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Chromosome rearrangement is one of the hallmarks of human malignancies. Gene fusion is one of the consequences of chromosome rearrangements. In this report, we show that gene fusion between solute carrier family 45 member 2 (SLC45A2) and alpha-methylacyl-coenzyme A racemase (AMACR) occurs in eight different types of human malignancies, with frequencies ranging from 45% to 97%. The chimeric protein is translocated to the lysosomal membrane and activates the extracellular signal-regulated kinase signaling cascade. The fusion protein promotes cell growth, accelerates migration, resists serum starvation-induced cell death, and is essential for cancer growth in mouse xenograft cancer models. Introduction of SLC45A2-AMACR into the mouse liver using a sleeping beauty transposon system and somatic knockout of phosphatase and TENsin homolog (Pten) generated spontaneous liver cancers within a short period. Conclusion: The gene fusion between SLC45A2 and AMACR may be a driving event for human liver cancer development.

The long noncoding RNAs (lncRNAs) are widely involved in the progression of various malignant tumors. The current study investigated the role and mechanism of lncRNA melanoma highly expressed noncoding RNA (MHENCR) in colorectal carcinoma. The expression of MHENCR was measured by real-time quantitative reverse transcription PCR (RT-qPCR). The chi-square analysis was used to analyze the correlation between MHECNR and miR-532-3p. Kaplan-Meier curve and multivariate Cox regression analysis were conducted to assess the significance of MHENCR in clinic. The interaction of MHENCR and miR-532-3p was probed using Pearson analysis and dual-luciferase reporter assay. Cellular experiments were implemented to explore the effects of MHENCR/miR-532-3p on colorectal carcinoma cells. Compared with para-cancerous tissues, MHENCR expression was increased and miR-532-3p expression was decreased in tumor tissues. High expression of MHENCR exhibited shorter overall survival. Interfering of MHENCR suppressed cellular activities while the silence of miR-532-3p diminished the decreased cellular behaviors in colorectal carcinoma cells. Interfering with MHENCR expression represses colorectal carcinoma cell proliferation, migration, and invasion by regulating miR-532-3p. MHENCR may act as a novel prognostic marker in colorectal carcinoma and MHENCR/miR-532-3p may serve as a potential target for treating colorectal carcinoma.

Objective To compare the early clinical effects of unilateral biportal endoscopic lumbar interbody fusion (ULIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)on single-segment lumbar stenosis with instability. Methods The patients who had single-segment lumbar spinal stenosis with instability and were treated in our hospital from August 2020 to May 2021 were selected.According to the operation methods,they were classified into ULIF group and MIS-TLIF group.The operation duration,hospital stay after operation,perioperative blood loss (drainage volume 48 h after operation,total blood loss),creatine kinase,inflammatory cytokines (C-reactive protein,interleukin-6),D-dimer,and the incidence of lower-extremity venous thrombosis were compared between the two groups.The visual analogue scale and Oswestry disability index were used to evaluate the functional recovery of the two groups in 1 week,1 month,and 3 months after operation. Results The ULIF group had longer operation duration (

To investigate the differentially expressed genes related to the survival of testicular seminoma patients and the pathogenesis of the malignancy.We obtained the gene expression profiling of testicular seminoma data set GSE8607 from the GEO database and differentially expressed genes in testicular seminoma using the GEO2R online tool. We performed GO and KEGG pathway enrichment via the DAVID website, screened testicular seminoma-related core genes using the STRING and Cytoscape software, and analyzed the survival rate and expression level associated with the core genes through the Kaplan Meier plotter and GEPIA websites.Totally, 591 differentially expressed genes were identified, of which 216 were up-regulated and mainly enriched in 23 biological processes, 8 cell components, 5 biological functions and 7 KEGG pathways, and the other 375 down-regulated and enriched only in the biological process, involving the formation and development of spermatozoa. Thirty-two core genes were obtained via PPI network analysis, including C1QB, CCL2, CCR2, GPR183, ELL, LAPTM5, NPY5R, CD28 and MMP9, which were closely related to the survival rate (P0.05), C1QB, CCL2, CCR2, SELL, LAPTM5, CD28 and MMP9, which were highly expressed in the testicular seminoma tissue (P0.05), and NPY5R, which was lowly expressed in the testicular seminoma tissue (P0.05).The 8 differentially expressed genes identified in the testicular seminoma tissue contribute to effective prediction of the survival rate of the patients as well as to the diagnosis, prevention and treatment of the disease and development of new anti-cancer drugs.

Exosomes of different origins have been found to be protective against ischemic-induced myocardial injury. This study examined the protective effects of circulating exosomes in the mice model of acute myocardial infarction (AMI) and explored the underlying molecular mechanisms. The effects of exosomes on myocardial injury were assessed in the AMI mice model. The in vivo studies showed that circulating exosomes reduced the infarcted size, improved the morphology of heart tissues and also reduced apoptosis of the heart tissues. In addition, the model mice showed an increase in the CD34 + /VEGFR2 + cell population and CD31, CXCR4 and CXCL12 expression after exosomes treatment. MiR-190a-3p was significantly down-regulated in the exosomes derived from the culture medium of hypoxia-treated human cardiomyocytes (HCMs). Further analysis revealed that miR-190a-3p could physically interact with CXCR4/CXCL12 by targeting the respective 3'UTRs. These exosomes could up-regulated CXCR4 and CXCL12 expression in the EPCs; in addition, miR-190a-3p mimics repressed CXCR4/CXCL12 expression in EPCs, while its inhibitor had opposite effects. The in vitro functional assays showed that miR-190a-3p overexpression suppressed the cell viability, proliferation, migration, adhesion and tube formation of EPCs; while miR-190a-3p inhibitor had the opposite effects; exosomes derived from the culture medium of hypoxia-treated HCMs exhibited similar actions of miR-190a-3p inhibitor. Moreover, miR-190a-3p was down-regulated in exosomes from serum in the AMI group when compared to that from sham group. Treatment with exosomes from serum in the AMI group promoted cell proliferation, migration, adhesion and tube formation of EPCs when compared to that in the sham group. More importantly, IT1t attenuated the enhanced effects of miR-190a-3p inhibition on EPC proliferation, migration, adhesion and tube formation. In conclusion, circulating exosomes exerted protective effects on myocardial injury in the AMI mice model, and down-regulation of miR-190a-3p in the circulating exosomes may exert protective effects against myocardial injury. Hypoxia induced the downregulation of miR-190a-3p in the culture medium of HCMs, and the mechanistic investigations indicated that exosomes of hypoxia-conditioned HCM culture medium promoted the cell viability, proliferation, migration, adhesion and tube formation of EPCs via regulating miR-190a-3p/CXCR4/CXCL12 pathway.

Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma (ccRCC)

Developing a non-toxic, super-absorbent and antibacterial hydrogel as a skin wound dressing is of significant importance. Sericin hydrogel is an ideal dressing material as it has excellent biocompatibility, biodegradability, moisture retention, high affinity to biomolecules, self-healing and promoting cell proliferation activity. Here, we blended silk sericin (SS) with poly(vinyl alcohol) (PVA) to prepare a SS/PVA hydrogel through repetitive freeze-thawing. The photoluminescence of SS/PVA hydrogel indicated PVA was well blended with sericin. SS/PVA hydrogel showed excellent hydrophilicity and swelling behavior for its porous structure. PVA blending effectively improved the thermostability of sericin and enhanced the mechanical property of sericin, but did not affect the crystallinity of sericin and PVA. SS/PVA hydrogel exhibited the ability to load and release small molecule drugs and silver nanoparticles. Cytotoxicity and immuno-toxicity assays suggested the gentamicin loaded SS/PVA hydrogel had excellent cytocompatibility on mammalian cells. Bacterial inhibition assay and wound infection model demonstrated the gentamicin loaded SS/PVA hydrogel could effectively inhibit bacterial growth, thus maintain cells viability. This novel hydrogel with antimicrobial activity has shown great potential in wound dressing.

Background Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. Case presentation The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. Conclusion Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Diphthamide is a unique post-translationally modified histidine residue (His715 in all mammals) found only in eukaryotic elongation factor-2 (eEF-2). The biosynthesis of diphthamide represents one of the most complex modifications, executed by protein factors conserved from yeast to humans. Diphthamide is not only essential for normal physiology (such as ensuring fidelity of mRNA translation), but is also exploited by bacterial ADP-ribosylating toxins (e.g., diphtheria toxin) as their molecular target in pathogenesis. Taking advantage of the observation that cells defective in diphthamide biosynthesis are resistant to ADP-ribosylating toxins, in the past four decades, seven essential genes (Dph1 to Dph7) have been identified for diphthamide biosynthesis. These technically unsaturated screens raise the question as to whether additional genes are required for diphthamide biosynthesis. In this study, we performed two independent, saturating, genome-wide CRISPR knockout screens in human cells. These screens identified all previously known Dph genes, as well as further identifying the BTB/POZ domain-containing transcription factor Miz1. We found that Miz1 is absolutely required for diphthamide biosynthesis via its role in the transcriptional regulation of Dph1 expression. Mechanistically, Miz1 binds to the Dph1 proximal promoter via an evolutionarily conserved consensus binding site to activate Dph1 transcription. Therefore, this work demonstrates that Dph1-7, along with the newly identified Miz1 transcription factor, are likely to represent the essential protein factors required for diphthamide modification on eEF2., Author summary Diphthamide is a unique post-translationally modified histidine residue (His699 in yeast, His715 in all mammals) found only in eukaryotic elongation factor-2 (eEF-2). Mice that are deficient in diphthamide biosynthesis are embryonic lethal, attesting to the importance of diphthamide in normal physiology. It has taken four decades to identify the seven non-redundant genes in diphthamide biosynthesis, but whether additional factors are required and how the pathway is regulated remained elusive. To address these issues, we performed two saturating, independent, and unbiased genome-wide CRISPR knockout screens. The screens concluded independently that Dph1-Dph7 and additionally transcription factor Miz1 are the key factors required for diphthamide biosynthesis. Mechanistically, Miz1 binds to the Dph1 proximal promoter via an evolutionarily conserved consensus binding site to activate Dph1 transcription. While diphthamide biosynthesis machinery (Dph1-Dph7) exists across eukaryotes, Miz1 orthologues do not exist in lower species such as yeast, C. elegans, and Drosophila, indicating that the regulation of diphthamide modification by Miz1 emerged much later in evolution. The work opens a new avenue for understanding the role that diphthamide modification plays in normal physiology and bacterial toxin pathogenesis.

PurposeBiomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA).MethodsThree-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0–3 grade) after T12 vertebral augmentation.ResultsIn wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture.ConclusionsThe vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity.

Caffeic acid phenethyl ester (CAPE), extracted from propolis, was proven to inhibit colon cancer. Caffeic acid p-nitro-phenethyl ester (CAPE-pNO2), a derivative of CAPE, was determined to be an anti-platelet agent and a protector of myocardial ischaemia with more potent effects. In the present study, CAPE-pNO2 showed stronger cytotoxic activity than CAPE. We revealed interactions between CAPE-pNO2 and experimental cells. CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. In xenograft studies, CAPE-pNO2 remarkably suppressed tumour growth dose dependently and decreased the expression of VEGF (vascular endothelial growth factor) in tumour tissue. Moreover, HE staining showed that no observable toxicity was found in the heart, liver, kidney and spleen. In addition, metabolites of CAPE-pNO2 in HT-29 cells and organs were detected. In conclusion, para-nitro may enhance the anticancer effect of CAPE by inhibiting colon cancer cell viability, inducing apoptosis and cell cycle arrest via the P53 pathway and inhibiting tumour growth and reducing tumour invasion by decreasing the expression of VEGF; additionally, metabolites of CAPE-pNO2 showed differences in cells and organs.

Specifically targeting genomic rearrangements and mutations in tumor cells has remained an elusive goal in cancer therapy. Here, we use Cas9-based genome editing to introduce the gene for the pro-drug converting enzyme ‘herpes simplex virus type 1 thymidine kinase’ (HSV1-tk) into the genome of cancer cells that carry unique sequences resulting from genome rearrangements. Specifically, we targeted the breakpoints of TMEM135-CCDC67 and MAN2A1-FER fusions in human prostate cancer or hepatocellular carcinoma cells in vitro and in mouse xenografts. We designed one adenovirus to deliver the nickase Cas9D10A and gRNAs targeting the breakpoint sequences and another to deliver an EGFP-HSV1-tk construct flanked by sequences homologous to those surrounding the breakpoint. Infection with both viruses resulted in breakpoint-dependent expression of EGFP-tk and ganciclovir-mediated apoptosis. When mouse xenografts were treated with adenoviruses and ganciclovir, all animals showed reduction of tumor burden with no mortality over the observation period. Our results suggest that Cas9-mediated suicide gene insertion might be a viable genotype-specific therapy for cancer.

