Polymeric liposomes targeting dual transporters for highly efficient oral delivery of paclitaxel.

A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to enhance oral delivery of paclitaxel (PTX) by targeting monocarboxylate transporters (MCT) and glucose transporters (GLUT). The synthesized NSCF was characterised by FT-IR and 1H NMR spectra. The prepared 30.78 % (degree of substitution of N-SAA) NSCF-PTX-PLip were approximately 150 nm in size, with a regular spherical shape, the zeta potential of -25.4 ± 5.13 mv, drug loading of 2.35 % ± 0.05 %, and pH-sensitive and slow-release characteristics. Compared with PTX-Lip, 30.78 % NSCF-PTX-PLip significantly enhanced Caco-2 cellular uptake via co-mediation of MCT and GLUT, showing relatively specific binding of propionic acid and MCT. Notably, the NSCF modification of PTX-Lip had no appreciable influence on their original cellular uptake pathway. The fructose modification of 30.78 % NSC-PTX-PLip significantly increased the concentration after tmax, indicating their continuous and efficient absorption. Compared with PTX-Lip, the 30.78 % NSCF-PTX-PLip resulted in a 2.09-fold extension of MRT, and a 6.06-fold increase of oral bioavailability. It significantly increased tumour drug distribution and tumour growth inhibition rate. These findings confirm that 30.78 % NSCF-PLip offer a potential oral delivery platform for PTX and targeting the dual transporters of MCT and GLUT is an effective strategy for enhancing the intestinal absorption of drugs.

Highly efficient removal of Cr(VI) from wastewater using electronegative SA/EGCG@Ti/SA/PVDF sandwich membrane.

The use of green, non-toxic raw materials is of great significance to the sustainable development of the environment, among which epigallocatechin gallate (EGCG) is a renewable carbon source from plants. At present, there is a lack of research on the metal-polyphenol nanomaterials their use in water decontamination. In this study, a novel SA/EGCG@Ti/SA/PVDF (SESP) sandwich membrane was prepared to effectively solve the problems of difficult recovery of nanomaterials and the leaching of metal ions. The membrane was made by scraping SA on the surface of the PVDF substrate as the bottom protective layer, depositing EGCG@Ti NPs as the functional layer, then coating SA as the surface isolation layer, and finally cross-linking with anhydrous calcium chloride. Results showed that EGCG@Ti NPs dispersed well on the surface of the SA/PVDF basement membrane. SESP sandwich membrane had good hydrothermal and acid-base stability, and it can be applied to wastewater with multiple co-existing heavy metals (e.g., Cu, Pb, Cd, and Ni). The contact angle and pure water flux of the SESP sandwich membrane with a negatively charged surface were 14.0-15.6° and 171.40 L/m2 h, respectively. The pure water flux of the regenerated membrane after BSA pollution recovered to 98.68 L/m2 h, and the interception efficiency and the interception flux of Cr(VI) were 100 % and 72.92 L/m2 h at 40 min of interception, respectively. Additionally, the removal efficiency of Cr(VI) by SESP sandwich membrane was maintained above 83 % for simulated wastewater and 100 % for actual wastewater after five adsorption-desorption cycles. Cr(VI) and Cr(III) can be removed simultaneously with the negatively charged SESP sandwich membrane. EDS and XPS analysis showed that the removal of Cr(VI) was controlled by the Donnan effect, anion exchange, chelation/complexation, and reduction mechanism. In contrast, Cr(III) was mainly influenced by electrostatic attraction and chelation/complexation mechanisms. In conclusion, the newly prepared sandwich membrane has good application potential in treating Cr(VI) wastewater.

Fatty hepatocytes-derived exosomal miR-122 reduces immune function and antioxidant defence in Ctenopharyngodon idella kidney (CIK) cells.

