Efficacy and Safety of 125I Seed Implantation in the Treatment of Pelvic Recurrent Cervical Cancer Following Radiotherapy: A Single-Arm Meta-Analysis of Chinese Patients.

BACKGROUND: The study aimed to assess the efficacy and safety of 125I seed implantation in the treatment of pelvic recurrent cervical cancer following radiotherapy. This meta-analysis was registered in PROSPERO. We looked up relevant studies in the databases of CNKI, Wanfang, CBM, PubMed, Embase, Cochrane Library, and Web of Science. The endpoint measures include the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. RECENT FIDINGS: The meta-analysis included six studies and a total of 246 patients. The pooled ORR of tumor response was 63%, and the DCR was 87%. The median PFS was 9.09 months, and the median OS was 13.46 months. The incidence of adverse events of Grade ≥III was 6%. CONCLUSION: In conclusion, this meta-analysis confirmed that 125I seed implantation has a good local control rate and high safety in the treatment of pelvic recurrent cervical cancer following radiotherapy, and can be used as a remedial treatment for pelvic recurrent cervical cancer following radiotherapy to prolong the survival time of patients. TRIAL REGISTRATION: PROSPERO: CRD42023423857.

Photoacoustic Spectroscopy Gas Detection Technology Research Progress.

Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection.

Noninvasive Imaging OX40+ Activated T Cells Provides Early Warning of Rheumatoid Arthritis.

PURPOSE: The goal of this study was to develop an imaging probe-IRDye-680RD-OX40 mAb-that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable change in T cell activation profiles was observed in early RA. METHODS: OX40 expression pattern was analyzed by flow cytometry. N-hydroxysuccinimide (NHS) esters are used to label proteins selectively on free amino groups of OX40 monoclonal antibody (mAb). Characterization of IRDye-680RD-OX40 mAb was measured and a fluorescence spectrum gathered. Cell binding assay was also performed between activated and naïve murine T cells. Longitudinal near-infrared fluorescence (NIRF) imaging of the probe was performed on day 8, day 9, day 10, and day 11 of adjuvant-induced arthritis (AIA) mouse model. Paw thickness and body weight were compared between the OX40 mAb and IgG injection groups. RESULTS: NIRF imaging with IRDye-680RD-OX40 mAb revealed strong OX40-positive responses with high specificity. Flow analysis showed that OX40 was specifically expressed on the surface of T cells in RP and spleen of AIA model. The AIA group was significantly differentiated from the control group at all time points with imaging monitoring. The region of interest (ROI) was in line with ex vivo imaging and biodistribution study. This study highlights the potential utility of the OX40 NIRF imaging as a new strategy for RA prediction and T cell monitoring. CONCLUSION: The results provide evidence that IRDye-680RD-OX40 mAb detects organized T cells activation in early RA. The optical probe was capable of detection of RA pathogenesis. It identified transcriptional responses to RA that mediate its immune functions. Thus, it may be an ideal probe for RA imaging.

Precise diagnosis and successful surgical intervention of the median arcuate ligament syndrome: A case report.

INTRODUCTION AND IMPORTANCE: The median arcuate ligament syndrome (MALS) is a rare disorder that produces a spectrum of symptoms due to compression of the arcuate ligament, clinically manifested primarily by abdominal pain, nausea, vomiting, and weight loss. The mechanism of these symptoms has not yet been revealed, and the current treatment methods are still somewhat controversial. CASE PRESENTATION: We present a 54-year-old woman who presented with intermittent epigastric pain for nine months. During the onset, she lost 7.5 kg. After routine examinations in a nearby hospital, no abnormality was found. She was referred to us. CTA showed compression of the celiac artery. Further selective celiac angiography at the end of inspiration and expiration confirmed MALS. After consultation with the patient, the decision to have a laparotomy was made. The celiac artery was completely skeletonized, and external compression on the artery was released. Postoperative symptoms improved significantly. One-year follow-up after the operation, she had a weight gain of 4.8 kg and was satisfied with the surgical results. CLINICAL DISCUSSION: The manifestations of MALS are varied and challenging. Our patient presented with weight loss and intermittent abdominal pain. The mutual confirmation of multiple investigations can provide a more comprehensive overview of celiac artery compression. We confirmed using ultrasonography, CT angiography, and selective digital subtraction angiography in this case. The celiac artery compression was relieved after open surgery. Our patient's symptoms improved significantly after surgery. We hope our treatment method can provide a reference for MALS diagnosis and treatment. CONCLUSION: It is challenging to diagnose MALS. Cross-confirmation of multiple examinations can provide a more comprehensive view of celiac compression. Surgical decompression of the celiac artery (open or laparoscopic surgery) may be an effective therapy for MALS, especially in centers with experience.

CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma.

This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with TACE (doxorubicin-lipiodol emulsion) with or without AMD3100. The tumor volume was measured by magnetic resonance imaging (MRI). Histopathological changes were detected by hematoxylin-eosin (HE) staining. HCC cell apoptosis was assessed by terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining. Immunohistochemistry was used to detect the expression of CD34, hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and Ki67. Gene and protein expressions were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Both TACE and AMD3100 reduced the tumor volume in orthotopic rat model of HCC with the decreased CXCR4 expression in tumor tissues, and the combination had better effect. However, TACE increased the microvessel density (MVD) in HCC tissues of rats, while AMD3100 treatment reduced MVD in HCC tissues. AMD3100 reduced the TACE induced MVD in HCC tissues with the reduction of HIF-1α and VEGF expression. Either AMD3100 or TACE could promote HCC cell apoptosis accompanying by decreased cell proliferation, and their combined use had better therapeutic effects. CXCR4 antagonist AMD3100 enhance therapeutic efficacy of TACE in rats with HCC via promoting the HCC cell apoptosis, reducing cell proliferation, and inhibiting MVD, thus reducing tumor volume.

The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis.

Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aß. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 µM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.

Baicalein modulates the radiosensitivity of cervical cancer cells in vitro via miR-183 and the JAK2/STAT3 signaling pathway.

BACKGROUND: Increasing radiosensitivity of cancer cells can enhance the efficacy of cervical cancer treatment. OBJECTIVES: This study evaluated the potential roles and mechanism of baicalein in regulating the radiosensitivity of cervical cancer cells in vitro. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess miR-183 expression in End1/E6E7 cells, Hela cells and Hela cells irradiated with X-ray (0 Gy, 1 Gy, 3 Gy, 5 Gy, and 10 Gy). Cell Counting Kit-8 (CCK-8) method measured cell viability of Hela cells after miR-183 regulation, baicalein or RO8191 treatment. Apoptosis rates were detected using flow cytometry. Thereafter, expression of Bcl-2, Bax and caspase-3 RNA was also detected through RT-qPCR. Protein concentrations of E-cadherin, N-cadherin, Vimentin in epithelial-mesenchymal transition (EMT), phospho-JAK2/STAT3, and total Janus kinase 2/signal transducer and activator of transcription 3 STAT3 (JAK2/STAT3) were examined using enzyme-linked immunosorbent assay (ELISA) methods. RO8191, a JAK2/STAT3 activator, was used to activate the JAK2/STAT3 signaling pathway. RESULTS: The miR-183 expression was significantly lower in Hela cells compared to End1/E6E7 cells. Following upregulation of miR-183 in Hela cells, cell viability was inhibited while apoptosis was promoted. Moreover, EMT was inhibited after miR-183 over-expression. X-ray treatment markedly reduced the cell survival rate and increased miR-183 RNA expression. Baicalein treatment severely reduced the cell viability of 10-Gy X-ray-irradiated Hela cells, partially reversing the effect of miR-183, and also increased apoptosis and prevented EMT in irradiated cells. Y1007/8 in JAK2 and tyrosine (Tyr) residue 705 of STAT3 were phosphorylated, resulting in high expression of JAK2/STAT3, which was decreased by irradiation and baicalein treatment. RO8191 activated JAK2/STAT3 signaling, promoted cell viability and EMT, and inhibited cell apoptosis, while baicalein partly reversed the functions of RO8191. CONCLUSIONS: Baicalein inhibited cell viability and EMT, and induced cell apoptosis of Hela cells, through upregulating miR-183 via inactivation of the JAK2/STAT3 signaling pathway.

Dysregulation of intercellular signaling by MOF deletion leads to liver injury.