Nanomaterials-based drug delivery systems display potent applications in cancer therapy. We synthesized a novel anticancer drug, nano-gold loaded with resveratrol (Res-GNPs), which were characterized using UV-Prove, zetasizer and transmission electron microscope. MTT assay, flow cytometry, TUNEL, immunohistochemistry and western blot analysis were performed to explore the antitumor activity of Res-GNPs in liver cancer cells and tumor xenografts. Res-GNPs showed a stronger effect on inhibiting cell proliferation and promoting apoptosis in Hepg2 cells than that of free Res. Res-GNPs induced apoptosis in Hepg2 cells by down-regulating pro-caspase-9, pro-caspase-3, PI3K and Akt and upregulating caspase-8 and bax. In xenograft studies, Res-GNPs remarkably suppressed tumor growth, promoted tumor apoptosis and decreased the expression of vascular endothelial growth factor (VEGF) in tumor tissue. Furthermore, HE staining showed that no observable toxicity was found in heart, liver, kidney and spleen. The datum confirmed that Res-GNPs possess better antitumor effect than Res

Context: Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative, p-nitro-caffeic acid phenethyl ester (CAPE-NO2), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO2 are related to their absorption properties.Objective: To understand the pharmacokinetic profiles of CAPE and CAPE-NO2 in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells.Materials and methods: The pharmacokinetic profiles of CAPE and CAPE-NO2 were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO2 (5, 10, 20 μM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO2 (5, 20 μM) for 48 and 72 h.Results: The AUC(0−t) of CAPE-NO2 (3239.9 ± 352 ng × h/mL) was two-time greater than CAPE (1659.6 ± 152 ng ...

Bacteria and their toxins are associated with significant human morbidity and mortality. While a few bacterial toxins are well characterized, the mechanism of action for most toxins has not been elucidated, thereby limiting therapeutic advances. One such example is the highly potent pore-forming toxin hemolysin BL (HBL), produced by the gram-positive pathogen Bacillus cereus. However, how HBL exerts its effects and whether it requires any host factors is unknown. Here, we describe an unbiased genome-wide CRISPR/Cas9 knockout screen that identified LPS-Induced TNF-α Factor (LITAF) as the HBL receptor. Using LITAF-deficient cells, a second, subsequent whole-genome CRISPR/Cas9 screen identified the LITAF-like protein CDIP1 as a second, alternative receptor. We generated LITAF-deficient mice, which exhibit marked resistance to lethal HBL challenges. This work outlines and validates an approach to use iterative genome-wide CRISPR/Cas9 screens to identify the complement of host factors exploited by bacterial toxins to exert their myriad of biological effects.

Tauopathy is a complex disorder associated at the junction of several other pathologies. Intrinsically disordered tau protein remains therapeutically challenging due to its undruggable nature and is a possible reason for monumental failure of several tau-based therapies. Herein, nanogold remodeled tau is reported as a pseudo-nanochaperon and shows therapeutic benefit by passive targeting in transgenic tau P301L mutant mice. Treatment with nanogold polyethylene glycol (Au-PEG) conjugate moderately improves the learning ability of the tau P301L mice that corroborates with diminished phosphorylated tau burden. Circulating total tau level that acts in a prion fashion is significantly reduced upon Au-PEG treatment. Similarly, a high level of tau is found in macaque monkey serum and Au-PEG inhibits amyloidosis of Alzheimer's patients and primate's serum samples ex vivo. Addtionally, brain MRI of an old aged macaque monkey shows the decrease of grey matter, which correlates with mutual loss of grey matter upon progressive dementia as reported. Au-PEG tunes tau and other circulating pro-dementia factors that are present in human AD serum, by remodeling the protein and repairing aberrant proteostasis. Alteration of proteotoxic tau function by nanogold as a kinetic stablizer holds translational potential to combat socially challenging dementia.

Structural DNA nanotechnology takes DNA, a biopolymer, far beyond being the molecule that stores and transmits genetic information in biological systems. DNA has been employed as building blocks for the assembly of designed, nanoscaled, supramolecular DNA architectures for applications in biophysics, structure determination, synthetic biology, diagnostics, and drug delivery. Herein, we review a symmetric approach of tile-based DNA self-assembly. This approach allows the construction of DNA nanostructures from minimal numbers of different types of DNA strands based on sequence and structural symmetries. Some examples of the applications of this approach in siRNA delivery are discussed as well.

Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessary to identify the criteria and features of fusion transcripts that are specific for cancer. In this review, we discuss optimization of RNA sequencing depth for fusion transcript discovery and the characteristics of fusion transcripts in normal prostate tissues and prostate cancer. We also propose a new classification of cancer-specific fusion transcripts on the basis of their tail gene fusion protein product and the roles that these fusions may play in cancer development.

Light transmission aggregometry (LTA) is the “gold standard” for platelet function assessment, but it is time-consuming and labor intensive. Recently, an automated platelet aggregation method has been developed on a routine coagulation analyzer (Sysmex CS-2100i). In this study, the performances of CS-2100i including repeatability, correlation with a reference aggregometer (Chrono-log Model 700), and the threshold limitation of platelet counts in platelet-rich plasma (PRP) were evaluated for clinical use. The agonists were adenosine diphosphate (ADP), arachidonic acid, collagen, epinephrine, and ristocetin. The platelet concentration of PRP was adjusted with platelet-poor plasma (PPP) and physiological saline (PS). The CS-2100i showed an excellent repeatability and a strong correlation with the Chrono-log 700 in performing platelet aggregation, and its threshold limitation of platelet counts in PRP was 80 × 109/L. PPP had an inhibitory impact on platelet aggregation induced by ADP, arachidonic acid, collagen or epinephrine; while PS had an inhibitory impact on ristocetin-induced aggregation. PS should be used to adjust PRP for ADP-, arachidonic acid-, collagen-, or epinephrine-induced aggregation; while PPP was recommended for ristocetin-induced aggregation. The CS-2100i showed an excellent repeatability, a strong correlation with Chrono-log 700, a lower platelet count requirement, a shorter turnaround time for samples, the advantage of being a walk-away technology, and the ability to perform a highly standardized platelet function assessment.

The small GTPase Rab26 is involved in multiple processes, such as vesicle-mediated secretion and autophagy. However, the mechanisms and functions of Rab26 in the human pulmonary microvascular endothelial cells (HPMVECs) are not clear. In this study, we thoroughly investigated the role and novel mechanism of Rab26 in permeability and apoptosis of HPMVECs using a self-assembled Rab26 siRNA loaded DNA Y-motif nanoparticle (siRab26-DYM) and Rab26 adenovirus. We found that siRab26-DYM could be efficiently transfected into HPMVECs in a time- and dose-dependent manner. Importantly, the siRab26-DYM nanovector markedly aggravated the LPS-induced apoptosis and hyper-permeability of HPMVECs by promoting the nuclear translocation of Foxo1, and subsequent activation of Toll-like receptor 4 (TLR4) signal pathway. Overexpression of Rab26 by Rab26 adenoviruses partially inactivated LPS-induced TLR4 signaling pathway, suppressed the cell apoptosis and attenuated the hyperpermeability of HPMVECs. These results suggest that the permeability and apoptosis of HPMVECs can be modulated by manipulating Rab26 derived TLR4 signaling pathway, and that Rab26 can be potential therapeutic target for the treatment of vascular diseases related to endothelial barrier functions.