Exosomes are important for intercellular "cross talk", but the role of exosomes in communication between hepatocytes and C. idella kidney (CIK) cells remains unknown. In this study, we detected the changes in factors related to immune and oxidative stress to investigate the molecular mechanism by which fatty hepatocyte-derived exosomes (OA-Exos) reduced immunity and induced oxidative stress in CIK cells. After incubation of CIK cells by OA-Exos for 24 h, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and interleukin-1ß (IL-1ß) were significantly upregulated in the OA-Exos group (P < 0.05), and Mn superoxide dismutase (Mn-SOD) and heme oxygenase-1 (HO-1) were significantly downregulated (P < 0.05). Surprisingly, miR-122 expression was also significantly elevated after OA-Exos incubation. We further identified the expression of miR-122 and found that it was notably increased in OA-Exos compared to hepatocyte-derived exosomes (Exos). Then we transfected CIK cells with miR-122 mimic, consistently, the expression of inflammatory cytokines was also significantly elevated (P < 0.05), and the expression of glutathione peroxidase (GPx), HO-1, and Mn-SOD were dramatically decreased (P < 0.05). Furthermore, HO-1 was improved to be a direct target of miR-122, and transfection with HO-1 siRNA indicated that changes in inflammatory cytokines and genes related to oxidative stress were consistent with the above results of CIK cells incubated with OA-Exos and miR-122 mimic. We concluded that OA-Exos may, through the miR-122/HO-1 pathway, reduce immune function and antioxidant defence in CIK cells.

Distinct responses from triglyceride and cholesterol metabolism in common carp (Cyprinus carpio) upon environmental cadmium exposure.

Due to high persistence and bioavailability, Cadmium (Cd) is one of the most prevalent environmental contaminants, posing an elevating threat to the ecosystems. It has been evidenced that high-dose Cd elicits deleterious effects on aquatic organisms, but the potential toxicities of Cd at environmentally relevant concentrations remains underappreciated. In this study, we used common carp to investigate how environmental Cd exposure affects triglyceride (TG) and cholesterol metabolism and underlying mechanisms. The data indicated that Cd resulted in the shift of TG from the liver to blood and the movement of cholesterol in the opposite direction, ultimately giving rise to the storage of crude lipid in liver and muscle, especially hepatic cholesterol retention. Cholesterol, instead of TG, became the principal cause during the progression of hepatic lipid accumulation. Mechanistic investigations at transcriptional and translational levels further substantiated that Cd blocked hepatic biosynthesis of TG and enhanced TG efflux out of the liver and fatty acid ß-oxidation, which collectively led to the compromised TG metabolism in the liver and accelerated TG export to the serum. Additionally, strengthened synthesis, retarded export and oxidation of cholesterol detailed the hepatic prominent cholesterol retention. Taken together, our results demonstrated that environmental exposure to Cd perturbed lipid metabolism through triggering distinct responses from hepatic TG and cholesterol homeostasis. These indicated that environmental factors (such as waterborne Cd) could be a potential contributor to the prevalence of non-alcoholic fatty-liver disease in aquaculture and more efforts should be devoted to the ecological risk assessment of pollutants under environmental scenarios.

Long intergenic non-protein coding RNA 115 (LINC00115) aggravates retinoblastoma progression by targeting microRNA miR-489-3p that downregulates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2).

Long non-coding RNAs (lncRNAs) are key regulators of cancer. However, the role of long intergenic non-protein coding RNA 115 (LINC00115) in the regulation of retinoblastoma (RB) has not yet been studied. The expression levels of LINC00115, microRNA (miR)-489-3p, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) in RB tissues or cells were detected by quantitative reverse transcription-polymerase chain reaction. The proliferation and migration of cells were detected by the cell counting kit-8 and Transwell assays. Luciferase reporter gene analysis and RNA immunoprecipitation assay were used to validate the target gene interactions predicted by starBase. A xenograft tumor experiment was conducted to validate the in vivo outcomes. The expression levels of LINC00115 and PFKFB2 in RB tissues were higher than those in normal tissues, while miR-489-3p showed the opposite trend. Silencing of LINC00115 inhibited the proliferation and migration of SO-RB50 and HXO-RB44 cells. An inhibitory or facilitated effect on RB tumorigenesis was observed following PFKFB2 silencing or miR-489-3p overexpression, respectively. Moreover, LINC00115 aggravated RB progression by targeting miR-489-3p, which downregulated PFKFB2. This finding improves our understanding of the relationship between LINC00115 and RB. Furthermore, miR-489-3p and PFKFB2 may be used as potential targets for RB prevention and treatment.

