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Polylysines have been frequently used in drug delivery and antimicrobial and cell adhesion studies. Because of steric hindrance, chirality plays a major role in the functional difference between poly-l-lysine (PLL) and poly-d-lysine (PDL), especially when they interact with the plasma membranes of mammalian cells. Therefore, it is speculated that the interaction between chiral polylysines and the plasma membrane may cause different cellular behaviors. Here, we carefully investigated the interaction pattern of PLL and PDL with plasma membranes. We found that PDL could be anchored onto the plasma membrane and interact with the membrane lipids, leading to the rapid morphological change and death of A549 cells (a human lung cancer cell line) and HPAEpiCs (a human pulmonary alveolar epithelial cell line). In contrast, PLL exhibited good cytocompatibility and was not anchored onto the plasma membranes of these cells. Unlike PLL, PDL could trigger protective autophagy to prevent cells in a certain degree, and the PDL-caused cell death occurred

Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

To observe the effect of Qiang Jin exercises on the muscle strength and activity of lumbar spine in patients with lumbar disc herniation.From March 2016 to September 2017, at the Department of Orthopaedics, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, a total of 110 subjects were enrolled, and 98 eligible subjects were screened. The subjects were randomized by stratified randomization and divided into experimental group and control group, 49 cases in each group, 25 males and 24 females in the experimental group, 25 males and 24 females in the control group. The experimental group exercised with Qiang Jin exercises, one time each morning and evening, each time10 sets were made;the control group used classic rehabilitation training, training twice a week, and three months was a course of treatment. After 12 weeks of training, the muscle strength and activity of the lumbar spine were evaluated and compared with the muscle strength and activity of the lumbar spine before training.The experimental group and the control group had different muscle strength and activity of the lumbar spine before and after treatment (Qiang Jin exercises can effectively improve the muscle strength and activity of the lumbar spine and improve the daily living ability of patients.

Immune checkpoint blockade (ICB) therapy is an important treatment option for individuals with cancer, but it has certain limitations. Identifying a better target that can overcome tumor immune escape and stimulate T cell activity is critical. This research aimed to delve into the molecular mechanism underlying the immunoregulatory function of metadherin (MTDH), which is a novel and potential therapeutic target in hepatocellular cancer (HCC). A small interfering RNA library was screened using the luciferase reporter assay and PD-L1 promoter. The Cancer Genome Atlas database and HCC tissues were used to investigate the relationship between MTDH and PD-L1. The association between MTDH and β-catenin/lymphoid enhancer binding factor (LEF-1) was discovered by co-immunoprecipitation. The chromatin immunoprecipitation assay was used to investigate the interaction of MTDH with the PD-L1 promoter when LEF-1 expression was silenced. Locked nucleic acid antisense oligonucleotides (ASOs) were used to inhibit MTDH. We utilized in vitro co-cultures and in vivo syngeneic tumor development experiments to confirm the effectiveness of MTDH ASO combined with PD-1 monoclonal antibody (mAb). MTDH was demonstrated to be a PD-L1 modulator. MTDH increased PD-L1 expression and upregulated PD-L1 transcriptional activity through β-catenin/LEF-1 signaling. More importantly, MTDH ASO improved the anti-PD-1 response and increased cytotoxic T-cell infiltration in PD-1 mAb-treated malignancies. MTDH effectively predicts the therapeutic efficacy of ICB therapy. Our results imply that combining MTDH ASO with PD-1 mAb could be a promising therapeutic strategy for HCC. In addition, MTDH is a potential novel biomarker for predicting the effectiveness of immune checkpoint inhibitor treatment.

Purposes: To evaluate the accuracy of Ophtha Top and consistency between Ophtha Top and IOLMaster 500 in intraocular lens refractive power calculation among cataract patients with normal and long a...

More than 95% of all human genes are alternatively spliced after transcription, which enriches the diversity of proteins and regulates transcript and/or protein levels. The splicing isoforms produced from the same gene can manifest distinctly, even exerting opposite effects. Mounting evidence indicates that the alternative splicing (AS) mechanism is ubiquitous in various cancers and drives the generation and maintenance of various hallmarks of cancer, such as enhanced proliferation, inhibited apoptosis, invasion and metastasis, and angiogenesis. Splicing factors (SFs) play pivotal roles in the recognition of splice sites and the assembly of spliceosomes during AS. In this review, we mainly discuss the similarities and differences of SF domains, the details of SF function in AS, the effect of SF-driven pathological AS on different hallmarks of cancer, and the main drivers of SF expression level and subcellular localization. In addition, we briefly introduce the application prospects of targeted therapeutic strategies, including small-molecule inhibitors, siRNAs and splice-switching oligonucleotides (SSOs), from three perspectives (drivers, SFs and pathological AS). Finally, we share our insights into the potential direction of research on SF-centric AS-related regulatory networks.

