antigens provides a promising strategy for the diagnosis of early-stage BC.

Angiomotin (Amot) is a multifunctional protein involved in endothelial cell migration and tube formation and angiogenesis. However, the biological role and molecular mechanism for the abnormal expression of Amot in breast cancer is poorly understood. The aim of the present study was to examine the function of and relationship between Amot and the Hippo-Yes-associated protein (YAP) pathway. The expression and location of Amot was examined in breast cancer tissues and cell lines using immunohistochemistry, real-time polymerase chain reaction analysis (RT-PCR), western blotting and immunofluorescence. ANOVA, Student's t-test, Wilcoxon and Chi-square tests were utilized to determine the association of Amot expression with clinically relevant parameters. Stable Amot knockdown MCF-7 cells (MCF-7 Amot KD) were generated to investigate the impact of Amot downregulation on the growth and invasion of MCF-7 cells in vitro. Western blotting was applied to detect the expression of the Hippo-YAP pathway protein in the MCF-7 cells. It was observed that Amot was highly expressed in breast cancer tissues, but weakly expressed in adjacent non-cancerous tissues. Additionally, the expression level of Amot was correlated with that of Ki-67. In MCF-7 cells, Amot downregulation resulted in a significant decrease of cell proliferation and invasiveness. Following Amot knockdown in MCF-7 cells, the expression of YAP, YAP/TAZ and LATS1 was decreased. In particular, the expression of YAP was markedly reduced in the nucleoprotein. The results suggested that Amot was highly expressed in breast cancer tissues and was important in the promotion of breast cancer cell proliferation and invasion. In addition, there was a more intimate connection between Amot and Hippo-YAP pathway.

PURPOSE: To introduce several new ocular biomechanical parameters for comparison between keratoconic and normal eyes using an analysis method based on corneal dynamic deformation video recorded by corneal visualization Scheimpflug technology (Corvis ST; Oculus Optikgeräte GmbH, Wetzlar, Germany). METHODS: This comparative study comprised 52 keratoconic eyes of 43 patients with keratoconus and 52 normal eyes of 52 controls. An analysis method (PolyU [Labview 2009; National Instrument, Austin, TX]) was developed to introduce several new ocular biomechanical parameters and to compare the difference between keratoconic and normal eyes. The repeatability of the new parameters measurement was evaluated and compared with the Corvis ST measurement. Receiver operating characteristic curves were used to establish a cutoff value for the new biomechanical parameters. RESULTS: Intraclass correlation coefficients of the deformation amplitude, peak distance, corneal concave radius of curvature, maximum deformation area, maximum corneal inward velocity and outward velocity (V in, max and V out, max ) were high in both the keratoconic and normal eyes (all intraclass correlation coefficients > 0.75). The measurement agreement of the PolyU analysis method and Corvis ST was good. Most of the biomechanical parameters of patients with keratoconus were significantly different from those of the controls. In the receiver operating characteristic analysis, the V in, max was the best predictive parameter with an area under the curve of 0.79. CONCLUSIONS: The corneal deformation video recorded by the Corvis ST provides useful information for the study of ocular biomechanics. Most of the new ocular biomechanical parameters were significantly different between keratoconic and normal eyes. Further research is needed to develop more comprehensive clinical applications with these new ocular biomechanical parameters. [ J Refract Surg . 2014;30(11):785–791.]