To investigate the method of differentiating dental pulp stem cells (DPSCs) modified by HIF-1α into blood vessels.DPSCs were extracted from teeth samples from 20 patients and were identified by Strol-1 and CD146. DPSCs were divided into experimental group and control group according to DPSCs were modified by HIF-1α not or. HIF-1α-mRNA expression was detected by RT-PCR. HIF-1α, VEGF, SDF-1, Ang-2 and PDGF expression were detected using Western blot in different time after culture for 1 d, 4 d, 7 d and 14 d. Statistical analysis was carried out with SPSS 16.0 software package.Most DPSCs appeared round, oval under phase-contrast microscopy. CD146 and Strol-1 showed green fluorescence. HIF-1α and HIF-1α-mRNA expression became higher with time passing and the difference was statistically significant (P0.05). Compared with the control group, HIF-1α protein and mRNA increased obviously in the experimental group 1d, 4d, 7d and 14d after transfection, and the difference was statistically significant (P0.05). The level of VEGF, SDF-1, Ang-2 and PDGF in the control group was changed unconspicuously, and the expression was not different at different times (P0.05). The level of VEGF, SDF-1, Ang-2 and PDGF in the exprimental group increased, and the difference was statistically significant between different time points(P0.05). Compared with the control group, the level of VEGF, SDF-1, Ang-2 and PDGF in the experimental group was higher 1 d, 4 d, 7 d and 14 d after transfection, respectively, and the difference was statistically significant(P0.05).DPSCs modified by HIF-1α gene can successfully induce vascular differentiation in vitro, which provides foundation for further angioplasty.

Screening of the entire let-7 family of microRNAs (miRNA) by in situ hybridization identified let-7g as the only member, the diminished expression of which was significantly associated with lymph node metastasis and poor survival in breast cancer patients. Abrogation of let-7g expression in otherwise nonmetastatic mammary carcinoma cells elicited rapid metastasis from the orthotopic location, through preferential targets, Grb2-associated binding protein 2 (GAB2) and fibronectin 1 (FN1), and consequent activation of p44/42 mitogen-activated protein kinase (MAPK) and specific matrix metalloproteinases. Treatment with estrogen or epidermal growth factor specifically reduced the expression of mature let-7g through activation of p44/42 MAPK and subsequently stimulated expression of GAB2 and FN1, which, in turn, promoted tumor invasion. We thus identify let-7g as a unique member of the let-7 miRNA family that can serve as a prognostic biomarker in breast cancer and also propose a paradigm used by specific signaling molecules via let-7g to cooperatively promote breast cancer invasion and metastasis. Thus, let-7 family members neither possess equivalent clinicopathologic correlation nor function in breast cancer. Cancer Res; 71(20); 6463–74. ©2011 AACR.

Background: Osteoporotic vertebral compression fractures (OVCFs) commonly afflicts most aged people resulting back pain, substantial vertebral deformity, functional disability, decreased quality of life, and increased adjacent spinal fractures and mortality. Percutaneous vertebral augmentation (PVA) included percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP), nerve block (NB), and conservative treatment (CT) are used for the nonsurgery treatment strategy of OVCFs, however, current evaluation of their efficacy remains controversial. Methods and analysis: A systematic literature search was carried out in PubMed, EMBASE, Web of Knowledge, and the Cochrane Central Register of Controlled Trials up to October 31, 2017. Randomized controlled trials (RCTs) were compared PVP, PKP, NB, or CT for treating OVCFs. The risk of bias for each trial was rated according to the Cochrane Handbook. Mean differences (MDs) with 95% confidence intervals (CIs) were utilized to express VAS (visual analog scale) outcomes. The network meta-analysis (NMA) of the comparative efficacy measured by change of VAS on acute/subacute and chronic OVCFs was conducted for a short-term (

Cellular stress response 1 (CSR1) is a tumor suppressor gene that plays an important role in regulating cell death. In this report, we show that the N-terminus of CSR1 interacts with splicing factor 3A, subunit 3 (SF3A3). The SF3A3 binding motif was identified in the region of amino acids 62-91 of CSR1 through cell-free binding analyses. The interaction between CSR1 and SF3A3 led to migration of SF3A3 from nucleus to cytoplasm. The cytoplasmic redistribution of SF3A3 significantly reduced the splicing efficiency of epidermal growth factor receptor and platelet-derived growth factor receptor. Induction of CSR1 or down-regulation of SF3A3 also significantly reduced the splicing activity of oxytocin reporter gene both in vivo and in vitro. Mutant CSR1 that lacks the SF3A3 binding motif contained no RNA splicing regulatory activity, while the peptide corresponding to the SF3A3 binding motif in CSR1 interfered with the wild-type CSR1 mediated inhibition of RNA splicing. Interaction of CSR1 and SF3A3 is essential for CSR1 mediated cell death. To our knowledge, this is the first report demonstrating that RNA splicing is negatively regulated by redistribution of a splicing factor. © 2016 Wiley Periodicals, Inc.

Cellular stress response 1 ( CSR1 ) is a tumor suppressor gene whose expression was frequently down-regulated in prostate cancer. The mechanism of its down-regulation, however, is not clear. Here, we show that the 3′ untranslated region of CSR1 contains a target site of miR-650. High level of miR-650 was found in prostate cancer samples and cell lines. Degradation of miR-650 by specific inhibitor dramatically increased the expression levels of CSR1. Interaction between miR-650 and its target site in the 3′ untranslated region was validated through luciferase reporter system. Mutation at the target site completely abrogated the activity of miR-650 on the 3′ untranslated region of CSR1. Inhibition of miR-650 reversed the expression suppression of CSR1, suppressed colony formation, and blocked cell cycle entry to the S phase of both PC3 and DU145 cells. Animal model showed significant decrease of tumor volume, rate of metastasis, and mortality of severe combined immunodeficient mice xenografted with PC3 or DU145 cells transformed with inhibitor of miR-650. Our analyses demonstrate that suppression of CSR1 expression is a novel mechanism critical for the oncogenic activity of miR-650.

Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation, reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the synthesized compounds have been characterized by (1)H NMR, (13)C NMR, and HRMS, and tested for the inhibitory ability on platelet aggregation. The results have shown that the ADP (adenosine 5'-diphosphate)-induced platelet aggregation was inhibited by 7a-g with the IC(50) value at 10.14-18.83 μmol/L. Compound 7a exhibited the most potent inhibitory effect (IC(50)=10.14 μmol/L) among all the compounds, but less potent than the control drug ticlopidine (3.18 μmol/L) and aspirin (6.07 μmol/L). The preliminary structure-activity relationship (SAR) was initially investigated in the study.

To analyze and identify the chemical constituents in rat brain tissues after oral administration of Chuanxiong Rhizoma extracts.The dosed and blank rat brain tissues were analyzed by UPLC-Q-TOF-MS. Different peaks were observed in total ion chromatograms and then identified according to their retention time, accurate mass weight, MS and MS/MS data.After oral administration of Chuanxiong Rhizoma extracts, 3 compounds were absorbed into rat brain tissues through BBB. They were identified as senkyunolide I, senkyunolide A and ligustilide.The study is helpful for interpreting effective substance of Ligusticum chuanxiong.