Introduction: Papillary meningioma is an extremely rare malignant lesion with high degree of invasiveness, high recurrence rate, and perivascular pseudopapillary structure. The incidence of cystic degeneration in papillary meningiomas is relatively low, and cystic papillary meningiomas growing in the ventricle are even rarer. Here, we present a case of cystic meningioma and review the literature to propose the diagnosis, treatment, immunohistochemical features, and prognosis of the same. Patient concerns: In July 2013, a 35-year-old male Chinese patient presented with dizziness that lasted for a week, without relief. Magnetic resonance imaging (MRI) revealed a 2.0 cm × 1.5 cm × 3.0 cm-sized mass located in the left lateral ventricle trigone. The tumor was small and likely non-malignant. Therefore, the patient received conservative treatment and regular follow-ups. In June 2017, the patient experienced sudden severe headache, dizziness, and vomiting. Diagnosis and intervention: MRI revealed that the mass in the left lateral ventricle trigone had increased to 5.0 cm × 7.0 cm × 8.0 cm over 4 years. The patient underwent surgical resection via the left parietal–occipital approach. Two months postoperatively, the patient received 60 Gy local radiotherapy. The postoperative histopathology suggested that the mass was a cystic papillary meningioma. Outcomes: Two years after the operation, the patient was asymptomatic, and no recurrence of the lesion was noted on MRI. Conclusion: The diagnosis of intraventricular cystic papillary meningioma depends mainly on its histology and imaging features. Total resection and adjuvant radiotherapy can result in a relatively good prognosis of patients with intraventricular cystic papillary meningiomas.

To compare the degeneration of lumbosacral multifidus muscle in patients with lumbar disc herniation.Thirty-five healthy volunteers and 35 patients with unilateral LThe average myoelectric amplitude of the multifidus muscle of healthy volunteers was (48.84±7.77) µV on the left and (49.13±7.86) µV on the right. There was no significant difference between the two sides (Patients with chronic lumbar disc herniation have an imbalance in myoelectric activity, and the muscle strength of the multifidus muscle on the affected side is significantly reduced.

To compare the degeneration of lumbosacral multifidus muscle in patients with lumbar disc herniation.Magnetic Resonance Spectroscopy was performed on the multifidus muscle of 35 healthy volunteers and 35 patients with unilateral LIn healthy volunteers, the proportion of fat on the left side of the multifidus muscle was (0.169± 0.035)%, the proportion of fat removal cross-sectional area on the left side of the multifidus muscle was (0.699±0.070)%, the proportion of fat on the right side of the multifidus muscle was (0.168±0.031)%, and the proportion of fat removal cross-sectional area on the right side of the multifidus muscle was (0.712±0.056)%, there was no significant difference between the two sides (There is degeneration of lumbosacral multifidus muscle on the affected side of patients with unilateral L

There exists considerable evidence conforming that autophagy may play an important role in the biological process of breast cancer. This study aimed to construct and evaluate a novel autophagy-related gene signature as a potential prognostic factor and therapeutic target in breast cancer patients based on high-throughput sequencing datasets.Autophagy-related genes obtained from the Human Autophagy Database and high-sequencing data obtained from The Cancer Genome Atlas (TCGA) were analyzed to identify differential expressed genes (DEGs) between tumor and normal tissues. Then GO and KEGG analysis were performed to explore potential biological and pathological functions of DEGs. Autophagy-related prognostic genes were identified by univariate COX regression analysis. Subsequently stepwise model selection using the Alkaike information criterion (AIC) and multivariate COX regression model was performed to construct autophagy-related gene signature. Then patients were divided into high- and low-risk groups based on the risk score identified by the autophagy-related gene signature. Multivariate COX regression model and stratification analysis were used to specify the prognostic value of this gene signature in whole cohort and various subgroups. T-test and ANOVA analysis were used to compare the expression differences of continuous variables (5 prognostic genes and risk score) in binary and multiple category groups respectively. Kaplan-Meier analysis, log-rank tests and the area under receiver operating characteristic (ROC) curve (AUC) were conducted to validate the accuracy and precise of the autophagy-related gene signature based on GSE20685 and GSE21653 datasets.We profiled autophagy-related DEGs in normal and breast tumor tissues. GO and KEGG analysis indicated that autophagy-related DEGs might participate in breast cancer occurrence, development and drug resistance. Then we identified five autophagy-related genes (EIF4EBP1, ATG4A, BAG1, MAP1LC3A and SERPINA1) that had significantly prognostic values for breast cancer. Autophagy-related gene signature was constructed and patients were divided into high- and low- risk groups based on their risk score. Patients in the high-risk group tended to have shorter overall survival (OS) and relapse-free survival (RFS) times than those in the low-risk group (OS: HR = 1.620, 95%CIs: 1.345-1.950; P 0.001; RFS: HR = 1.487, 95%CIs: 1.248-1.771, P 0.001). Autophagy-related gene signature had significant prognostic value in stratified subgroups especially in advanced breast cancer subgroups (T3-4; N2-3; stage III-IV). Its prognostic value was further confirmed in two GEO validation datasets (GSE20685: P = 6.795e-03; GSE21653: P = 1.383e-03). Finally, association analysis between clinicopathological factors and gene signature showed the risk score was higher in patients with ER/PR negative, higher clinical stage or T stage (P 0.01).We established and confirmed a novel autophagy-related gene signature for patients with breast cancer that had independent survival prognostic value especially in advanced breast cancer subgroups. Our research might promote the molecular mechanism study of autophagy-related genes in breast cancer.