BACKGROUND AND PURPOSE Whether or not migraine can cause cumulative brain alterations due to frequent migraine-related nociceptive input in patients is largely unclear. The aim of this study was to characterize longitudinal changes in brain activity between repeated observations within a short time interval in a group of female migraine patients, using resting-state functional magnetic resonance imaging. METHODS Nineteen patients and 20 healthy controls (HC) participated in the study. Regional homogeneity (ReHo) and functional interregional connectivity were assessed to determine the focal and global features of brain dysfunction in migraine. The relationship between changes in headache parameters and longitudinal brain alterations were also investigated. RESULTS All patients reported that their headache activity increased over time. Abnormal ReHo changes in the patient group relative to the HC were found in the putamen, orbitofrontal cortex, secondary somatosensory cortex, brainstem, and thalamus. Moreover, these brain regions exhibited longitudinal ReHo changes at the 6-week follow-up examination. These headache activity changes were accompanied by disproportionately dysfunctional connectivity in the putamen in the migraine patients, as revealed by functional connectivity analysis, suggesting that the putamen plays an important role in integrating diverse information among other migraine-related brain regions. CONCLUSIONS The results obtained in this study suggest that progressive brain aberrations in migraine progress as a result of increased headache attacks.

Dendritic spines on the dendrites of pyramidal neurons are one of the most important components for excitatory synapses, where excitatory information exchanges and integrates. The defects of dendritic spine development have been closely connected with many nervous system diseases including autism, intellectual disability and so forth. Based on our previous studies, we here report a new functional signaling link between phospholipase D1 (PLD1) and protein kinase D1 (PKD1) in dendritic spine morphogenesis. Coimmunoprecipitation assays showed that PLD1 associates with PKD1. A series of knocking down and rescuing experiments demonstrated that PLD1 acts upstream of PKD1 in positively regulating dendritic spine morphogenesis. Using PLD1 inhibitor, we found that PLD1 activates PKD1 to promote dendritic spine morphogenesis. Thus, we further reveal the roles of the two different enzymes in neuronal development.

Hearing loss following laser-assisted ear surgery has been reported. However, the mechanism responsible for the hearing loss remains largely speculative. The aim of this study was to investigate the correlation between laser-induced hearing loss and changes in the number of hair cell ribbon synapses and ultrastructure in the cochlea. Laser cochleostomy was performed with a superpulsed carbon dioxide (CO2) laser at 2 and 5 W in Sprague–Dawley rats. Auditory brainstem responses (ABRs) were measured preoperatively and 2 days after surgery. The synapse numbers in apical and middle cochlear turns were quantified. Transmission electron microscopy was employed to further examine the subcellular changes in the cochlea. Click and tonal ABR threshold shifts in both 2 and 5-W groups displayed a frequency-dependent loss within the frequency range measured. Laser cochleostomy induced a significant decrease of synapse numbers in the middle turn in both groups (p

In this study we found four CITED2 coding region mutations (c.550G>A, c.574A>G, c.573–578del6) which led to alterations of amino acid sequence (p.Gly184Ser, p.Ser192Gly, p.Ser192fs) in 120 children with congenital heart disease. The CITED2 mutation associated with the dysregulation of HIF-1α, TFAP2c, and CITED2 methylation accompanied with its decrease in mRNA expression might be involved in the pathological process of congenital heart disease.

Objective Prior to this study, the widely used tongue squamous cell carcinoma cell lines could only initiate tumours in immunodeficient mice, which greatly delayed studies on immune function during carcinogenesis. This study established a new tongue squamous cell carcinoma cell line named ‘RSCC-1’, which can initiate tumours in both immunocompetent rabbits and immunodeficient nude mice and has high metastatic ability. Design Primary tongue cancer was induced by DMBA and local mechanical stimulation in New Zealand White rabbits. The induced cancer was serially transplanted into homogeneous rabbits to establish transplanted models. At the same time, cancer samples were collected, cultured and passaged in vitro. Finally, a cell line named ‘RSCC-1’ was established. Its growth behaviour, cell cycle distribution and tumourigenicity in rabbits and nude mice were investigated. Results RSCC-1 cells were cultured continuously in vitro for 19 months (165 passages). They contain between 54 and 196 chromosomes, with a modal number of 75. Tumourigenicity rates were 100% in both homogeneous rabbits and nude mice, with 20% lung metastasis and 50% cervical lymph node metastasis in homogeneous rabbits. Conclusion RSCC-1 is a poorly differentiated, highly malignant rabbit tongue squamous cell carcinoma cell line. Its behaviour in the inoculated animal model closely resembles human tongue cancer, and could metastasise to local lymph nodes and remote organs.