Bupleurum chinense DC improves CUMS-induced depressive symptoms in rats through upregulation of the cAMP/PKA/CREB signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC. (B. chinense) is the dried root of B. chinense, belonging to the Umbelliferae family. B. chinense has been reported since ancient times for its effect of soothing the liver and relieving depression. Additionally, its important role in treating depression, depressed mood disorders and anti-inflammation has been proven in previous studies. However, its specific mechanism of action remains unknown. AIM OF THE STUDY: The key targets and metabolites of the antidepressant effect of B. chinense were investigated based on the cAMP signalling pathway. The study examined the mechanism for the antidepressant effect of B. chinense by target prediction, analysis of related metabolites and potential metabolic pathways. MATERIALS AND METHODS: A network pharmacology approach was used to predict the antidepressant targets and pathways of B. chinense. A depression rat model was established through the CUMS (chronic unpredictable mild stress) procedure. The depression model was assessed by body weight, sugar-water preference, water maze and enzyme-linked immunosorbent assay (ELISA) indicators (5hydroxytryptamine, etc.). The key metabolic pathways were screened by correlations between metabolites and key targets. Finally, a quantitative analysis of key targets and metabolites was experimentally validated. RESULTS: B. chinense significantly ameliorated the reduction in body weight, sugar-water preference rate and cognitive performance in the water maze experiment in rats with depression induced by CUMS. ELISA, Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) assays showed that B. chinense significantly improves the expression of protein kinase cyclic adenylic acid (cAMP)-activated catalytic subunit alpha (PRKACA), cAMP-response element-binding protein (CREB) and cAMP activation in the rat brain induced by CUMS. According to metabolic pathway analysis, B. chinense shows an antidepressant effect primarily by regulating the cAMP metabolic pathway. CONCLUSION: B. chinense upregulated PRKACA and CREB expression and the level of the key metabolite cAMP in the cAMP/PKA/CREB pathway while reducing the inflammatory response to depression treatment. These new findings support future research on the antidepressant effects of B. chinense.

Predictive Risk Factors of the Conversion from Video-Assisted Treatment of Anal Fistula to Seton Fistulotomy.

Background: To identify the risk factors of converting from video-assisted anal fistula treatment (VAAFT) to seton fistulotomy. Materials and Methods: A total of 180 patients registered to undergo VAAFT between January 2016 and June 2020 at the Erlonglu Hospital. Intraoperative examination of the fistula tract revealed that the patients were assigned to undergo the VAAFT operation and seton fistulotomy. Results: Among 180 patients aged 37 (±10.4) years who underwent intraoperative examination of the fistula tract, 101 completed the standard VAAFT and 79 converted to seton fistulotomy. Univariate analyses revealed that age, necrotic cavity diameter ≥1 cm, scars at the anal entrance, tissue edema, Parks classification, fistula stenosis, and fistula branches were significantly different between the VAAFT and converted groups (P < .05). Multivariate analysis revealed a significant correlation between the risk of surgery conversion and the presence of necrotic cavity with a diameter of ≥1 cm (odds ratio [OR]: 3.668, 95% confidence interval [CI]: 1.366-9.853, P = .01), scars at the anal entrance (OR: 9.462, 95% CI: 1.562-57.32, P = .014), fistula stenosis (OR: 25.14, 95% CI: 5.211-121.3, P < .001), and fistula branches (OR: 2.90, 95% CI: 1.088-7.73, P = .033). The nomogram based on the logistic model was fitted with high accuracy and area under curve of 0.793 (95% CI: 0.726-0.861). Conclusions: The independent risk factors of conversion from surgery for VAAFT to seton fistulotomy were the presence of necrotic cavity with a diameter of ≥1 cm, scars at the anal entrance, fistula stenosis, and fistula branches. The protocol of this systematic review was registered a priori in the Chinese Clinical Trial Registry (ChiCTR) under the registration number of ChiCTR1900022810.