A rasagiline transdermal patch can be used to offer continuous rasagiline to patients with Parkinson's disease who cannot take their usual oral medications. This was the first study to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. Thirty subjects were randomized to 3 groups with 10 subjects in each group. The 10 subjects of group 1 received a single 1-mg dose of rasagiline as a tablet; the 20 subjects of groups 2 and 3 received a single transdermal patch (48-hour patch-on period) containing 1.25 mg and 2.5 mg rasagiline, respectively. After a 2-week washout period, the subjects of group 1 were assigned to receive 1 mg of rasagiline tablets every 24 hours for 7 days, and the subjects of group 2 were assigned to receive 1.25-mg rasagiline transdermal patches (48-hour patch-on period) every 72 hours for 5 time periods. The absorption of rasagiline from the transdermal patch was significantly improved, although the peak plasma concentration was obviously reduced. There was slight accumulation of rasagiline dose after multiple administrations. Inhibition of platelet monoamine oxidase-B (MAO-B) activity was dose dependent. The 80% inhibition maintained for at least 48 hours after multiple-dose administration of 1 mg tablets, and for 72 hours after multiple-dose administration of 1.25 mg/48 h patch. Compared with rasagiline tablets, the transdermal patch had a prolonged duration of 80% inhibition and increased maximal inhibition of MAO-B activity. These characteristics permitted an interval of 3 days of dosing, which was convenient for patients to use.

Laparoscopic methods and fast-track surgery (FTS) can enhance recovery and reduce postoperative hospital stay. However, whether laparoscopic surgery can provide short-term benefits within FTS is controversial. Thus, we conducted a meta-analysis of published studies to evaluate the effect of laparoscopic colorectal surgery within FTS. We searched PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies. Endpoints were duration of postoperative hospital stay, time to first bowel movement, total postoperative complication rate, readmission rate, mortality within 30 days after surgery, and conversation rate of laparoscopic surgery. Four randomized controlled trials and six clinical controlled trials (1510 patients) were eligible for analyses. Duration of postoperative hospital stay (weighted mean difference, –1.65 days; p

Levator resection surgery is commonly performed to correct ptosis, and a large number of postoperative complications are well known. This report presents a previously unreported complication of marginal ectropion after levator resection surgery for congenital ptosis.The three patients with upper eyelid marginal ectropion in this observational case series previously had undergone levator resection surgery for congenital ptosis. The patients' medical records and clinical photographs were reviewed retrospectively. The patients underwent reoperations for ectropion correction. Unusual tissues identified during the surgery were excised and processed for histopathologic analysis.The patients presented with upper eyelid marginal ectropion and had a history of levator resection surgery for congenital ptosis on the same eye. Ingrown tissues were observed during the second operations for ectropion correction in all three patients. Histopathologic analysis was performed for two of the patients, confirming that the tissue consisted of mucosa. The ectropions were corrected after surgical removal of the ingrown tissues.Marginal ectropion can occur after levator resection surgery. In this study, the ectropion was attributed to mucosal ingrowth, a complication not previously reported. To improve the surgical outcomes, surgeons should be aware of this complication.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A xenograft brain tumor model was established by the subcutaneous injection of U87MG cells into nude mice to investigate the efficacy of a non-viral vector, arginine-modified polyamidoamine dendrimer (PAMAM-R), in delivering a therapeutic gene, human interferon beta (IFN-β). We used 4',6-diamidino-2-phenylindole staining, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and the caspase-3 activity assay to determine the induction of apoptosis upon transfection with the PAMAM-R/IFN-β gene polyplex in vitro. The polyplex was injected into xenograft brain tumors. Mice treated with PAMAM-R/pORF-IFN-β exhibited a significantly smaller tumor size than control mice and PAMAM-R/pORF treated mice. Hematoxylin/eosin staining and immunohistochemistry with the endothelial growth factor receptor antibody also revealed inhibition of tumor growth. Furthermore, reverse transcription polymerase chain reaction and the TUNEL assay also verified the expression of IFN-β and induction of apoptosis in vivo. These results indicate that the PAMAM-R/pORF-IFN-β polyplex is an effective therapeutic candidate for glioblastoma multiforme due to its selective induction of apoptosis in tumor cells.