Ligustilide is contained highly or around 1% in such umbelliferous plants as Angelica sinensis and Ligusticum chuanxiong, is one of main bioactive constituents. It shows many pharmacological activities related to their efficacy. At present, ligustilide has attracted extensive attention and more and more studies have been reported, indicating that it is a promising compound. This essay summarizes the progress of pharmacological effects of ligustilide on neuroprotection, vasodilatation, anti-caner and anti-tumor, analgesia and anti-inflammation, and pharmacokinetics including absorption, distribution, metabolism and excretion, providing basis for further studies and development of ligustilide.

To evaluate the efficacy and safety of minimally invasive percutaneous pedicle screw for the management of neurologically intact patients with thoracolumbar burst fractures and posterior ligamentous complex injuries.In the study, 35 patients were reviewed,including 20 males and 15 females, with an average age of 34.1 years (18 to 52), and the mean follow-up for 25.8 months (24 to 36).The duration of surgery was (95.8±12.3) minutes and intraoperative blood loss was (83.0±40.7) mL. There were no major perioperative complications, with the exception of 2 patients who developed a superficial wound infection. LKA and VBH were significantly improved immediately after surgery (P0.001). No significant loss of correction was observed in all the patients(P0.05). Screw misplacement was observed in 9/140 (6.4%) and no patient showed neurological deficit as a result of screw misplacement.The minimally invasive percutaneous pedicle screw has a good clinical outcome in the treatment of thoracolumbar burst fractures with posterior ligamentous complex injury, which could maintain the fracture reduction effectively, and minimize the iatrogenic soft tissue injury.

The flavonoid-metal complexes showed obviously stronger bioactivities such as antibiosis, antivirus, anti-inflammatory, anti-tumor and anti-free-radical, possibly because of the stronger binding force caused by the change in complex structure and accessibility to target spots, or the synergy effect between flavonoids and metallic ions. This essay summarizes studies on bioactivity and mechanism of flavonoid-metal complexes, in order to provide reference for in-depth study and development on effective constituents contained in flavonoid traditional Chinese medicines.

Objective To study synthesis of baicalin-copper and baicalin-aluminium complex and its antimicrobial, anti-tumor activity and anti-tumor effect against macrophages. Method Baicalin was reacted with metallic salt under a weak base condition to produce baicalin-copper and baicalin-aluminium complex. Baicalin and its synthesized complex were detected for antimicrobial activity against Staphylococcus aureus, Hay bacillus, Escherichia coli, Salmonella and Candida albicans by twofold broth dilution technique. Their anti-tumor activity against A549 and IC50 of HepG2 cells and anti-tumor effect against macrophages were detected by the MTT. And their phagocytic effect on macrophages was determined by the neutral red assay. Result The yields of baicalin-copper and baicalin-aluminium complex were 73.93% and 91.08%, respectively. The minimum inhibitory concentration (MIC) value against Staphylococcus aureus, Hay bacillus, Escherichia coli, Salmonella and Candida albicans was 0.0004, 0.0009, 0.0004, 0.0009, 0.000 4 mol x L(-1) for baicalin-copper complex and 0.0011, 0.0011, 0.0011, 0.0011, 0.0005 mol x L(-1) for baicalin-aluminium complex. The IC50 values against A549 and HepG2 cells were 89.6, 22.6 micromol x L(-1) for baicalin-copper complex, and 138.8, 97.2 micromol x L(-1) for baicalin-aluminium complex. The inhibitory ratio of macrophage on A549 cell was 43.52%, 80.89%, 52.66%, respectively, after the macrophages were stimulated by baicalin, baicalin-copper and baicalin-aluminium complex at a concentration of 160 micromol x L(-1). Conclusion The acute toxicity test in mice showed that the complex was nontoxic to mice. Baicalin-copper complex showed the highest antimicrobial, anti-tumor activity, and the strongest effect on the anti-tumor activity of macrophage, while baicalin showed the lowest activities compared with baicalin-copper and baicalin-aluminium complex.

Increased activation of signal transducer and activator of transcription (STAT)-5 has been reported in various malignancies including mammary carcinoma. However, it is only recently that potentially distinct roles of STAT5A and STAT5B in neoplasia have begun to emerge. Herein we systematically delineate the functions of STAT5A and STAT5B in human mammary carcinoma cell lines MCF-7 and T47D. Forced expression of constitutively active (CA) STAT5A enhanced both survival and anchorage-independent growth of human mammary carcinoma cells but concordantly suppressed cell motility as revealed in colony scattering, cell migration, and invasion assays. In contrast, forced expression of CA STAT5B exhibited lower potency than CA STAT5A in enhancing survival and anchorage-independent growth of mammary carcinoma cells and exerted no effects on cell motility. Differential expression of genes that regulate cellular survival and motility was concomitantly observed on forced expression of CA STAT5A or CA STAT5B. Small interfering RNA-mediated depletion of STAT5A significantly impaired anchorage-independent growth of human mammary carcinoma cells, whereas a smaller reduction was observed upon small interfering RNA-mediated depletion of STAT5B. Depletion of endogenous STAT5A also significantly enhanced cell motility, whereas depletion of endogenous STAT5B exhibited no effect. Xenograft studies provided data concordant with the in vitro effects of the two STAT5 isoforms. We therefore demonstrate that STAT5A and STAT5B differentially regulate behavior of human mammary carcinoma cells.

To study the technique and effect of adjunctive cancellous screw in treatment of intertrochanteric fractures with dynamic hip screw (DHS) fixation.Between April 2004 and August 2007, 33 patients with intertrochanteric fracture were treated with DHS fixation and adjunctive cancellous screw. There were 13 males and 20 females, aging 43-82 years with an average age of 67 years. Fractures were caused by traffic accident in 7 patients, by falling from height in 11 patients, by sprain in 15 patients. All fractures were closed. The patients were operated 3-12 days after injury. According to Evans classification, there were 12 cases of type II, 15 cases of type III, and 6 cases of type IV. Twenty-two cases had osteoporosis. Weight bear time and complication were recorded. Fracture healing and neck-shaft angle were observed on radiogram. Hip functions were evaluated using Radford criterion.Thirty-three patients had no intraoperative complications with incision healing by first intension. All patients were followed up from 14 months to 38 months, with an average of 21 months. Fracture healing was achieved within 14 weeks to 21 weeks, with an average of 17 weeks after operations. The neck-shaft angles were (134.2 +/- 13.7) degrees 3 days after operation, (128.6 +/- 8.9) degrees 8 weeks after operation, and (128.5 +/- 9.3) degrees after fracture healing, showing no significant difference when compared with that of the third day after operation (P0.05). According to the Radford criterion at last follow-up, the excellent and good rate of hip function was 93.9% (excellent in 21 cases, good in 10 cases, and poor in 2 cases). Complications such as loosening, breakage, or grievous migration of hardware were not observed.The adjunctive cancellous screw in treatment of intertrochanteric fractures with DHS fixation can provide counteraction of tension and rotation, promote fixation stability, enhance fracture healing and decrease complication.