Predicting the herbal medicine triggering innate anti-tumor immunity from a system pharmacology perspective.

Although the main focus of immuno-oncology has been manipulating the adaptive immune system, tumor associated macrophages (TAMs) are the main infiltrating component in the tumor microenvironment (TME) and play a critical role in cancer progression. TAMs are mainly divided into two different subtypes: macrophages with antitumor or killing activity are called M1 while tumor-promoting or healing macrophages are named M2. Therefore, controlling the polarization of TAMs is an important strategy for cancer treatment, but there is no particularly effective means to regulate the polarization process. Here, combined systems pharmacology targets and pathways analysis strategy, we uncovered Scutellariae Radix (SR) has the potential to regulate TAMs polarization to inhibit the growth of non-small cell lung cancer (NSCLC). Firstly, systems pharmacology approach was used to reveal the active components of SR targeting macrophages in TME through compound target prediction and target-microenvironment phenotypic association analysis. Secondly, in vitro experiment verified that WBB (wogonin, baicalein and baicalin), major active ingredients of SR are significantly related to macrophages and survival, initiated macrophages programming to M1-like macrophages to promoted the apoptosis of tumor cells. Finally, we evidenced that WBB effectively inhibited tumor growth in LLC (Lewis lung carcinoma) tumor-bearing mice and increased the infiltration of M1-type macrophages in TME. Overall, the systems pharmacology strategy offers a paradigm to understand the mechanism of polypharmacology of natural products targeting TME.

Poria cum Radix Pini Rescues Barium Chloride-Induced Arrhythmia by Regulating the cGMP-PKG Signalling Pathway Involving ADORA1 in Zebrafish.

The traditional Chinese medicine Poria cum Radix Pini (PRP) is a fungal medicinal material that has been proven to play an important role in the treatment of arrhythmia. However, the mechanism of its effect on arrhythmia is still unclear. In this study, network pharmacology and metabolomics correlation analysis methods were used to determine the key targets, metabolites and potential pathways involved in the effects of PRP on arrhythmia. The results showed that PRP can significantly improve cardiac congestion, shorten the SV-BA interval and reduce the apoptosis of myocardial cells induced by barium chloride in zebrafish. By upregulating the expression of the ADORA1 protein and the levels of adenosine and cGMP metabolites in the cGMP-PKG signalling pathway, PRP can participate in ameliorating arrhythmia. Therefore, we believe that PRP shows great potential for the treatment of arrhythmia.

Effects of Tamoxifen vs. Toremifene on fatty liver development and lipid profiles in breast Cancer.

BACKGROUND: Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. However, TAM has been proved to affect serum lipid profiles and cause fatty liver disease. The study aimed to compare the effects of TAM and TOR on fatty liver development and lipid profiles. METHODS: This study performed a retrospective analysis of 308 SERMs-treated early breast cancer patients who were matched 1:1 based on propensity scores. The follow-up period was 3 years. The primary outcomes were fatty liver detected by ultrasonography or computed tomography (CT), variation in fibrosis indexes, and serum lipid profiles change. RESULTS: The cumulative incidence rate of new-onset fatty liver was higher in the TAM group than in the TOR group (113.2 vs. 67.2 per 1000 person-years, p < 0.001), and more severe fatty livers occurred in the TAM group (25.5 vs. 7.5 per 1000 person-years, p = 0.003). According to the Kaplan-Meier curves, TAM significantly increased the risk of new-onset fatty liver (25.97% vs. 17.53%, p = 0.0243) and the severe fatty liver (5.84% vs. 1.95%, p = 0.0429). TOR decreased the risk of new-onset fatty liver by 45% (hazard ratio = 0.55, p = 0.020) and showed lower fibrotic burden, independent of obesity, lipid, and liver enzyme levels. TOR increased triglycerides less than TAM, and TOR increased high-density lipoprotein cholesterol, while TAM did the opposite. No significant differences in total cholesterol and low-density lipoprotein cholesterol are observed between the two groups. CONCLUSIONS: TAM treatment is significantly associated with more severe fatty liver disease and liver fibrosis, while TOR is associated with an overall improvement in lipid profiles, which supports continuous monitoring of liver imaging and serum lipid levels during SERM treatment.