The safety and feasibility of laparoscopic splenectomy and esophagogastric devascularization are still uncertain. The aim of this study was to compare our results for laparoscopic splenectomy and esophagogastric devascularization with those for open splenectomy and esophagogastric devascularization. From January 2008 to December 2011, 153 patients were diagnosed with portal hypertension and serious gastroesophageal varices in our institute, among which, 107 patients also had repeated upper gastrointestinal bleeding and 85 had severe hypersplenism. Eighty patients chose laparoscopic splenectomy and esophagogastric devascularization and 73 patients underwent the open procedure. Results and outcomes were compared retrospectively. Nine patients underwent conversion to laparotomy in the laparoscopic group. We compared the laparoscopic group (80 patients) and the open group (73 patients). Operating times and the frequencies of blood transfusions were similar. Blood loss was less (P = 0.044), the passing of flatus was earlier (P = 0.041), and hospital stays were shorter (P = 0.028) in the laparoscopic group. Portal vein system thrombosis after laparoscopy was more frequent (P = 0.012) but the rates of main trunk occlusion were similar between the two groups. Pleural effusion after laparoscopy was less (P = 0.021) and, apart from this, there was no difference in other morbidities between the two groups. During a postoperative follow-up period of 2 to 50 months in 80 patients of the laparoscopic group vs. 73 patients of the open group, the incidence of esophagogastric variceal rebleeding, encephalopathy, and secondary liver cancer showed no significant differences. And the mortality rates for each of the groups were not different. The short-term effects of laparoscopic splenectomy and esophagogastric devascularization were better than those for open surgery, and the medium-term effects were similar between these two surgical approaches. Prospective randomized studies with a greater number of cases are needed to confirm the role of laparoscopy in splenectomy and esophagogastric devascularization.

Background: The authors devised a double-bundle posterior cruciate ligament reconstruction technique in combination with a single-sling method. However, the double-bundle technique needs more simplicity and a decreased possibility of failure. Hypothesis: A novel surgical technique of transtibial double-bundle posterior cruciate ligament reconstruction using a single-sling method with a tibialis anterior allograft, previously introduced, produces satisfactory results. Study Design: Case series; Level of evidence, 4. Methods: Twenty-one patients who underwent double-bundle transtibial isolated posterior cruciate ligament reconstruction using a single-sling method between July 2003 and September 2007 were enrolled in this study. The exclusion criteria applied were (1) a multiligamentous injury, (2) posterior cruciate ligament reconstruction previously performed using another technique, and (3) the presence of any additional injury capable of affecting knee stability. The Lysholm and International Knee Documentation Committee (IKDC) knee scales were used for the clinical outcome evaluation. Stability was evaluated using a KT-2000 arthrometer. The evaluation was performed by comparing preoperative and last follow-up results. Results: Nineteen men and 2 women were enrolled, with a mean follow-up of 49.2 months (range, 25-73 months). The mean Lysholm score was 53 ± 5.3 (range, 34-68) preoperatively and improved to 83.5 ± 13 (range, 61-97) at the last follow-up after surgery ( P < .001). The IKDC score also improved from preoperative (0 A, 0 B, 7 C, 14 D) to final follow-up (8 A, 9 B, 3 C, 1 D; P < .001). Mean side-to-side difference in posterior translation, measured using the KT-2000 arthrometer, was 13.5 ± 1.2 mm preoperatively and 3.4 ± 0.8 mm at last follow-up evaluations (mean 51.7 months postoperatively). Conclusion: After follow-up for longer than 24 months, the transtibial double-bundle posterior cruciate ligament reconstruction with a single sling was found to produce satisfactory clinical and stability results, which indicates that the described technique should be viewed as a viable alternative.

We synthesized biodegradable b-PEIS (branched poly(ethylenimine sulfide)) by crosslinking linear PEIS. We controlled the degree of crosslinking and molecular weight by adjusting the amount of the crosslinker, bisepoxide. The b-PEIS was readily degradable under reductive conditions (5mm glutathione solution) and the degradation time was dependent on the degree of crosslinking. We controlled the molecular weights of the b-PEIS by regulating the amount of crosslinker and thus, the degree of crosslinking. Our titration data showed that there was almost no loss in buffering ability before or after bisepoxide crosslinking. We verified the degradation of this polymer by MALLS and gel electrophoresis, and confirmed that there was a high transfection efficiency and low cytotoxicity based on cellular data. Intracellular trafficking was observed by image restoration microscopy, demonstrating that b-PEIS does not accumulate in the cell interior.