To elucidate the principal of orthogonal factor analysis, using an example of factor analysis of metabolic syndrome. The basic structures and the fundamental concepts of orthogonal factor analysis were introduced and data involving 1877 women aged of 35-65 years, selected from a cross-sectional study, which was conducted in 1998 - 2001 in Shanghai, were included in this study. Factor analysis was carried out using principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. The different components of the metabolic syndrome were not linked closely with the other components and loaded on the six different factors,which mainly reflected by the variables of obesity, blood pressure, plasma glucose, plasma insulin, triglycerides and HDL-cholesterol respectively. Six major factors of the metabolic syndrome were uncorrelated with each other and explained 86% of the variance in the original data. The factor score and total factor score for the individual could be obtained according to the component score coefficient matrix. Although the components of the metabolic syndrome were related statistically, the finding of six factors suggested that the components of the metabolic syndrome did not show high degrees of intercorrelation. As a linear method of data reduction, the mode reduced a large set of measured intercorrelation variables into a smaller set of uncorrelated factors, which explained the majority of the variance in the original variables. Factor analysis was well suited for revealing underlying patterns or structure among variables showing high degrees of intercorrelation.

To investigate the effect and possible mechanism of lidocaine precondition on calcium overload and apoptosis of the hepatocytes induced by cell hypoxia-reoxygenation.The cultured L02 hepatocytes were randomly divided into 3 groups: a hypoxia-reoxygenation group (Group I), a lidocaine precondition group (Group II), and a normal control group (Group III). After 4 hours of cell hypoxia and 10 hours of reoxygenation, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in the nutritive medium were detected. The cytoplasm ionic calcium concentration was measured by fluoro spectrophotometer. The apoptosis was measured by flow cytometry and fluorescent microscope. The appearance and ultra-microstructure changes of hepatocytes were observed by inverted microscope and electronic microscope.Cytoplasm ionic calcium concentration and apoptosis was positively correlated (r=0.7652, R(2)=0.5855, P0.05). The ALT concentration in the nutritive medium, AST concentration in the nutritive medium, cytoplasm ionic calcium concentration and the ratio of apoptosis of Group I and II were significantly higher than those of Group III(P0.05).The appearance and ultra-microstructure changes of Group I and II were worse than those of Group III. The ALT concentration in the nutritive medium, AST concentration in the nutritive medium, cytoplasm ionic calcium concentration and the ratio of apoptosis of Group II were significantly lower than those of Group I (P0.05). The ultra-microstructure injury of hepatocytes of Group II were less serious than those of Group I.Precondition with lidocaine can attenuate calcium overload of hepatocytes induced by hypoxia-reoxygenation in vitro,and decrease the ratio of apoptosis.

To explore the adult lipid profile of Huayang community from 1998 to 2000 and Caoyang communities in 2001.Representative serum samples of 5628 adults (aged 20 - 95 years) were obtained in Huayang and Caoyang communities during 1998.9 and 2001.11. Standard epidemiology questionnaire, physical check-ups and serum lipids data were analyzed.After standardization to Chinese census statistics of 2000, the age-and sex-standardized means of total cholesterol, HDL-C, LDL-C and triglycerides of the two communities (Huayang vs. Caoyang) were 5.01 mmol/L vs. 4.43 mmol/L, 1.28 mmol/L vs. 1.32 mmol/L, 3.37 mmol/L vs. 2.99 mmol/L, 1.97 mmol/L vs. 1.60 mmol/L respectively, and the age- and sex- standardized prevalence of dyslipidemia was 52.9% vs. 25.1%, and the prevalence for borderline dyslipidemia was 76.0% vs. 56.2%, respectively. The decreasing order of dyslipidemia prevalence of the two communities was: elevated TG, decreased HDL-C, elevated LDL-C and TC. The standardized proportions of optimal HDL-C level were only 15.7% and 16.1% in Huayang and Caoyang respectively which was much lower than these of TG, LDL and TC.The standardized prevalence of adult dyslipidemia and borderline dyslipidemia in the two communities were high. Dyslipidemia of the two communities was TG and decreased.

To study the relationship of Helicobacter pylori (H. pylori) infection with the development and relapse of Henoch-Schonlein purpura (HSP) with gastrointestinal involvement in children.Thirty-six HSP children with gastrointestinal manifestations and 16 of 32 HSP children without gastrointestinal involvement underwent gastroscopy and rapid urease test for H. pylori detection. Thirty healthy children served as the control group. All of the patients received 14C urea breath test and serum H. pylori antibody detections. H. pylori infection was definited when two of detection approaches demonstrated positive.Twenty-one of 36 HSP patients with gastrointestinal manifestations were confirmed with H. pylori infection (58.3%). Of them, the relapsed patients had an H. pylori positive rate of 81.3% (13/16), which was significantly higher than that of the newly diagnosed patients (45.0%, 9/20) (chi(2)=4.49, P0.05). Nine of 32 HSP patients without gastrointestinal manifestations were confirmed with H. pylori infection (28.1%); 2 of 30 healthy children showed H. pylori positive (6.7%, 2/30). There was a significant difference in the H. pylori positive rate among the three groups (chi(2)=14.7, P0.01).H.pylori infection may be associated with the development and relapse of HSP with gastrointestinal involvement in children.

To study the efficacy of esomeprazole-based 1 week or 2 weeks triple therapy for Helicobactor pylori (H. pylori) infection in children.One hundred and five children with H. pylori infection identified by 13C-UBT were randomly assigned into Group A (n=60) and Group B (n=45). The patients of the two groups were administered with 1 week or 2 weeks triple therapy consisting of esomeprazole, clarithromycin and amoxillin, respectively. They were followed up four weeks after drug withdrawal.Recurrent abdominal pain was relieved in all of patients. Fifty-five patients (91.7%) showed 13C-UBT negative in Group A and 42 (93.3%) presented negative in Group B. There was no significant difference in the eradication rate of H. pylori.Esomeprazole-based triple therapy for H. pylori infection is effective in children. The efficacy of esomeprazole-based 1 week or 2 weeks triple therapy for this disorder does not appear to be different.

