Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling.

Accumulating evidence has shown that fibromodulin (FMOD) plays a pivotal role in tumorigenesis and metastasis. However, the biological function of FMOD in oral squamous cell carcinoma (OSCC) remains largely unclear to date. In this study, we confirmed that FMOD was overexpressed and showed a significant association with malignant progression and lymph node metastasis in OSCC. Depletion of FMOD inhibited OSCC proliferation and metastasis in vitro and in vivo. RNA sequencing, western blotting, and rescue assays verified that FMOD exerted oncogenic roles in OSCC via activation of EGFR signaling. In addition, FMOD was proved to be a putative target gene of miR-338-3p. Taken together, FMOD overexpression due to the reduced level of miR-338-3p promotes OSCC by activating EGFR signaling. Our findings provide direct evidence that targeting FMOD could be a promising therapeutic strategy for OSCC patients.

A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2).

Background: Stanniocalcin-2 (STC2) is a secreted glycoprotein which plays an important role in regulating the homeostasis of calcium, glucose homeostasis, and phosphorus metastasis. Accumulating evidence suggests that STC2 is implicated in cancer mechanisms. However, the effects of STC2 on cancer development and progression across pan-cancer are not yet completely known. Methods: Data were downloaded from The Cancer Genome Atlas database to obtain differentially expressed genes significantly associated with prognosis (key genes). A gene was selected for subsequent correlation studies by integrating the significance of prognosis and the time-dependent ROC curve. Gene expression of different tumor types was analyzed based on the UCSC XENA website. Furthermore, our study investigated the correlation of STC2 expression between prognosis, immune cell infiltration, immune checkpoint genes (ICGs), mismatch repair genes (MMRs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity in various malignant tumors. Gene set enrichment analysis (GSEA) was conducted for correlated genes of STC2 to explore potential mechanisms. Results: A total of 3,429 differentially expressed genes and 397 prognosis-related genes were identified from the TCGA database. Twenty-six key genes were found by crossing the former and the latter, and the highest risk gene, STC2, was selected for subsequent correlation studies. STC2 had good diagnostic performance for HNSCC, and was closely related to the survival status and clinicopathological stage of HNSCC patients. In pan-cancer analysis, STC2 was upregulated in 20 cancers and downregulated in seven cancers. STC2 overexpression was overall negatively correlated with overall survival, disease-free survival, disease-specific survival, and progress-free survival. STC2 was profoundly correlated with the tumor immune microenvironment, including immune cell infiltration, ICGs, MMRs, TMB, and MSI. Moreover, STC2 was significantly negatively correlated with the sensitivity or resistance of multiple drugs. Conclusion: STC2 was a potential prognostic biomarker for pan-cancer and a new immunotherapy target.

Periodontitis Is Associated With Heart Failure: A Population-Based Study (NHANES III).

Objectives: The aim of this study was to investigate the relationship between periodontitis and heart failure using the Third National Health and Nutrition Examination Survey (NHANES III). Methods: Participants who had received a periodontal examination were included and investigated for the occurrence of heart failure. The included participants were divided into no/mild periodontitis and moderate/severe periodontitis groups according to their periodontal status. Weighted prevalence of heart failure was calculated, and weighted logistic regressions models were used to explore the association between periodontitis and heart failure. Possible influencing factors were then explored through subgroup analysis. Results: Compared with that of the no/mild periodontitis group, the incidence of heart failure in participants with moderate/severe periodontitis was 5.72 times higher (95% CI: 3.76-8.72, p < 0.001). After adjusting for gender, age, race, body mass index, poverty income ratio, education, marital status, smoking status, drinking status, hypertension, diabetes, stroke, and asthma, the results showed that the incidence of heart failure in the moderate/severe group was 3.03 times higher (95% CI: 1.29-7.13, p = 0.012). Subgroup analysis showed that criteria, namely, male, 40-60 years old, non-Hispanic white, body mass index >30, poverty income ratio ≥1, not more than 12 years of education, currently drinking, stroke but no diabetes, or asthma supported moderate/severe periodontitis as a risk factor for heart failure (p < 0.05). Conclusion: According to data from this nationally representative sample from the United States, periodontitis is associated with an increased risk of heart failure.

High-Density Horizontal Stacking of Chondrocytes via the Synergy of Biocompatible Magnetic Gelatin Nanocarriers and Internal Magnetic Navigation for Enhancing Cartilage Repair.

Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells. Here, we aimed to explore the repair effect of magnetized chondrocytes using magnetic amphiphilic-gelatin nanocarrier (MAGNC) to enhance cellular anchored efficiency and cellular magnetic guidance (MG) toward the superficial zone of damaged cartilage. The results of in vitro experiments showed that magnetized chondrocytes could be rapidly guided along the magnetic force line to form cellular amassment. Furthermore, the Arg-Gly-Asp (RGD) motif of gelatin in MAGNC could integrate the interaction among cells to form cellular stacking. In addition, MAGNCs upregulated the gene expression of collagen II (Col II), aggrecan, and downregulated that of collagen I (Col I) to reduce cell dedifferentiation. In animal models, the magnetized chondrocytes can be guided into the superficial zone with the interaction between the internal magnetic field and MAGNC to form cellular stacking. In vivo results showed that the intensity of N-sulfated-glycosaminoglycans (sGAG) and Col II in the group of magnetized cells with magnetic guiding was higher than that in the other groups. Furthermore, smooth closure of OA cartilage defects was observed in the superficial zone after 8 weeks of implantation. The study revealed the significant potential of MAGNC in promoting the high-density stacking of chondrocytes into the cartilage surface and retaining the biological functions of implanted chondrocytes for OA cartilage repair.

A smart injectable composite hydrogel with magnetic navigation and controlled glutathione release for promoting in situ chondrocyte array and self-healing in damaged cartilage tissue.

Injectable cell-based hydrogels allow surgical operation in a minimally invasive way for articular cartilage lesions but the chondrocytes in the injectable hydrogels are difficultly arrayed and fixed at the site of interest to repair the cartilage tissue. In this study, an injectable hyaluronic acid-polyacrylic acid (HA-pAA) hydrogel was first synthesized using hyaluronic acid-cyclodextrin (HA-CD) and polyacrylic acid-ferrocene (pAA-Fc) to provide cell-delivery and self-healing. To promote the cell fixation and alignment, porous poly(lactic-co-glycolic acid) (PLGA) magnetic microcapsules (PPMMs) with glutathione (GSH) loaded and iron oxide nanoparticles (IO) located in the shell were designed. The GSH-loaded PPMMs with layer-by-layer (LbL) assembly of hyaluronic acid (HA) and GSH (LbL-PPMMs) can provide a two-stage rapid and slow release of GSH to modulate the self-healing of the HA-pAA hydrogel at the injured site. Furthermore, the chondrocytes embedded in the HA-pAA hydrogel could be delivered through CD44 receptors on the HA polymer chains of LbL-PPMMs toward the surface of the damaged site by an internal magnetic force. The composite hydrogel system of chondrocytes/LbL-PPMMs/HA-pAA can provide the damaged cartilage with a more even and smooth surface than other groups in a rabbit model after 8 weeks of implantation. In addition, the chondrocytes in the deep zone tissue exhibit a columnar array, similar to the cell arrangement in normal cartilage tissue. Together with the cell navigation behavior and GSH release from the LbL-PPMM/HA-pAA hydrogel, a full closure of lesions on the cartilage tissue can be achieved. Our results demonstrate the highly promising potential of the injectable LbL-PPMM/HA-pAA system in cartilage tissue repair.

PEEK­biphasic bioceramic composites promote mandibular defect repair and upregulate BMP­2 expression in rabbits.

The present study aimed to investigate whether bone morphogenetic protein­2 (BMP­2) was involved in the repair of mandibular defects using polyether­ether­ketone biphasic bioceramic (PEEK­BBC) composites in rabbits. PEEK­BBC composites with abundant and interconnected pores were prepared by calcination and characterized by scanning electron microscope. A mandibular defect model in rabbits was established using dental grinder to produce a square hole. A total of 60 rabbits were divided into four groups: Control, sham, surgery, and PEEK. In the PEEK group, the holes were filled with the PEEK­BBC composite stents. In the surgery group, the holes were produced but not filled with the composite stents. In the sham group, only the molar grooves were exposed and grinding was not performed. Animals without any treatment served as the control group. The success rate of model establishment was 100%. At 4, 8, and 16 weeks after the model was established, samples were collected from the molding sites. Bone repair was evaluated by H&E staining and Goldner trichrome staining. Bone structures in both control and sham groups were intact. A small number of osteocytes were observed in the surgery group. However, in the PEEK group, osteocytes were already evidently present in the composites at 4 weeks after surgery. At 8 and 16 weeks, there were large numbers of osteocytes in the pores of the composites. The mRNA and protein expression levels of BMP­2 were determined by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The mRNA and protein expression levels of BMP­2 between the control and sham groups were similar and were continuously stable. However, following defect treatment, BMP­2 mRNA and protein expression was upregulated, which was enhanced by the PEEK­BBC composites. In conclusion, PEEK­BBC composites promoted the growth of osteocytes and repaired mandibular defects in rabbits, potentially via the upregulation of BMP­2 expression.