Objective To investigate the role(s) of Trps1 in non-anastomotic biliary stricture (NABS) following liver transplantation. Methods Immunohistochemical and histological techniques were used to detect Trps1, E-cadherin, CK19, vimentin, α-SMA, and collagen deposition. Human intrahepatic biliary epithelial cells (HIBECs) were infected with a Trps1 adenovirus, or transfected with Trps1 short-interfering RNAs (siRNAs). Reverse transcription polymerase chain reaction (RT-PCR) assays and western blotting were used to determine expression levels of epithelial and mesenchymal markers, and Trps1 in HIBECs. Results Expression of Trps1 and epithelial markers was down-regulated or absent in NABS liver samples. Mesenchymal markers were seen in biliary epithelial cells (BECs), with collagen deposited around the bile duct. Trps1 expression positively correlated with epithelial markers. Expression of epithelial marker mRNAs and proteins in HIBECs decreased with prolonged cold preservation (CP), while mesenchymal marker expression increased. A 12-h CP period led to increased Trps1 mRNA and protein levels. Expression of E-cadherin was increased in HIBECs following Trps1 adenovirus infection and CP/reperfusion injury (CPRI), with vimentin expression levels reduced and CPRI-mediated epithelial-mesenchymal transition (EMT) inhibited. Transfection of HIBECs with Trps1 siRNAs in conjunction with CPRI revealed that E-cadherin expression was decreased, vimentin expression was increased, and CPRI-mediated EMT was promoted. Conclusion Trps1 is involved in NABS pathogenesis following liver transplantation and negatively correlates with BEC EMT and biliary fibrosis in liver grafts. Trps1 demonstrates antagonistic effects that could reverse EMT.

Background We describe four cases of primary lacrimal adenoid cystic carcinoma (ACC) treated with neoadjuvant intra-arterial chemotherapy (NAIC). Methods The outcomes and complications of NAIC were reviewed. Several treatment-related local and/or systemic complications were noted. Results One patient experienced ipsilateral eyelid and eyeball necrosis and permanent facial palsy; the second patient developed ipsilateral facial swelling and jaw claudication; and the third patient had febrile neutropenia, cellulitis, and phlebitis. These three patients underwent total exenteration. The fourth patient experienced neutropenia and thrombocytopenia and underwent tumour removal without exenteration. All patients were followed for more than 4 years and were alive at the last follow-up. Conclusion Neoadjuvant intra-arterial chemotherapy may be an alternative treatment that will improve the survival rate of ACC. However, careful and close observation is needed to minimise the risk of side effects. Further investigations are needed to justify the use of chemotherapy-related treatments and the associated costs.

Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients with cancer with biomarker detection. To investigate the prognostic and predictive values of cyclin D1 expression in patients with oral squamous cell carcinoma (OSCC) who were treated in a prospective, randomized, phase III trial evaluating standard treatment with surgery and postoperative radiotherapy preceded or not by induction docetaxel, cisplatin, and 5-fluorouracil (TPF), immunohistochemical staining for cyclin D1 was conducted in pretreatment biopsy specimens of 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Cyclin D1 index was estimated as the proportion of tumor cells with cyclin D1 nuclear staining. A low cyclin D1 expression predicted significantly better overall survival (OS; P = 0.001), disease-free survival (P = 0.005), locoregional recurrence-free survival (P = 0.003), and distant metastasis-free survival (DMFS; P = 0.002) compared with high cyclin D1 expression. Cyclin D1 expression levels were not predictive of benefit from induction TPF in the population overall. However, patients with nodal stage cN2 whose tumors had high cyclin D1 expression treated with TPF had significantly greater OS (P = 0.025) and DMFS (P = 0.025) when compared with high cyclin D1 cN2 patients treated with surgery upfront. Patients with low cyclin D1 level or patients with cN0 or cN1 disease did not benefit from induction chemotherapy. This study indicates that cN2 OSCC patients with high cyclin D1 expression can benefit from the addition of TPF induction chemotherapy to standard treatment. Cyclin D1 expression could be used as a biomarker in further validation studies to select cN2 patients that could benefit from induction therapy. Mol Cancer Ther; 12(6); 1112–21. ©2013 AACR.

Endoscopic sinus surgery is a popular surgical treatment for chronic sinus disease. Despite improved surgical techniques, postoperative orbital complications can occur, including extraocular muscle injury. We report the case of a 62-year-old woman who suffered from medial rectus muscle transection after transnasal endoscopic ethmoidectomy. She was successfully managed with periorbital globe fixation.