To study the individual surgical treatment of nasopharyngeal angiofibroma.Between Feb. 1989 and Oct. 2004, different kinds of surgical approaches in 51 patients with angiofibromas were retrospectively analysed. Using Fisch stage: thirty three cases were in stage I and II, 22 cases via palatal approach, 11 cases via endoscopic surgery;18 cases were in stage IIN and IV, 9 cases via lateral rhinotomy approach, 4 cases via midfacial degloving approach + Lefort I approach or modified maxillotomy, 5 cases via craniofacial approach. Twenty three cases accepted the embolization of the artery which feed the tumor, 7 cases in stage IV, 8 cases in stage IlI, 5 cases in stage II, 3 cases in stage I.The average of blood loss was 1010 ml in operation but it became 200 - 870 ml (the average of blood loss was 485 ml) when had a selective preoperative embolization. The blood loss of none selective preoperative embolization was 500 - 3500 ml (the average of blood loss was 1600 ml), t = 7. 48, P0.05, the average of blood loss of selective preoperative embolization is less than the average of blood loss of none selective preoperative embolization. After 9 to 48 months of operation (the average time was 26.4 months), 8 cases recurred one time and 2 cases recurred two times.The preoperative embolization could reduce the amount of bleeding during operation. In patients who are in stage I and II, searching endoscopic surgery could avoid the effect on craniofacial development which traditional surgical procedure did. For patient who are in stage III and IV, midfacial degloving approach and Lefort I approach or modified maxillotomy are not only good for exclusive resection of the tumor but also have less effect on articulation and beautiful cosmetic outlook.

To explore the diagnostic values of vestibular autorotation test (VAT) for patients with vertebrobasilar insufficiency (VBI).VAT and videonystagmography ( VNG) were performed on 73 patients with VBI and 48 patients with peripheral vestibular lesions (contrast group). Parameters analyzed included Gain, phase and asymmetry of VAT, as well as the canal paresis (CP) of caloric test and results of optokinetic-pursuit tests in VNG. Positive result of the test could be defined if anyone of the parameters was abnormal.For VAT test, Gain was enhanced in VBI group and was reduced in contrast group. In VBI group and contrast group, Gain enhanced showed in 47 (64.4%) cases and 5 (10.4%) cases, respectively (chi2 = 31.19, P0.01). Simultaneity, Gain reduced in 11 cases (15.5%) and 22 cases (45.8%), respectively (chi2 = 13.82, P0.01). But there was no statistics significant for results of the parameters of phase, asymmetry and integration between two groups. For VNG test, results with optokinetic-pursuit tests were more abnormal in VBI group than that in contrast group, which showed central lesions characteristics. Forty-four cases (60.3%) in VBI group and 10 cases (20.8%) in control group showed central lesions results with optokinetic-pursuit tests and visual fixation test (chi2 = 15.89, P0.01). Unilateral or bilateral CP showed in 33 cases (68.6%) in control group and 51 cases (69.9%) in VBI group with caloric test.Gain of VAT is mostly enhanced in VBI group, and Gain as a main characteristic is reduced in patients with peripheral vestibular lesions. The Gain parameter is availability for assessing characteristics of vestibular lesions. Phase and asymmetry can be used to assess the vestibular function but can not indicate the characteristics of vestibular lesions.

To investigate the prevalence of peripheral vascular disease (PVD) in patients with diabetes mellitus (DM) and impaired glucose regulation (IGR).Follow-up 5 years after the previous epidemiologic study of metabolic syndrome in Chaoyang community, Shanghai, 2000 - 2001 was conducted among 717 patients with DM or IGR. Questionnaire survey about general status and DM-related history and behaviors, including smoking, was carried out. Physical examination was made. Ankle/brachial index (A/BI) was measured. Intermittent claudication was surveyed by Edinburgh claudication questionnaire (ECQ). Blood sugar and blood lipid were detected. 427 patients, 210 males and 217 females, aged 67.3 +/- 14.0 (21 - 104), with intact data were enrolled into the analysis.The overall prevalence of PVD was 12.2% in the hyperglycemic population. The prevalence of PVD in the diabetics was 15.1%, significantly higher than that of the IGP subjects (7.7%, P = 0.022). The rate of intermittent claudication in those with the A/BIor= 0.9 was 13.5%. Logistic regression revealed that age, sex, diabetic duration, and total cholesterol were independent risk factors of diabetic PVD.The PVD prevalence is rather high in both diabetics and IGR subjects. Most PVD patients are asymptomatic. AB/I measurement helps early diagnosis of PVD.

Bladder cancer related protein (BLCAP) gene was found downregulated most in primary cervical cancer tissues using oncogene/tumor suppressor gene microarray screening in our previous study, therefore this study was to explore the possible correlation between BLCAP gene and cervical cancer.BLCAP expression was investigated in 54 cervical cancer and 25 normal tissues by reverse transcription polymerase chain reaction (RT-PCR). Full length of BLCAP cDNA was cloned into pLXSN expression vector and stably transfected into cervical cancer cell line HeLa cells. Cell proliferation, colony formation ability and apoptosis were determined by cell number counting, colony formation and DNA ladder assay. Nude mice were used to study the anti-tumor effect of BLCAP gene in vivo.BLCAP gene expression was significantly down-regulated or even not observed in human cervical cancer tissues compared to the normal ones. The cell doubling time of HeLa cells transfected with BLCAP was significantly elevated to 69.4 hrs (P0.05), compared to that of the parental cells (27.5 hrs) or cells transfected with empty vectors (30.2 hrs). Moreover, in comparison with control cells, the colony formation efficiency of cells transfected with BLCAP gene was significantly lower (t=5.98, P0.01). BLCAP expression also sensitized Hela cells to apoptosis induced by serum deprivation. In vivo, smaller size of tumors were formed in mice after the injection of cells transfected with BLCAP for 30 days compared to those injected with parental cells or cells transfected with empty vector (tumor wet weights were 1.015 g, 1.612 g, and 1.530 g, respectively, P0.05). Furthermore, under pathological examinations, tumor tissues formed by cells transfected with BLCAP gene displayed less invasive potential with integral vascular fibrous capsules; muscle or adipocyte tissue invasion was not observed. In comparison, necropsy revealed that the tumors formed from the control cells were attached to the underlying muscles; histologically, the neoplastic cells were locally invasive and associated with fibrous connective tissues. These cells exhibited severer cytoplasmic and nuclear pleomorphism compared to cells transfected with BLCAP.BLCAP gene is down-regulated in cervical carcinoma tissues and could suppress tumorigenic ability and growth of HeLa cells, thus it may be a potential suppressor candidate gene of cervical carcinoma.