The augmented prophylactic antibiotic could be more efficacious in patients undergoing transrectal prostate biopsy: a systematic review and meta-analysis.

BACKGROUND: Although frequent use of prophylactic antibiotics for patients undergoing transrectal prostate biopsy (TRPB), incidences of urinary tract infection (UTI) and bacterial resistance are still increasing. We evaluated the efficacy of augmented prophylactic antibiotics in patients undergoing TRPB. METHODS: A systematic search of Embase(®), PubMed(®), and the Cochrane Library was executed to identify all eligible studies that compared the effects of augmented antibiotic prophylaxis (combined drugs) with single antibiotic prophylaxis on behalf of patients undergoing TRPB. Outcomes qualified in this review included bacteriuria, bacteremia, drug-resistant bacteria on urine culture, drug-resistant bacteria on blood culture, fever, UTI, sepsis, and hospitalization. RESULTS: A total of eight publications were identified and included in the review, including three randomized controlled trials with 659 patients and five case-control studies involving 3404 patients. All outcomes, including bacteriuria [relative risk (RR) 4.25, 95 % confidence interval (CI) 1.96-9.22, P = 0.0003], bacteremia (RR 4.96, 95 % CI 2.31-10.67, P < 0.0001), drug-resistant bacteriuria (RR 3.52, 95 % CI 1.41-8.78, P = 0.007), drug-resistant bacteremia (RR 4.94, 95 % CI 2.17-11.24, P = 0.0001), fever (RR 2.75, 95 % CI 1.63-4.62, P = 0.0001), UTI (RR 3.76, 95 % CI 2.57-5.48, P < 0.00001), and hospitalization (RR 3.90, 95 % CI 2.64-5.75, P < 0.00001) significantly favored the augmented antibiotic use. CONCLUSIONS: One additional type of antibiotic (usually one single dose) added to the basic antibiotic prophylaxis modality, defined as augmented prophylaxis, could contribute to the reduction in severe infection and drug resistance, particularly in high-risk patients.

Tumor necrosis factor-α G-308A (rs1800629) polymorphism and aggressive periodontitis susceptibility: a meta-analysis of 16 case-control studies.

Association between tumor necrosis factor-α (TNF-α) G-308A (rs1800629) polymorphism and susceptibility to aggressive periodontitis (AgP) were inconsistent, hence we performed this meta-analysis to clarify the association between them using Comprehensive Meta-Analysis v2.2 software. 16 case-control studies were searched from the PubMed, Embase and CNKI databases up to February 2, 2015. The meta-analysis showed a significantly increased risk in A vs. G (OR = 1.23, 95%CI = 1.04-1.44), AA vs. GG (OR = 2.07, 95%CI = 1.11-3.87), and AA vs. AG+GG genetic models (OR = 2.09, 95%CI = 1.13-3.86); however, the non-significantly increased risk was shown in AG vs. GG (OR = 1.06, 95%CI = 0.85-1.32) and AA+AG vs. GG genetic models (OR = 1.06, 95%CI = 0.85-1.31). Cumulative analysis showed that the association changed from non-significant to significant with new studies accumulated and the CIs became more and more narrow, sensitivity analysis indicated results were statistically robust. Stratified analyses of confirmed of HWE, Asians, Caucasians, and population-based controls obtained results similar to that of overall analysis. There was no evidence of publication bias. In summary, current evidence demonstrates that TNF-a G-308A polymorphism might be associated with AgP susceptibility, especially in Asians and Caucasians.

The Differential Expression and Function of the Inflammatory Chemokine Receptor CXCR5 in Benign Prostatic Hyperplasia and Prostate Cancer.