Epigenetic mechanisms that alter heritable gene expression and chromatin structure play an essential role in many biological processes, including liver function. Human MOF (males absent on the first) is a histone acetyltransferase that is globally downregulated in human steatohepatitis. However, the function of MOF in the liver remains unclear. Here, we report that MOF plays an essential role in adult liver. Genetic deletion of Mof by Mx1-Cre in the liver leads to acute liver injury, with increase of lipid deposition and fibrosis akin to human steatohepatitis. Surprisingly, hepatocyte-specific Mof deletion had no overt liver abnormality. Using the in vitro coculturing experiment, we show that Mof deletion-induced liver injury requires coordinated changes and reciprocal signaling between hepatocytes and Kupffer cells, which enables feedforward regulation to augment inflammation and apoptotic responses. At the molecular level, Mof deletion induced characteristic changes in metabolic gene programs, which bore noticeable similarity to the molecular signature of human steatohepatitis. Simultaneous deletion of Mof in both hepatocytes and macrophages results in enhanced expression of inflammatory genes and NO signaling in vitro. These changes, in turn, lead to apoptosis of hepatocytes and lipotoxicity. Our work highlights the importance of histone acetyltransferase MOF in maintaining metabolic liver homeostasis and sheds light on the epigenetic dysregulation in liver pathogenesis.

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

Colorectal cancer (CRC) mostly arises from progressive accumulation of somatic mutations within cells. Most commonly mutated genes like TP53, APC and KRAS can promote survival and proliferation of cancer cells. Although the molecular alterations and landscape of some specific mutations in CRC are well known, the presence of a somatic mutation signature related to genomic regions and epigenetic markers remain unclear. To find the signatures from a random distribution of somatic mutations in CRCs, we carried out enrichment analysis in different genomic regions and identified peaks of epigenetic markers. We validated that the mutation frequency in miRNA is dramatically higher than in flanking genomic regions. Moreover, we observed that somatic mutations in CRC and colon cancer cell lines are significantly enriched in CTCF binding sites. We also found these mutations are enriched for H3K27me3 in both normal sigmoid colon and colon cancer cell lines. Taken together, our findings suggest that there are some common somatic mutations signatures which provide new directions to study CRC.

[Research progress on the application of lower limb alignment in discoid meniscus injury].

Discoid meniscus injury is a kind of common sports injury. Its treatment methods include arthroscopic discoid meniscus plasty, discoid meniscus subtotal resection, discoid meniscus total resection and so on. Although the short-term clinical effect is good, the long-term clinical effect is not ideal. At present, different scholars have different views on the choice of surgical methods for discoid meniscus injury. In recent years, many scholars have shown that the choice of operation and the change of lower limb force line are related to the therapeutic effect of discoid meniscus injury. This paper mainly summarizes the current situation of the treatment of discoid meniscus injury and the changes of the force line of the lower limbs after operation, and expounds therole of the evaluation of the force line of the lower limbs in the treatment of discoid meniscus, so as to provide the basis for the clinical individualized treatment of discoid meniscus injury.

Peripheral Vascular Disease and Implication of Nursing Practice: A Brief Literature Review.

Nowadays nurse practitioners are working in several acute hospital settings in different specialized departments. For decades, studies have shown the implications of nurse practice in peripheral vascular disease (PVD) and peripheral vascular intervention (PVI) to have several major benefits. However, there are very limited studies and data on this particular aspect. In this literature review, we briefly discuss the implication of nursing practice in PVD/PVI. This review briefly shows that nursing practice has a major contribution and implication in the treatment of patients with PVD or PVI, especially in patients with diabetes mellitus. From available research, we briefly discuss the implication of nursing practice pre- and postoperatively for PVI. Nurses also contribute significantly in catheter-directed thrombolytic therapy, in smoking cessation programs organized for patients with PVD, and in screening patients for PVD. The vascular nurse practitioners are also involved in providing healthcare advice in order to reduce the risk of disease progression. The major lack of research in this particular field should further inspire scientists to develop and carry out research to further investigate and demonstrate the contribution of nurses in the treatment and management of PVD or PVI, which is gradually becoming a major issue.

Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia.

The protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) plays a critical role in acute leukemias with translocations of the MLL1 gene or with mutations in the nucleophosmin 1 (NPM1) gene. As a step toward clinical translation of menin-MLL1 inhibitors, we report development of MI-3454, a highly potent and orally bioavailable inhibitor of the menin-MLL1 interaction. MI-3454 profoundly inhibited proliferation and induced differentiation in acute leukemia cells and primary patient samples with MLL1 translocations or NPM1 mutations. When applied as a single agent, MI-3454 induced complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia, including patient-derived xenograft models, through downregulation of key genes involved in leukemogenesis. We also identified MEIS1 as a potential pharmacodynamic biomarker of treatment response with MI-3454 in leukemia, and demonstrated that this compound is well tolerated and did not impair normal hematopoiesis in mice. Overall, this study demonstrates, for the first time to our knowledge, profound activity of the menin-MLL1 inhibitor as a single agent in clinically relevant PDX models of leukemia. These data provide a strong rationale for clinical translation of MI-3454 or its analogs for leukemia patients with MLL1 rearrangements or NPM1 mutations.

[The risk factors of periprosthetic fracture after hip arthroplasty:a meta-analysis].

OBJECTIVE: To explore risk factors of the periprosthetic fracture after hip arthroplasty. METHODS: Potential studies were searched in databases including Pubmed, Embase, Cochrane Library, CNKI as well as Wanfang Database up to November 2018 and references in related literatures. The methodological quality of literature was estimated by Newcastle-Ottawa Scale. Raw data were merged and tested mainly by Revmain 5.3. RESULTS: Seventeen studies in total were appropriate with 90 632 patients. The results revealed that it increased the risk of periprosthetic fracture after hip arthroplasty, including female (OR=1.62, 95%CI:1.44 to 1.82, P<0.01), revision(OR=3.78, 95%CI:1.88 to 7.58, P<0.01), preoperative diagnosis of rheumatoid arthritis(OR=1.60, 95%CI:1.07 to 2.37, P=0.02). Conversely, patients involved with cemented prosthesis fixation(OR=0.43, 95%CI:0.27 to 0.68, P<0.01) were less likely to suffer periprosthetic fracture after hip arthroplasty. Other factors were not significantly relevant to periprosthetic fracture after hip arthroplasty, including the age, preoperative diagnosis(femoral head necrosis, osteoarthritis, developmental dysplasia of the hip, femoral fracture, concomitant heart diseases) and American Society of Anesthesiologists >=3. CONCLUSIONS: Orthopedics doctors should constantly be cantious about the risk factors including female, revision and diagnosis of rheumatoid arthritis. They are supposed to prevent the periprosthetic fracture by gentle operation during hip arthroplasty and monitoring the functional exercise after operations when the above risk factors occur.

A temperature-sensitive phase-change hydrogel of tamoxifen achieves the long-acting antitumor activation on breast cancer cells.

Background: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment. Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats. Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes (18F-fluoroestradiol or 18F-fluorodeoxyglucose) by cells in rats' livers and the intrahepatic growth of MCF-7 cells in rats' livers. Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.

Activation of the bile acid receptor GPBAR1 (TGR5) ameliorates interleukin-1ß (IL-1ß)- induced chondrocytes senescence.

Osteoarthritis is the most common chronic condition of the joint disease. Chondrocyte is the sole cell type in joint tissues. Senescence of chondrocytes is known to contribute to the causation of osteoarthritis. Local inflammatory cytokines- caused chondrocytes senescence is proposed to be one of the molecular mechanisms of osteoarthritis. In this study, we show that the bile acid receptor GPBAR1 (TGR5), a G protein couples bile acid receptor, plays important roles in protecting chondrocytes from interleukin 1ß (IL-1ß)- caused senescence. TGR5 is fairly expressed in cultured chondrocytes. Its expression is reduced in isolated chondrocytes from osteoarthritis patients, and IL-1ß treatment suppresses TGR5 expression. Activation of TGR5 by its synthetic agonist, INT-777, dramatically reduces senescence associated ß galactosidase activity by IL-1ß. Mechanistically, the action of INT-777 ameliorates IL-1ß- induced chondrocytes entry of G0/G1 arrest phase and exit of S and G2/M phases. INT-777 inhibits IL-1ß- induced expression of p21, PAI-1, and K382 acetylation of p53 as well as reduction of Sirt1. The knockdown of TRG5 abolished the protective role of INT-777 on these molecules. Collectively, our data indicates that activation of TGR5 is necessary for protection of IL-1ß- induced chondrocytes senescence.