Treatment of Complex Anal Fistula by Video-Assisted Anal Fistula Treatment Combined with Anal Fistula Plug: A Single-Center Study.

Objective. The surgical treatment of complex anal fistulae is very challenging because of the incidence of incontinence after traditional approaches. There are no studies on the role of video-assisted anal fistula treatment (VAAFT) combined with anal fistula plug (AFP) in the complex anal fistulae. The aim of this study was to demonstrate the efficacy of treating complex anal fistulae using VAAFT combined with AFP. Method. This was a retrospective, nonrandomized observational study. 57 consecutive patients with complex anal fistulae who had undergone the VAAFT with AFP in our hospital between April 2016 and December 2019 were included. The primary outcomes were the cure rate, recurrence rate, and Wexner incontinence scores; the secondary outcomes were surgery time, blood loss, wound healing time postoperatively, pain, and patient satisfaction. Results. All 57 patients completed the surgery and follow-up, with an average follow-up time of 28 months; 6 patients suffered with recurrence (recurrence rate: 10.5%). The average surgery time was 57.9 minutes, and the average wound healing time was 46 days. There were no severe postoperative complications, and anal sphincter function was protected in all patients. Conclusions. The treatment of complex anal fistula by VAAFT combined with AFP is safe and effective, has a high healing rate and few postoperative complications, and is a promising surgery that can effectively protect the patient's anal sphincter function.

Video-assisted anal fistula treatment combined with anal fistula plug for treatment of horseshoe anal fistula.

OBJECTIVE: Horseshoe anal fistula is a common anorectal disease, and there is no standard procedure for its treatment. In this study, we performed a modified surgical procedure for the treatment of horseshoe anal fistula and investigated its efficacy and adverse effects. METHODS: We retrospectively analyzed the outcomes of video-assisted anal fistula treatment combined with an anal fistula plug (VAAFT-Plug) in 26 patients with a horseshoe anal fistula. The follow-up period ranged from 6 to 18 months. Preoperative and postoperative data were collected to analyze the cure rate, anal sphincter function, and incidence of complications. RESULTS: The surgeries were successfully performed in all patients, 23 of whom were cured (effective cure rate of 88.46%). Three patients developed recurrence and were cured after traditional surgery. No patients developed severe complications or postoperative anal incontinence. The VAAFT-Plug protocol was performed with a small incision in the fistula that subsequently promoted fistula healing and preserved sphincter function. CONCLUSION: Although randomized controlled trials will be needed to fully validate these findings, our results suggest that VAAFT-Plug represents a promising treatment strategy for horseshoe anal fistulas. This technique preserves normal anal function and achieves satisfactory outcomes in most patients.

Transcriptome analysis of common carp (Cyprinus carpio) provides insights into the ovarian maturation related genes and pathways in response to LHRH-A and dopamine inhibitors induction.

Luteinizing hormone-releasing hormone analog (LHRH-A) and dopamine inhibitors have been widely used to induce oocyte maturation and ovulation in domesticated fishes. Although this approach represents a reliable method for regulating fish reproduction, the underlying molecular mechanisms mediating LH action are largely unexplored. The objective of this study was to determine the transcriptional profile of gene programming in hormone-treated common carp. In the present study, female common carp were intraperitoneally injected with LHRH-A together with dopamine inhibitors, and control fish were injected with saline. Ovarian morphological changes were analysed by both light microscopy and scanning electron microscopy. Furthermore, gene expression profiling of the brain and ovarian tissues was performed by Illumina sequencing. Compared to the control carp, hormone treatment resulted in morphological changes including disappearance of nuclear membrane, breakdown of germinal vesicle (GVBD), and fusion of yolk globules, reflecting that hormones significantly promoted oocyte maturation. In comparison to control, we have identified 867 and 9,053 differentially expressed genes in the hormone-treated female brain and ovary, respectively. In the brain, most of the identified genes were significantly enriched in 18 KEGG pathways. In the ovarian tissue, the identified genes were significantly involved in 9 pathways. In the hormone-treated carp, genes were involved in calcium signalling pathway, cAMP signalling pathway, insulin secretion, and oxidative phosphorylation pathway, which showed obvious associations with ovarian maturation. The present study provides transcriptomic information for hormone-treated carp, which might be useful for studying the endocrine regulation and mechanisms of ovarian maturation in domesticated fishes.