BACKGROUND: Calcium phosphate cement (CPC) can be molded or injected to form a scaffold in situ, which intimately conforms to complex bone defects. Bioactive glass (BG) is known for its unique ability to bond to living bone and promote bone growth. However, it was not until recently that literature was available regarding CPC-BG applied as an injectable graft. In this paper, we reported a novel injectable CPC-BG composite with improved properties caused by the incorporation of BG into CPC. MATERIALS AND METHODS: The novel injectable bioactive cement was evaluated to determine its composition, microstructure, setting time, injectability, compressive strength and behavior in a simulated body fluid (SBF). The in vitro cellular responses of osteoblasts and in vivo tissue responses after the implantation of CPC-BG in femoral condyle defects of rabbits were also investigated. RESULTS: CPC-BG possessed a retarded setting time and markedly better injectability and mechanical properties than CPC. Moreover, a new Ca-deficient apatite layer was deposited on the composite surface after immersing immersion in SBF for 7 days. CPC-BG samples showed significantly improved degradability and bioactivity compared to CPC in simulated body fluid (SBF). In addition, the degrees of cell attachment, proliferation and differentiation on CPC-BG were higher than those on CPC. Macroscopic evaluation, histological evaluation, and micro-computed tomography (micro-CT) analysis showed that CPC-BG enhanced the efficiency of new bone formation in comparison with CPC. CONCLUSIONS: A novel CPC-BG composite has been synthesized with improved properties exhibiting promising prospects for bone regeneration.

Summary Objectives Functional role of Annexin A1 in tumorigenesis is poorly understood. The aim of this study was to investigate the relationship between Annexin A1 protein expression and pathological differentiation grade in biopsy samples from a large cohort of patients with oral squamous cell carcinoma (OSCC); and to evaluate the potential role of Annexin A1 on cell proliferation and tumorigenesis of OSCC. Materials and methods We investigated the relationship between Annexin A1 expression by immunohistochemical staining and pathological differentiation grade of biopsy samples from 232 OSCC patients, and the relationship between Annexin A1 expression and cell proliferation as well as tumor formation using both in vitro and in vivo OSCC models. Results Annexin A1 expression correlated significantly with pathological differentiation grade in OSCC patients, a lower Annexin A1 expression correlating with a poorer differentiation grade. Forced Annexin A1 overexpression in OSCC cell lines, CAL27 and Tca8113, significantly reduced the cell proliferation whereas down-regulation of Annexin A1 expression in OSCC cell line, HB96, significantly increased proliferation of HB96 cells. Tumors formed from CAL27 cells overexpressing Annexin A1 grown significantly slower compared to the parental CAL27 cells in nude mice and showed a significantly reduced nuclear Ki-67 labeling index. Interestingly, these tumors also showed a well differentiated histology pattern whereas the tumors formed from the parental cells were consistently moderately differentiated. Conclusions These data support a significant correlation between Annexin A1 expression and pathological differentiation grade, and a functional role of Annexin A1 in inhibiting cell proliferation and cell differentiation in OSCC.

Background Approximately 60–80% of patients with advanced head and neck squamous cell carcinoma (HNSCC) die within five years after diagnosis. Cisplatin-based chemotherapy is the most commonly used palliative treatment for these patients. To evaluate the prognostic value of X-linked inhibitor of apoptosis (XIAP) level as a potential biomarker in these patients, we investigated the relationship between XIAP expression and cisplatin response of these patients and their prognosis. Methodology/Principal Findings Sixty patients with advanced HNSCC were recruited in this study. Expression of XIAP was examined both before and after chemotherapy and was correlated with chemotherapy response, clinicopathology parameters and clinical outcomes of the patients. We found that XIAP was expressed in 17 (20.83%) of the 60 advanced HNSCC samples and the expression was significantly associated with cisplatin resistance (P = 0.036) and poor clinical outcome (P = 0.025). Cisplatin-based chemotherapy induced XIAP expression in those post-chemotherapy samples (P = 0.011), was further associated with poorer clinical outcome (P = 0.029). Multivariate analysis demonstrated that only alcohol consumption, lymph node metastasis and XIAP level were independently associated with the prognosis of advanced HNSCC patients. Inhibiting XIAP expression with siRNA in XIAP overexpressed HNSCC cells remarkably increased their sensitivity to cisplatin treatment to nearly a 3 fold difference. Conclusions/Significance Our results demonstrate that XIAP overexpression plays an important role in the disease course and cisplatin-resistance of advanced HNSCC. XIAP is a valuable predictor of cisplatin-response and prognosis for patients with advanced head and neck cancer. Down-regulation of XIAP might be a promising adjuvant therapy for those patients of advanced HNSCC.