Background/aims This meta-analysis is designed to determine the association between meat consumption and the risk of inflammatory bowel disease. Materials and methods Search relevant literature published in PubMed, Cochrane before July 2015 without restrictions. Studies were included if relative ratios and the corresponding 95% confidence intervals of the risk of inflammatory bowel disease were reported with respect to meat consumption. Results Nine studies were included in this meta-analysis. Relative to those who did not or seldom eat meat, meat consumers had a significantly greater risk of inflammatory bowel disease (pooled relative ratio: 1.50, 95% confidence interval: 1.15-1.95). The funnel plot revealed no evidence for publication bias. Conclusion Meat consumption may increase the risk of inflammatory bowel disease. Additional large prospective studies are warranted to verify this association.

Yan-Wei Shen,1 Xiao-Man Zhang,1 Meng Lv,1 Ling Chen,1 Tian-Jie Qin,1 Fan Wang,1 Jiao Yang,1 Pei-Jun Liu,2 Jin Yang1 1Department of Medical Oncology, 2Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China Background: Premature ovarian failure and infertility following chemotherapy are major concerns for premenopausal women with breast cancer. A potential ovarian function preservation strategy is administration of gonadotropin-releasing hormone (GnRH) agonists during adjuvant chemotherapy; however, studies of the clinical efficacy of GnRH agonists to protect chemotherapy-induced ovarian damage have shown mixed results. Objective: This meta-analysis study was designed to estimate the efficacy of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian damage in premenopausal women with breast cancer. Methods: Electronic literature databases (PubMed, EMBASE, MEDLINE, Cochrane Library databases searching, China National Knowledge Infrastructure, Web of Science, and the Wanfang Data) were searched for relevant randomized controlled trials (RCTs) published until September 2015. Only RCTs that examined the effect of GnRH agonists for chemotherapy-induced ovarian failure in premenopausal women with breast cancer were selected. The rate of spontaneous resumption of menses and spontaneous pregnancy were collected. All data were analyzed by RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark) and Stata 12.0 (StataCorp, College Station, TX, USA). Results: Eleven RCTs with a total of 1,062 participants (GnRH agonists administered concurrently with chemotherapy, n=541; chemotherapy alone, n=521) were included in the meta-analysis. A significantly greater number of women treated with GnRH agonist experienced spontaneous resumption of menses after the adjuvant chemotherapy, yielding a pooled odds ratio of 2.57 (versus chemotherapy alone, 95% confidence interval (CI)=1.65, 4.01; P

Autocrine vascular endothelial growth factor (VEGF) can regulate the survival and progression of cancers through its various receptors. But the mechanisms and mediators for these functions are largely uncovered, especially in breast cancer. We examined the potential roles and mechanisms of VEGF/neuropilin-1 (NRP-1) axis in regulating the tumorigenesis and metastasis of breast cancer and found the expression of VEGF and NRP-1 correlated with aggressiveness of breast cancer. Knockdown of VEGF or NRP-1 inhibited the proliferation, migration and invasion, but enhanced the apoptosis of MDA-MB-231 cells. In contrast, induction of NRP-1 over-expression promoted the proliferation, migration and invasion of MCF-7 cells. VEGF or NRP-1 silencing attenuated the epithelial-mesenchymal transition (EMT) process and the activation of NF-κBp65, but enhanced GSK-3β expression in MDA-MB-231 cells while NRP-1 over-expression reversed the effects in MCF-7 cells. Treatment with hVEGF165 did not change the inhibition in NRP-1 silencing MDA-MB-231 cells, but enhanced the aggressiveness of NRP-1 over-expressing MCF-7 cells. In addition, VEGF-silencing inhibited the growth and metastasis of implanted MDA-MB-231 tumors in vivo. Our novel data suggest that the positive regulation of the VEGF/NRP-1 axis on the tumorigenesis and metastasis of breast cancer may be associated with enhancing the EMT process and the NF-κB and β-catenin signaling. Hence, the VEGF/NRP-1 axis may be a valuable target for design of therapies for intervention of breast cancer.