Haptic Rendering of Diverse Tool-Tissue Contact Constraints During Dental Implantation Procedures.

Motor skill learning of dental implantation surgery is difficult for novices because it involves fine manipulation of different dental tools to fulfill a strictly pre-defined procedure. Haptics-enabled virtual reality training systems provide a promising tool for surgical skill learning. In this paper, we introduce a haptic rendering algorithm for simulating diverse tool-tissue contact constraints during dental implantation. Motion forms of an implant tool can be summarized as the high degree of freedom (H-DoF) motion and the low degree of freedom (L-DoF) motion. During the H-DoF state, the tool can move freely on bone surface and in free space with 6 DoF. While during the L-DoF state, the motion degrees are restrained due to the constraints imposed by the implant bed. We propose a state switching framework to simplify the simulation workload by rendering the H-DoF motion state and the L-DoF motion state separately, and seamless switch between the two states by defining an implant criteria as the switching judgment. We also propose the virtual constraint method to render the L-DoF motion, which are different from ordinary drilling procedures as the tools should obey different axial constraint forms including sliding, drilling, screwing and perforating. The virtual constraint method shows efficiency and accuracy in adapting to different kinds of constraint forms, and consists of three core steps, including defining the movement axis, projecting the configuration difference, and deriving the movement control ratio. The H-DoF motion on bone surface and in free space is simulated through the previously proposed virtual coupling method. Experimental results illustrated that the proposed method could simulate the 16 different phases of the complete implant procedures of the Straumann® Bone Level(BL) Implants Φ4.8-L12 mm. According to the output force curve, different contact constraints could be rendered with steady and continuous output force during the operation procedures.

Elevation of S100 calcium-binding protein A7 in recurrent pterygium.

Recurrent pterygium, a common ophthalmic disease, is difficult to treat as its pathogenesis is unclear. To investigate the key genes responsible for the recurrence of pterygium, tissue samples were collected from six patients with primary pterygium (primary group), six patients with recurrent pterygium (recurrent group) and six patients with ocular trauma (control group) who underwent surgery between December 2014 and June 2017. The differentially expressed genes amongst these tissues were detected using expression profiling microarrays and verified by reverse transcription-quantitative PCR (RT-qPCR). Comparing the primary and control groups, 10 genes, including PP7080, small proline-rich protein 2A, keratin 24, small proline-rich protein 2F, defensin ß4A, serpin family A member 3, S100 calcium-binding protein A7 (S100A7), Fc fragment of IgG binding protein and BPI Fold Containing Family A Member 1, were identified to be consistently upregulated in recurrent pterygium tissues, whilst two genes (H19 imprinted maternally expressed transcript and secretoglobin family 2A member 1) were consistently downregulated. Following RT-qPCR verification, it was identified that that S100A7 gene was significantly upregulated in recurrent pterygium tissues compared with the other groups. Protein-protein interaction and Gene Ontology analysis further revealed that all genes interacting with S100A7 were mainly involved in the regulation of defense mechanisms against bacteria, mitogen-activated protein kinase (MAPK) pathway activation and receptor for advanced glycation end-products receptor binding. The present findings confirmed that elevation of S100A7 expression in recurrent pterygium may be associated with the inflammatory response and activation of the MAPK signaling pathway.

Rectal inclusion cyst as a complication of stapled hemorrhoidopexy: A case report.