Disheveled associated activator of morphogenesis 2 (DAAM2) is one of the key proteins of WNT/plantar cell polarity signaling pathway which is closely linked to oncogenesis, cellular proliferation and regeneration, and stem cell renewal. This study investigated the association of DAAM2 genetic polymorphism with the clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We selected candidate single nucleotide polymorphisms (SNPs) by DNA chip analysis using Illumina Infinium Human-1 microarrays™ on 15 patients who underwent allogeneic HSCT with (N = 7) or without (N = 8) acute graft versus host disease (GvHD). Six SNPs (rs2504787, rs2504086, rs2504082, rs3004067, rs882559, and rs3004070) of DAAM2 were associated with acute GvHD prevalence, and the genotyping was extended to larger population (N = 228). Medical records were reviewed to see the correlation of these SNPs with the clinical outcomes of the patients. In rs2504082 and rs882559, treatment-related mortality was significantly lower in major homozygote than other genotypes (29.3% in AA vs. 44.3% in AG or GG, p = 0.0214; 23.0% in CC vs. 39.9% in CG or GG, p = 0.0072, respectively). Acute GvHD incidence and engraftment time were significantly different according to the specific genotype of selected SNPS in this study. This study is the first report regarding the clinical value of DAAM2 polymorphism as a predictive marker of clinical outcomes of allogeneic HSCT.

J Oral Pathol Med (2010) 39 182–187 Background: Candida albicans is the important opportunistic fungal pathogens which can cause oral Candidiasis and even more seriously systemic infection. Apoptosis of C. albicans induced by environmental factor such as weak acid and antifungal drugs were studied recently. Illustrating the phenomenon of apoptosis in C. albicans may help us to discover new antifungal therapy by activating the fungal cells to suicide. Methods: Two oral C. albians clinical isolates which isolated respectively from healthy host [Strain 23C: minimal inhibition concentration (MIC) is 0.125 μg/ml for Amphotericin B (AmB)] and advanced cancer patient (Strain 28A: MIC is 2 μg/ml for AmB), were induced by 1 μg/ml AmB in vitro for 200 min, and then studied the apoptosis markers using terminal deoxynucletidyltransferase-mediated dUTP nick end labeling (TUNEL) (shown by diaminobenzidine and fluorescent isothiocyanate), and the ultrastructure of cell nuclear using transmission electron microscope (TEM), quantitative analysis using flow cytometry for the rapid exposure of phosphatidylserine at the outer membrane and propodium iodide (PI) double staining. C. albicans conference strain YEM30 was used as the control strain. Results: With TUNEL assay and TEM, we detected the typical characteristics of apoptosis. Strain 23C (with low MIC) showed significantly higher percentage of apoptosis (19.92%) compared with Strain 28A (with high MIC) which was isolated from the cancer patient (7.29%) (P

Candida albicans is one of the main opportunistic pathogen for human , the aim of this study is to investigate the phenomena of apoptosis in oral Candida albicans induced by acetic acid.The Candida albicans of clinical strains were induced to apoptosis by using a weak acid acetic acid.The apoptosis was detected by flow cytometry and TEM. The data were processed for Chi-square test using SPSS11.5 software package.Oral Candida albicans had classic apoptosis when induced by proper concentration of acetic acid, and different concentrations of acetic acid had variable ability of inducing apoptosis of Candida albicans.Apoptosis can be detected in clinical strains of Candida albicans, the mechanism of apoptosis needs further research for the purpose of developing new antifungal drugs. Supported by National Natural Science Foundation of China(Grant No.30400498) and 2007 National College Student Innovative Planning Project.

Mono- and di-arginine conjugated PAMAM dendrimers (G = 3 or 4) were synthesized to examine the structure-activity relationships of arginine conjugation for gene delivery systems. Number of conjugated arginines was examined by 1H NMR (PAMAM3-R: 31, PAMAM4-R: 60, PAMAM3-R2: 59, PAMAM4-R2: 116). They could retard pDNA at a charge ratio of 2 and form polyplexes with sizes less than 250 nm from a charge ratio of 4. Di-arginine conjugated dendrimers showed higher Zeta-potential values and polyplex stabilities than mono-arginine conjugates. PAMAM3-R and PAMAM4-R showed low cytotoxicities even at high concentration but PAMAM3-R2 and PAMAM4-R2 exhibited significant cytotoxicities at high concentration. PAMAM3-R2 displayed greater transfection efficiency than PAMAM3-R, although the transfection efficiency of PAMAM4-R2 was not higher than that of PAMAM4-R in all condition. PAMAM3-R2 and PAMAM4-R2 polyplexes were observed to show the good intra-nuclear localization in comparison with PAMAM3-R and PAMAM4-R. It is concluded that di-arginine conjugation to PAMAM dendrimers can improve polyplex stability, intra-nuclear localization, and transfection efficiency but also induce charge density- and generation-dependent cytotoxicity. Therefore, a novel strategy for highly densed arginine conjugation maintaining low cytotoxicity will be needed for the development of efficient gene delivery carriers.