Functional magnetic resonance imaging (fMRI) has opened a new area to explore the human brain. The fMRI can reveal the deep insights of spatial and temporal changes underlying a broad range of brain function, such as motor, vision, memory and emotion, all of which are helpful in the clinical investigation. In this paper, we introduce some recent-developed algorithms for fMRI signal detection such as model-driven method (general linear model, deconvolution model, non-linear model, etc.) and data-driven method (principle component analysis, independent component analysis, self-organization mapping, clustered constrained non-negative matrix factorization, etc.). We also propose several 'important applications of neuroirnaging and point out their shortcomings and future perspectives.

A number of studies have shown that obesity is implicated in the susceptibility to several cancers. However, the association between obesity and cholangiocarcinoma remains unclear. This meta-analysis aimed to quantitatively assess the association between overweight or obesity and the incidence of cholangiocarcinoma. A literature search was performed for cohort and case-control studies published from 1996 to 2013 using PubMed, Cochrane, and EMBASE databases. Studies were included if they reported odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) of cholangiocarcinoma with respect to obesity or overweight. Normal weight, overweight, and obesity were defined when the body mass index (BMI) was 18.5-24.9, 25-29.9, and ≥ 30 kg/m(2), respectively. Excess body weight was defined as BMI ≥ 25 kg/m(2). Ten studies met the inclusion criteria, which included five cohort and five case-control studies. Compared with normal weight, being overweight (pooled OR 1.30, 95 % CI 1.13-1.49), obesity (pooled OR 1.52, 95 % CI 1.13-1.89), and excess body weight (pooled OR 1.37, 95 %CI 1.22-1.55) were significantly associated with cholangiocarcinoma. The funnel plot revealed no evidence for publication bias. Obesity is associated with the increased risk of cholangiocarcinoma, which needs to be confirmed by long-term cohort studies.

Background Statins protect mesenchymal stem cells (MSCs) against the harsh microenvironment and improve the efficacy of MSC transplantation after acute myocardial infarction (AMI); however, the mechanism remains uncertain. Furthermore, the transdifferentiation potential of MSCs in the post-infarct heart remains highly controversial. The RhoA/Rho-associated coiled-coil-forming kinase (ROCK) pathway participates in many aspects of the damaged heart after AMI and related to the "pleiotropic" effects of statins. This study aimed to explore whether atorvastatin (ATV) facilitates the survival and therapeutic efficacy of MSCs via the inhibition of RhoA/ROCK pathway and subsequently its downstream molecular extracellular regulated protein kinase (ERK1/2), and to investigate the transdifferentiation potential of MSCs in vivo. Methods and results Female rats received myocardial injections of male rat MSCs 30min after AMI. Four weeks after AMI, ATV combined with MSC treatment resulted in improved cardiac function and reduced infarct area. ATV facilitated the MSC survival, as revealed by the increased expression of Y chromosomal genes and the increased number of Y chromosome-positive cells; however, no transdifferentiation markers were observed. ATV inhibited the production of inflammatory cytokines both in vitro and vivo, accompanied by suppression of ROCK and ERK activities. Geranylgeranyl pyrophosphate (GGPP) abrogated the effects of ATV in the H9c2 cells under hypoxia/serum deprivation (H/SD), while the ROCK inhibitor fasudil mimicked the benefits of ATV after AMI. Conclusions ATV improves the post-infarct microenvironment via RhoA/ROCK/ERK inhibition and thus facilitates the survival and efficacy of implanted MSCs. Transdifferentiation may be not responsible for the cardiac benefits that follow MSC transplantation.