RATIONALE: Stapled hemorrhoidopexy is gaining popularity for prolapsing hemorrhoids. However, like any other operation, there is always the potential risk of complications. Rectal inclusion cysts are rare complications that results from the potential space in the staple line. PATIENT CONCERNS: A 49-year-old woman was admitted to our hospital with a complaint of anorectal pain and fever complaints after stapled hemorrhoidopexy. The endoanal ultrasonography showed unclear fluid containing a cystic lesion circuit to the rectum at the staple line. DIAGNOSES: The endoanal ultrasonography strongly indicates the rectal inclusion cysts. INTERVENTIONS AND OUTCOMES: A full thickness excision of the cyst was carried out along the staple line. The patient had complete recovery, with no recurrence or complaints for at least 6 months after the surgery. LESSONS: Endosonography has an important role in investigating symptomatic patients after stapled hemorrhoidopexy. Once an inclusion cyst is diagnosed, excision of the stapled line is the only choice of treatment.

[The effect of GDNF on matrix-degrading and cell-adhesion during perineural invasion of salivary adenoid cystic carcinoma].

PURPOSE: To investigate the possible contribution of GDNF in matrix-degrading, cell-adhesion during perineural invasion (PNI) of salivary adenoid cystic carcinoma (ACC). METHODS: Totally 42 ACCs and 5 normal salivary tissues were included in the present study．Immunohistochemical staining SP method was used to detect the expression of GDNF,MMP-9,NF-κB,integrin ß1 in ACC specimens and normal salivary tissues. Statistical analysis was performed using SPSS16.0 software package. RESULTS：GDNF was strongly expressed in ACC tumor cells and nerve fibers adjacent to ACC tumor cells. NF-κB, MMP-9, integrin ß1 were positively expressed in ACC cell cytoplasm, integrin ß1 was also found in ACC cell membrane, and NF-κB in nuclei occasionally. The positive expression rate was 69.05%（29/42）,66.67%（28/42）,61.90%（26/42）, respectively. The differences between the expression of NF-κB, MMP-9, integrinß1 in PNI group and non-PNI group were significant (P=0.005,P=0.011,P=0.001, respectively). Expression of NF-κB, MMP-9, integrin ß1 was correlated to that of GDNF(r=0.443, P=0.003; r=0.401, P=0.009; r=0.535, P=0.000, respectively). Expression of MMP-9 and integrin ß1 was positively correlated to that of NF-κB(r=0.501, P=0.001; r=0.429, P=0.005). Expression of MMP-9 was correlated positively to that of integrin ß1 (r=0.381, P=0.013). CONCLUSIONS：GDNF may increase the matrix-degrading and cell-adhesion of ACC in the process of PNI. NF-κB, MMP-9 and integrin ß1 involve in ACC cells invading nerves.

Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans.

The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.

Preliminary evaluation of a virtual reality dental simulation system on drilling operation.

To evaluate the fidelity of the iDental system and investigate its utility and performance on simulated drilling operations, user studies consisting of objective and subjective evaluations were performed. A voxel-based drilling simulation sub-system in the iDental system was employed for evaluation. Twenty participants were enrolled to take part in the experiments and were divided into two groups: novice and resident. A combined evaluation method including objective and subjective methods was employed. The objective evaluation included two dental drilling tasks: caries removal operation and pulp chamber opening operation. In the subjective method, participants were required to complete a questionnaire to evaluate the fidelity of the system after the operation task. Based on the structured global assessment scales in the questionnaire, the average subjective evaluation scores of the proposed metrics were greater than 4.5, demonstrating that the system operated above medium fidelity. Dentists expressed great interest and positive attitudes toward the potential of the iDental system. The objective evaluation data including time spent and the volume of removed healthy and carious tissue were obtained. Although no significant differences could be found between the two groups, the volume of removed caries and the depth of pulp chamber insertion manifested small standard deviations. Evaluation results illustrated that dentists were willing to use the virtual reality training system. Several future research topics were identified, including increasing the task difficulty, improving the system fidelity and introducing appropriate finger rest points.