A Single Microorganism Epitope Attenuates the Development of Murine Autoimmune Arthritis: Regulation of Dendritic Cells via the Mannose Receptor.

A single epitope of Leishmania analog of the receptors for activated C kinase (LACK) from Leishmania major, the polypeptide LACK156-173, is recognized by Vß4+/Vα8+ T cells, and activate these cells that drives the subsequent T helper (Th)2 response. This study was undertaken to investigate the therapeutic potential of the LACK156-173 epitope in murine autoimmune arthritis models. To explore the influence of the LACK156-173 epitope on murine collagen antibody-induced arthritis, as well as its immunological mechanism, we vaccinated or treated mice with a LACK156-173 epitope expression plasmid or polypeptide. The effect of LACK156-173 epitope was then evaluated by clinical scores, histopathology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Using flow cytometry, we measured the subsets and maturity of CD11c+ dendritic cells (DCs), as well as T cell polarization, in co-culture experiments. We also measured cytokine gene expression and production. The murine macrophage-like cell line RAW264.7 was used to identify the receptor for the epitope. Vaccination or treatment of the mice with the LACK156-173 epitope expression plasmid or polypeptide ameliorated the severity of arthritis. qRT-PCR analysis revealed that the LACK156-173 epitope improved the balance of effector T cells in synovial tissue compared to that in untreated arthritis controls. Toll-like receptor (TLR) 4 expression was diminished by LACK156-173. The epitope also influenced T cell polarization by regulating the differentiation, maturation, and functions of CD11c+ DCs and upregulating Jagged1 ligand expression. Blocking the mannose receptor (MR) significantly attenuated LACK156-173 epitope-induced macrophage activation. Our data indicate that vaccination or treatment with a single microorganism epitope, LACK156-173, is a highly efficient therapy for murine autoimmune arthritis. The therapeutic effects are mediated by the regulation of the differentiation, maturation, and functions of DCs via MR, resulting in the upregulation of Jagged1 expression and Th2 cell polarization. Our results demonstrate the therapeutic potential of the LACK156-173 epitope in rheumatoid arthritis.

Rapamycin Combi with TAE on the Growth, Metastasis, and Prognosis of Hepatocellular Carcinoma in Rat Models.

INTRODUCTION AND AIM: To investigate the effect of mTOR inhibitor Rapamycin combined with transcatheter arterial embolization (TAE) on the growth, metastasis, and prognosis of hepatocellular carcinoma (HCC) in rat model. MATERIAL AND METHOD: McARH7777 cells were used to construct rat models of HCC, which were randomly divided into Model, Rapamycin, TAE, and Rapamycin + TAE groups. Quantitative reverse transcription-PCR (qRT-PCR) and Western Blot were used to detect the expression of Epithelial-Mesenchymal Transition (EMT)-related molecules, and immunohistochemical staining to determine the expression of EMTrelated proteins, angiogenic factors as well as microvessel density (MVD)-CD34. RESULTS: The hepatic tumor volume of rats in the other three groups were all significantly smaller than the Model group on the 7th, 14th, and 21st day after treatment and the combination treatment was apparently more effective than either treatment alone. Besides, both the number and the size of metastatic nodules of HCC rats after combination treatment were remarkably reduced. In addition, compared with rats in the Rapamycin + TAE group, N-cadherin, Vimentin, HIF-1α, VEGF, and MVD-CD34 were obviously enhanced, while E-cadherin was lowered in those TAE group, which were the complete opposite to the Rapamycin group. Besides, the median survival time of rats in the Rapamycin + TAE group was evidently longer than the resting groups. CONCLUSION: Rapamycin combined with TAE may effectively suppress the EMT formation and angiogenesis, thereby inhibiting the growth and lung metastasis of HCC rats, which provides a new idea for countering the recurrence and metastasis of HCC.

LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145.