BACKGROUND: Delayed vessel healing after drug-eluting stent implantation is thought to be the underlying mechanisms of late stent thrombosis (LST). METHODS AND RESULTS: In the animal model of stenting, 45 minipigs were divided into 3 groups (n=15 each): bare metal stent (BMS), sirolimus-eluting stent (SES), and SES plus atorvastatin treatment (SES+ator). Neointimal coverage and endothelium coverage were evaluated separately by optical coherence tomography (OCT), pathology, and scanning electron microscopy (SEM) at days 7, 14 and 28. OCT showed that SES significantly delayed neointimal coverage compared with BMS and the percentage of uncovered struts in the SES+ator group was significantly decreased on days 7 (42.7±1.3% vs. 56.8±5.7%, P

Scanning electronic microscopy (SEM) observation and GABA irnmunoreactivity of the tissue culture of 6 human embryonic organs of Corti are reported. The normal structural appearance of the hair cells and the facts that there were no bulging of cuticular plates. and cytoplasmic protrusion proved that the hair cells were healthy. After GABA immunostaining, radial bundles, innerspiral bundles, and the ending of inner and outer hair cell regions displayed typical GABA-positive reactivity. The results indicate that the human embryonic organ of Corti is well developed differentiated, and mature at 19 gestational weeks and can continue to grow and differentiate in vitro. The study offers an ideal and important biological model for further research into the human ear.

Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal cells. The cancer-specific pro-apoptotic action of Par-4 is encoded in its centrally located SAC domain. In this study, to further enhance the anti-cancer effect of Par-4 in order to overcome the limitations of peptide therapy, a recombinant adeno-associated virus was constructed using the following strategies: the secretory expression of therapeutic peptide, a HA2TAT-mediated cytosolic delivery technique, and an adeno-associated virus gene transfer system. To test the hypothesis that Par-4 has an additive bystander effect as an anti-cancer therapy, we designed a secretory protein by adding a secretory signal peptide NT4(Si) to the Par-4 SAC-HA2TAT peptide gene sequence [NT4(Si)-Par-4 SAC-HA2TAT]. The results indicated that, compared to the normal NIH3T3 cell line, AAV-NT4(Si)-Par-4 SAC-HA2TAT significantly suppressed cell growth and induced rapid cell death in HepG2 cells in a time-dependent manner through successful gene transfer and secretory expression of therapeutic peptide at 48 h post-transfection. In addition, the secretory properties of Par-4 may greatly increase its effectiveness in cancer therapy when delivered in vivo.

AIM: To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer (ESCC) and the survival of the patients. METHODS: Sixty-four patients (median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy. Each patient received at least two cycles of treatment. The efficacy, side effects and patient survival were evaluated. RESULTS: The partial response (PR) rate was 43.8% (28/64). Stable disease (SD) rate was 47.9% (26/64), and disease progression rate was 15.6% (10/64). The clinical benefit rate (PR + SD) was 84.4%. The main toxicities were leukopenia (50.0%), nausea and vomiting (51.6%), diarrhea (50.0%), stomatitis (39.1%), polyneuropathy (37.5%) and hand-foot syndrome (37.5%). No grade 4 event in the entire cohort was found. The median progression-free survival was 4 mo, median overall survival was 10 mo (95% CI: 8.3-11.7 mo), and the 1- and 2-year survival rates were 38.1% and 8.2%, respectively. High Karnofsky index, single metastatic lesion and response to the regimen indicated respectively good prognosis. CONCLUSION: Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients. The regimen has improved the survival moderately and merits further studies.