BACKGROUND: Chemokine and chemokine receptors could have played an important role in tumor angiogenesis and distant metastasis. The mechanism of inflammation, expression and function of chemokines and chemokine receptors in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remain unclear. The purpose of present study is to detect differential expression and function of chemokines and chemokine receptors (CCRs) in BPH and PCa. METHODS: BPH-1 and peripheral blood mononuclear cells (PBMCs) were co-cultured in Transwell chambers, and human normal prostate (NP) tissues, BPH tissues and PCa tissues were collected. CCR gene-chips were used to analyze and compare the differential expression of CCRs in BPH-1 cells, BPH-1 cells co-cultured with PBMCs, and LNCaP cells. The differential expression of CCRs was detected and validated using real-time PCR, western blotting and immunofluorescence (IF). The proliferation of LNCaP cells was also investigated after the knockdown CXCR5. RESULTS: RESULTS of gene-chips indicated that there was low or no expression of CCR10, CXCR1, CXCR3 and CXCR5 in BPH-1 cells, whereas the expression of these receptors in BPH-1 cells was increased by PBMCs, and the expression was high in LNCaP cells. Furthermore, real-time PCR and western blotting confirmed the above mentioned results. IF verified no or low expression of CXCR1, CXCR3 and CXCR5 in NP tissues, low or moderate expression in BPH and high expression in PCa. However, CCR10 was not expressed at detectable levels in the three groups. The growth and proliferation of LNCaP cells was markedly inhibited after down-regulation of CXCR5. CONCLUSIONS: PCa cells expressed high levels of CCR10, CXCR1, CXCR3 and CXCR5. Although BPH cells did not express these factors, their expression was up-regulated when BPH-1 cells were incubated with inflammatory cells. Finally, down-regulation of CXCR5 inhibited the growth and proliferation of LNCaP cells.

[Radical prostatectomy and radiation therapy for high-risk prostate cancer: An update].

Recently, the D'Amico classification system is widely used for the risk stratification of prostate cancer (PCa) , although no consensus has been reached for the definition of high-risk PCa. This system defines high-risk PCa as a prostate-specific antigen (PSA) level > 20 ng/ml, a Gleason score of 8-10, or a clinical stage ≥ T2c. Because high-risk PCa is prone to recurrence and metastasis after treatment, a proper initial therapy plays a crucial role. Currently, radical prostatectomy and radiation therapy are considered to be two most important options for the initial treatment of high-risk PCa although it remains controversial which is better.

Prophylactic Antibiotics in Prostate Biopsy: A Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: Despite frequent use of prophylactic antibiotics for patients undergoing transrectal prostate biopsy (TRPB), the incidences of urinary tract infection (UTI) and bacteria resistance are increasing. The aim of this study is to evaluate the current regimen of antimicrobial prophylaxis in TRPB. METHODS: A systematic search of PubMed(®), Embase(®), and the Cochrane Library was performed to identify all randomized controlled trials (RCT) related to the effects of antibiotic prophylaxis for TRPB. The outcomes included bacteriuria, bacteremia, drug-resistant bacteria on urine/blood culture, fever, UTI, sepsis, and hospitalization. RESULTS: A total of 22 RCTs with 3846 patients were identified and included. Nine trials analyzed antibiotics versus placebo/no treatment, with all outcomes substantially favoring antibiotic use (p<0.05), including bacteriuria (risk ratio [RR] 0.25, 95% confidence interval [CI] 0.15-0.42), bacteremia (RR 0.67, 95% CI 0.49-0.92), fever (RR 0.39, 95% CI 0.23-0.64), UTI (RR 0.37, 95% CI 0.22-0.62), and hospitalization (RR 0.13, 95% CI 0.03-0.55). There were no substantial differences between long-course versus short-course treatment and single versus multiple dose respectively, except for a greater risk of bacteriuria for short-course treatment (RR 2.09, 95% CI 1.17-3.73, p=0.01) and single-dose treatment (RR 1.98, 95% CI 1.18-3.33, p=0.01). There were no substantial differences among the groups for bacteriuria, fever, UTI, and hospitalization, when comparing oral versus systemic administration of antibiotics. The efficacy of several classes of antibiotics was compared without any difference among them. Despite the lack of significance, the synthesized data of three RCTs indicated a trend towards the use of combined antibiotics. CONCLUSIONS: Prophylactic antibiotics could be beneficial for the reduction of infective complications after TRPB. Single-dose or short-course oral administration with any type of antibiotic appears to be optimal. One additional type of antibiotic added to the basic antibiotic agent may contribute to the minimization of severe infection and drug resistance.

[Trans-lumbar-and-peritoneally joint approach for laparoscopic removal of large adrenal neoplasms].

OBJECTIVE: To explore the safety and efficacy of translumbar-and-peritoneally joint (TLPJ) approach for laparoscopic dissection of large neoplasms from adrenal glands. METHODS: Sixty patients with diameters > or = 6.0 cm adrenal neoplasms were recruited in this study. Of the participants, 30 were given transperitoneally laparoscopic adenectomy and 30 were given TLPJ approach. We compared the basic characteristics of the patients, as well as their conditions during and after operations. RESULTS: The two groups of patients had similar characteristics. No significant differences were found between the two approaches in terms of conversion to open surgery, estimated blood loss, transfusion, operating time, side injury, fluctuations of heart rate and blood pressure, and vascular accidents (P>0.05), although slight, but not significant, advantages were shown in the TLPJ patients on starting food intake and physical activities. Similar results were also found .in drainage volume, time to remove drainage, length of hospital stay, usage of analgesic, fever incidence, infection and intestinal obstruction etc (P>0.05). Above all, no significant differences were found between the two groups in recurrence, metastasis and overall survival rates (P>0.05). CONCLUSION: Laparoscopic surgery with TLPJ approach, translumbar combined with entirely side peritoneum opened, is safe and efficient compared with the traditional transperitoneal approach for patients with large adrenal neoplasms.