LncRNA TUG1, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, its biological function in thyroid cancer cells has not been elucidated. The aim of this study is to measure TUG1 expression level and evaluate its function in thyroid cancer cells. LncRNA TUG1 expression levels in thyroid cancer tissues and three thyroid cancer cell lines (the ATC cell lines SW1736 and KAT18 and the FTC cell line FTC133) were assessed by qRT-PCR and compared with that of the human normal breast epithelial cell HGC-27. MTT assay, colony formation assay, transwell assay and western blot analysis were performed to assess the effects of TUG1 on proliferation, metastasis and EMT formation in thyroid cancer cells in vitro. Rescue assay was performed to further confirm that TUG1 contributes to the progression of thyroid cancer cells through regulating miR-145/ZEB1 signal pathway. LncRNA TUG1 was found to be up-regulated in thyroid cancer tissues and thyroid cancer cells compared with that in the human normal breast epithelial cell HGC-27. Increased lncRNA TUG1 expression was found to significantly promote tumor cell proliferation, and facilitate cell invasion, while down-regulated TUG1 could obviously inhibit cell proliferation, migration/invasion and reverse EMT to MET. These results indicated that TUG1 may contribute to the progression of thyroid cancer cells by function as a ceRNA competitive sponging miR-145, and that lncRNA TUG1 is associated with tumor progression in thyroid cancer cells.

Promotion of peripheral nerve regeneration of a peptide compound hydrogel scaffold.

BACKGROUND: Peripheral nerve injury is a common trauma, but presents a significant challenge to the clinic. Silk-based materials have recently become an important biomaterial for tissue engineering applications due to silk's biocompatibility and impressive mechanical and degradative properties. In the present study, a silk fibroin peptide (SF16) was designed and used as a component of the hydrogel scaffold for the repair of peripheral nerve injury. METHODS: The SF16 peptide's structure was characterized using spectrophotometry and atomic force microscopy, and the SF16 hydrogel was analyzed using scanning electron microscopy. The effects of the SF16 hydrogel on the viability and growth of live cells was first assessed in vitro, on PC12 cells. The in vivo test model involved the repair of a nerve gap with tubular nerve guides, through which it was possible to identify if the SF16 hydrogel would have the potential to enhance nerve regeneration. In this model physiological saline was set as the negative control, and collagen as the positive control. Walking track analysis and electrophysiological methods were used to evaluate the functional recovery of the nerve at 4 and 8 weeks after surgery. RESULTS: Analysis of the SF16 peptide's characteristics indicated that it consisted of a well-defined secondary structure and exhibited self-assembly. Results of scanning electron microscopy showed that the peptide based hydrogel may represent a porous scaffold that is viable for repair of peripheral nerve injury. Analysis of cell culture also supported that the hydrogel was an effective matrix to maintain the viability, morphology and proliferation of PC12 cells. Electrophysiology demonstrated that the use of the hydrogel scaffold (SF16 or collagen) resulted in a significant improvement in amplitude recovery in the in vivo model compared to physiological saline. Moreover, nerve cells in the SF16 hydrogel group displayed greater axon density, larger average axon diameter and thicker myelin compared to those of the group that received physiological saline. CONCLUSION: The SF16 hydrogel scaffold may promote excellent axonal regeneration and functional recovery after peripheral nerve injury, and the SF16 peptide may be a candidate for nerve tissue engineering applications.

Association of estrogen receptor alpha gene polymorphisms and risk of fracture.

The association between estrogen receptor alpha (ESR1) gene polymorphisms and risk of fracture is still controversial and ambiguous. The objective of this study was to evaluate the effect of PvuII polymorphisms of the ESR1 gene on fracture risk in Chinese patients. A population-based control study of elderly subjects was conducted in 120 fracture patients and 120 controls. The PvuII pp genotype of the ESR1 gene was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. There was no relationship between ESR1 gene PvuII polymorphism and fracture risk. When stratifying by fracture type, it was found that vertebral fracture cases had a significantly higher frequency of the PvuII pp genotype (odds ratio=2.00, 95% confidence interval=1.03, 3.88; p=0.04) than controls. This study suggested that there was a modest but statistically significant association between the PvuII pp genotype of the ESR1 gene and vertebral fracture in Chinese patients. The molecular mechanism underlying this association needs further study.