Background Stem cell therapy has generated much interest in improving the function of ischaemic myocardium and peripheral tissue, while non-invasively tracking stem cells in vivo is a hurdle for its clinical application. Our group has addressed this concern by developing a bioluminescence tomography (BLT) prototype system with micro-CT (MicroCT) registration approach. In this subsequent study, we aimed to assess the mesenchymal stem cells (MSCs) as well as statins by this multimodality imaging platform and other strategies in the model of peripheral arterial disease (PAD). Methods MSCs were isolated from adipose tissue of the transgenic mice carrying double-fusion reporter genes: firefly luciferase and enhanced green fluorescent protein (Fluc-eGFP). After eGFP flow sorting, 1×10 7 of Fluc-eGFP positive MSCs were injected into the ischaemic hindlimb, created by routine ligation, of the adult nude mice (n=20) with/without rosuvastatin pretreatment. Then we imaged the animals by our 3D BLT and MicroCT modalities as well as a 2D bioluminescence imaging (BLI). Detailed quantitative reconstruction were performed within the mice by adaptive hp finite element method (hp-FEM). Histological and molecular analysis are used to confirm MSCs9 location and angiogenesis. Results 1 week after engraftment, reconstructed BLT total power in MSCs group was 22.4±3.1 nW, while the 2D BLI data was 1.7×10 6 ±2.1×10 5 photons/s/cm 2 /sr. The total power decreased gradually from week 1 to week 6, from mean 22.4 nW to 1.9 nW, demonstrating MSCs9 survival and proliferation. The combined treat by MSCs and rosuvastatin exhibited longer signal and higher power of the MSCs (p 2 =0.93). Moreover, BLT with MicroCT provided detailed 3D images of MSCs and angiogenesis in the hindlimbs. Immunohistology, RT-PCR and Western Blot showed that MSCs with/without rosuvastatin recovered vessel density in contrast to the control and its signal pathway. Conclusions Versatile 3D molecular imaging modalities facilitate the super spatiotemporal visualisation and quantification of the MSCs in the ischaemic hindlimb, while MSCs hold beneficial potential for treating PAD and its survival environment in vivo may be promoted by rosuvastatin.

OBJECTIVE: The objective of this study was to explore the influence of implanted mesenchymal stem cells (MSCs) on cardiac function, structure, and electrophysiology in rabbits with dilated cardiomyopathy (DCM). METHODS: Thirty-eight rabbits were randomly assigned to 3 groups: (1) normal rabbits (n = 12); (2) rabbits with DCM cell implantation (n = 13); or (3) DCM control rabbits (n = 13). Adriamycin was applied to create the rabbit DCM model. Rabbits for cell transplantation received an intramyocardial injection of MSCs. Four weeks later, heart function morphology and electrophysiology changes were observed. The expression of cardiac Troponin T and connexin 43 was investigated through immunohistochemistry. RESULTS: Compared with normal rabbits, the cardiac function of DCM rabbits was impaired, but this impaired function was improved by MSC implantation. The value for monophasic action potential amplitude and the maximum velocity in ¡°0¡±phase decreased significantly in DCM rabbits, whereas the value for 50% monophasic action potential durations (MAPD) and 90% MAPD were increased significantly. The effective refractory period increased also. The comparison of both DCM groups showed that the prolongation of MAPD was shorter in the cell implantation group than in the DCM control group, and no after-depolarization was observed, whereas early after-depolarization was recorded in 2 rabbits in the DCM control group. Histology analysis showed that the structural abnormalities in the cell implantation group were less than those in the DCM control group, and the implanted MSCs could express cardiac Troponin T and connexin 43. CONCLUSIONS: Implanted MSCs can improve heart function, reduce the structural abnormalities, and possibly inhibit the progression of electrophysiologic derangement.

Using electron microscopy and GABA immunohistochemistry we evaluated the effects on human embyronic organ of Corti tissue culture of exposure to the ototoxic aminoglycoside antibiotic neomycin at a dose of 1 mM for 48 to 96 hrs. Neomycin induces the formation of multilamellar myeloid structures. These lesions, found only in the basal coil but both in inner and outer hair cells, were characteristic of the membrane-associated neomycin-induced damage. A large amount of lipofucsin and numerous lipoid vacuoles as well as vesicle-filled mound-like protrusions were also observed after exposure to neomycin. It seems there is no obvious effect on GABAergic innervation.