To investigate the genetic diversity in Chinese populations. And HLA-A, -B alleles and haplotypes of 190 unrelated healthy individuals of Tu nationality from Wufeng county Hubei province were identified for the associated studies of HLA gene polymorphism and disease.The high-resolution typing methods--sequence-based typing(SBT) was used to define the most polymorphism of exons 2 and 3 of the HLA-A, -B locus alleles. The allele and haplotype frequencies were calculated by maximum likelihood estimation with Arlequin software.HLA-A, -B alleles were found to be in Hardy-Weinberg equilibrium(P0.05). A total of 26 HLA-A and 41 HLA-B alleles were detected. The most frequent alleles were A*0201(0.16053), A*110101(0.14737), A*24020101(0.14211), B*4001(0.14737), B*4601(0.13947), followed by A*0207(0.08947), A*0206(0.08158), B*1301(0.07632), B*5801(0.08947), B*1501(0.09737). The frequencies of following alleles to be A*330301(0.05526), B*1502(0.05526), B*3501(0.05263) were all higher than 0.05. The extensive HLA-A-B haplotypes were observed, and the most common haplotypes were A*0202-B*4001(0.04196), A*0201-B*4601(0.03625).In the present study, we first analyzed the HLA-A, B gene typing with SBT, all of these results will be the basic and reference data for Tu race, and also will have the applications available to trace the population migration, clinical organ transplantation, disease-associated study, HLA genetic feature and forensic identification.

To assess the level of language understanding and expression of healthy children aged from 8 to 16 months in urban Beijing and to investigate the children's physical and psychological development conditions and social and economic status of children's family as to identifying the related factors to children's language development and providing a basis for instructing parents child-rearing and promoting early children language development.A quantitative Cross-sectional Study was made. The parents or care givers of 636 healthy young children, randomly stratified and selected in two districts in Beijing were interviewed. T-test was used to compare the scores of language understanding and expression between boys and girls in the same age. Single and multiple factors analysis were used so as to find out the related factors.For boys, the average scores of language were respectively 115.0 for 8 months, 243.0 for 12 months and 410.6 for 16 months; for girls the average scores were respectively 109.9 for 8 months, 286.4 for 12 months and 456.2 for 16 months. The average score of language understanding of boys was higher than that of girls only in the 11 month group. The average scores of language expression of girls were higher than those of boys in 11, 12, 14, 15 month groups. Multiple factors analysis showed that parent-child book reading, parent-child tape listening, higher education level of grandmothers, children' extroversion personality, child being able to speak one word and children's age were positively related to the children' language score.Providing rich language environment should be helpful to early children's language development.

Our previous study has suggested thatthe bladder cancer-associated protein gene (BLCAP) was among the differentially expressed genes in cervical cancer. We confirm here that BLCAP is expressed in all noncancerous cervical tissues (10/10), but it is greatly lost in primary cervical cancer tissue (31/39). In order to further investigate the functional roles of BLCAP, we stably transfected BLCAP cDNA into HeLa cells. The HeLa cells expressing BLCAP show reduced cell growth and clone genicity compared to the vector-transfected cognate cells. BLCAP expression in HeLa cells leads to growth arrest and significantly enhanced apoptosis in vitro and reduced tumor formation in vivo. Thus, BLCAP might be a potential tumor suppressor gene in cervical carcinoma.

Many researchers have conducted studies on child language development and relevant risk factors, but most of these studies were about English-speaking children and few of them were on Chinese-speaking children, and less reports of studies on language development of infants or toddlers are available as compared to those on children above 3 years of age. The objective of this study was to assess the level of vocabulary development of healthy toddlers in urban Beijing and to investigate toddlers' physical and psychological development and socioeconomic status of toddlers' family so as to identify factors related to toddlers' language development and provide basis for instructing parents child-rearing.This is a quantitative cross-sectional study. Using Chinese Communicative Development Inventory mandarin version, (CCDI) and related background questionnaire, a survey was conducted among the parents or care givers of 1056 healthy toddlers (16 approximately 30 months), randomly stratified and selected from two areas of four urban districts in Beijing. The children who were born prematurely, who had low birth weight, or who were deaf, dumb or with disability, were excluded from this study. The mothers who were deaf, dumb or having disability were not included in this study, either. Rank sum test was used to compare the vocabulary scores between boys and girls at the same age. Single and multiple factors analysis were used to find related factors.By 16 months of age, boys could speak about 22 words and girls 84 words on the CCDI. By 29 - 30 months of age, boys could speak about 725 words and girls 752 words on the CCDI. The level of vocabulary development of healthy toddlers in urban Beijing was higher than that reported in previous studies of English-speaking children. Girls had higher vocabulary scores than boys in a few different age groups. Single factor analysis showed that the ages of father and mother, income of father, the language used by care-givers and GDP of the families were factors related to families of toddlers and the age, gender, height, weight and the age at which the toddlers began to speak were factors related to individuals. Multiple factors analysis showed that higher education level of mothers, younger father, earlier beginning of children to speak, toddlers' amiable disposition and emotion, girls, toddlers' age and height positively correlated with toddlers' vocabulary score.The level of vocabulary development of healthy toddlers in urban Beijing is on the high side. Certain individual and familial factors may influence toddlers' language development. It is suggested that health workers should pay attention to the toddlers' language development. The toddlers' parents and caregivers should be taught how to interact with and talk to their children and how to promote children to develop healthy disposition and emotion.

Screening of hollow-organ cancers has been carried out for 16 years using the occult blood test. We are currently assessing the result of serial public cancer screening in China. Human cancers can be divided into 3 types: 1) surface cancer (15%), 2) hollow-organ cancer (65%), and 3) deep-seated solid-organ cancer (20%). Through an education program, the general population was taught to self-examine the body surface and to use a self-examination kit to detect any occult blood discharged from the hollow organs. On discovering positive or doubtful results, these subjects were referred to the hospital for a complete clinical checkup. A total of 10,000 people ages 40 to 70 years chosen from the university areas in Beijing were divided in a test group (5,000) and a control group (5,000). This study, which was carried out for 4 years, showed that 79 cancers were discovered in the test group, with an annual cancer detection rate of 482.5/10,000 population and a cancer mortality rate of 36.6/10,000. The control group showed an annual cancer mortality rate of 206/10,000 population. The difference has very marked statistical significance ( p< 0.001). During the same interval, an extensive cancer screening was carried out in the high-incidence areas. The Cancer Institute in Sihui city of Guangdong province discovered, by screening 758 persons in the outpatient department during a 2-year period, 16 cancers with 15 as nasopharyngeal cancer. From 1999 to 2000, another extensive public cancer screening in the high-incidence areas in Jiangsu province discovered 480 cancers from an 80,000 population. Together with the screening test carried out by Qin's self-examination kit before the National Supported Cancer Research Project on a population of 431,000, 1,272 cancers and more than 10,000 precancerous lesions have been detected. The self-examination kit and public cancer screening are highly important in the practice of public cancer screening.

This is the first report of Rett syndrome in China. Clinical and laboratory data were obtained from 9 girls with Rett syndrome. In addition to the previously reported clinical manifestations (i.e., early deterioration of intelligence, microcephaly, peculiar stereotypic hand movements, and epilepsy), 2 other features were observed in these patients: abnormal evoked response audiometry and low content of the elements, copper and zinc in the hair. The cause of these associated phenomena is unknown.