We synthesized arginine-conjugated polypropylenimine dendrimer G2 (DAB-8), PPI2-R for gene delivery systems. Synthesized PPI2-R could retard plasmid DNA at a weight ratio of 4 completely and PPI2-R polyplexes showed a fluorescence of less than 10% over a charge ratio of 2 by PicoGreen reagent assay, suggesting its good DNA condensing ability. The size of PPI2-R polyplex was measured to about 200nm at a charge ratio of 150. PPI2-R displayed 80-90% cell viability at even a 150microg/mL concentration. Transfection efficiency of PPI2-R was found to be high comparable to that of PEI25kD and to be 8-214 times higher than that of unmodified PPI2 on HeLa and 293 cells. Moreover, PPI2-R showed 4 times higher transfection efficiency than PEI25kD, treating with 10microg pDNA because of its low cytotoxicity on HeLa cells. Finally, PPI2-R showed a transfection efficiency 2-3 times higher than PEI25kD on HUVECs, showing its potency as a gene delivery carrier for primary cells. These results demonstrate that arginine-conjugation of PPI2 is successful in developing a low toxic and highly transfection efficient gene delivery carrier.

A clavicle fracture is a common traumatic injury. However, the high percentage of distal clavicle fractures associated with a rupture of the coracoclavicular (CC) ligament can result in delayed union or nonunion. There is no standard treatment for a clavicle fracture. This report introduces a method for treating distal clavicle fractures associated with a ruptured CC ligament using a cannulated screw.Seventeen patients suffering from a clavicle fracture caused by a rupture of the CC ligament were treated with a closed reduction and a cannulated screw fixation technique. Twelve patients were male and five were female and the average age was 30.5 years (range, 8-64 years). The patients were assessed using a clinical and radiologic evaluation as well as by the University of California at Los Angeles (UCLA) shoulder rating scale for 12 to 16 months after surgery.After confirming the formation of a callus, the implants were routinely removed approximately 8 weeks after surgery in all patients except for one. In this patient, the implant was removed 16 weeks after surgery as a result of a loosened screw, which caused displacement at the fracture site. During the final follow-up, the fracture site displayed nonunion and a partially limited range of motion (ROM). The shoulder function of the other 16 patients was restored to the preinjury level after 4 approximately 6 months of treatment. In one patient, heterotopic ossification was observed along the CC ligament without any functional deficit. All but one patient showed good results according to the UCLA scale.The cannulated screw fixation technique can maintain the rigid fixation of fracture fragments and allow an early return to work and sport activities. Therefore, the cannulated screw fixation technique is expected to be a useful method for treating distal clavicle fractures associated with a coracoclavicular ligament rupture.

Xanthogranulomatous epididymitis is an uncommon but benign process, characterized by tissue destruction and the accumulation of abundant foamy macrophages mixed with lymphocytes and plasma cells. The pathogens generally found to cause xanthogranulomatous inflammation have been Proteus and E. coli. We identified such a pathogen by sequencing divergent regions of 16S rRNA, followed by pathogen-specific-PCR using alr, ipaH, ial, and iuc primer pairs in DNA microdissected from an H&E stained slide. We report here three cases of xanthogranulomatous epididymitis caused by E. coli.

Reconstruction of the posterior cruciate ligament (PCL) has been performed in various ways. Recent biomechanical tests revealed that a double-bundle graft with a 2-tunnel technique is more likely to restore normal knee stability throughout the full range of knee motion. Several techniques using double-bundle grafts have been implemented for PCL reconstruction; however, each technique has its own advantages and disadvantages. To provide a simplified surgical technique and minimize its inherent complications, the purpose of this study was to introduce a novel technique of arthroscopic PCL reconstruction using an allogeneic tibialis anterior tendon and forming a single sling.

Background The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Methods Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, Results There was a significant correlation between Annexin A1 expression and pathologic differentiation grade (P=0.015) in OSCC patients. The proportion of patients with low Annexin A1 expression was significantly higher amongst those with moderate/poorly differentiated tumor (78/167) compared to those with well differentiated tumor (18/65). Multivariate Cox model analysis showed clinical stage (P=0.001) and Annexin A1 expression (P=0.038) as independent prognostic risk factors. Furthermore, a low Annexin A1 expression level was predictive of longer disease-free survival (P=0.036, HR=0.620) and locoregional recurrence-free survival (P=0.031, HR=0.607) compared to high Annexin A1 expression. Patients with moderate/poorly differentiated tumor and low Annexin A1 expression benefited from TPF induction chemotherapy as measured by distant metastasis-free survival (P=0.048, HR=0.373) as well as overall survival (P=0.078, HR=0.410). Conclusions Annexin A1 can be used as a prognostic biomarker for OSCC. Patients with moderate/poorly differentiated OSCC and low Annexin A1 expression can benefit from the addition of TPF induction chemotherapy to surgery and post-operative radiotherapy. Annexin A1 expression can potentially be used as a predictive biomarker to select OSCC patients with moderate/poorly differentiated tumor who may benefit from TPF induction chemotherapy.