Antibiotics may not decrease prostate-specific antigen levels or prevent unnecessary prostate biopsy in patients with moderately increased prostate-specific antigen levels: A meta-analysis.

OBJECTIVES: To evaluate the effect of empiric antibiotics on decreasing prostate-specific antigen (PSA) levels and the possibility of avoiding unnecessary prostate biopsies (PBs). MATERIALS AND METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared effects of empiric antibiotics with no treatment or placebo on lowering PSA levels and minimizing unnecessary PBs in patients with moderately increased PSA levels. The Cochrane Collaboration Review Manager software (RevMan 5.1.4) was used for statistical analysis. RESULTS: The inclusion criteria for the study were met by 6 RCTs (1 placebo controlled and 5 no treatment controlled) involving 656 patients. The synthesized data from these RCTs indicated that there were no significant differences between the antibiotic and control groups in the PSA levels after treatment (mean difference [MD] = 0.15, 95% CI:-0.50 to 0.81, P = 0.65], number of patients with decreased PSA levels after treatment (relative risk [RR] = 1.22, 95% CI: 0.90-1.65, P = 0.20], prostate-specific antigen density levels after treatment (MD =-0.04, 95% CI:-0.15 to 0.07, P = 0.47), f/t% PSA after treatment (MD =-1.47, 95% CI:-4.65 to 1.71, P = 0.37), number of patients with responsive PSA (RR = 1.02, 95% CI: 0.58-1.81, P = 0.94), and individual Pca-positiverate in these patients (RR = 1.07, 95% CI: 0.53-2.16, P = 0.86), and Pca-positiverates (RR = 0.85, 95% CI: 0.48-1.50, P = 0.57). However, the antibiotic group had a significant change in the net PSA decrease after treatment compared with the control group (MD = 1.44, 95% CI: 0.70-2.17, P = 0.0001). CONCLUSION: The use of empiric antibiotics may not significantly decrease PSA levels or avoid unnecessary PBs.

[Circumcision with no-flip Shang Ring technique for adult males: analysis of 168 cases].

OBJECTIVE: To observe the clinical effects of the no-flip procedure with the Chinese Shang Ring when circumcising adult males with redundant prepuce or phimosis, and to discuss its advantages and disadvantages. METHODS: Using the no-flip Shang Ring technique, we performed circumcision for 167 adult males aged 18 -72 (mean 27.8) years with redundant prepuce or phimosis, and analyzed the clinical data, including the operation time, postoperative complications, ring-removal time, and postoperative appearance of the penis. RESULTS: Complete follow-up data of 94 cases (56.29%) were obtained. The mean operation time was (5.03 +/- 0.71) minutes and the average ring-removal time was (18.83 +/- 6.70) days. The primary postoperative complications were edema (35 cases [37.23%] at 2 weeks and 9 cases [9.57%] at 4 weeks), including 2 severe cases (2.13%), and infection (3 cases [3.19%]). The pain scores were 2.01 +/- 2.46 during the procedure and 4.52 +/- 2.53 at 24 hours postoperatively. Slipping of the outer ring occurred in 1 case, and delayed removal of the ring in 30 cases (31.91%). CONCLUSION: Adult male circumcision with the no-flip Shang Ring technique is recommended for its short operation time, simple procedure, fewer postoperative complications, less pain, and better incision appearance.

Cytochrome P450 2E1 RsaI/PstI polymorphism and risk of esophageal cancer: A meta-analysis of 17 case-control studies.

The aim of this study was to explore the cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and risk of esophageal cancer (EC) in mainland Chinese populations. A systematic search of PubMed, EMBASE, Web of Science, CBM, CNKI and VIP databases for publications on the CYP2E1 RsaI/PstI polymorphism and risk of EC was performed. and the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity and assessment of publication bias were performed. The search yielded 17 studies including 18 trails involving 1,663 cases and 2,603 controls. The meta-analyses showed a significant association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population (c2 vs. c1: OR=0.64; 95% CI, 0.50-0.81; P<0.001; c2/c2 vs. c1/c1: OR=0.73; 95% CI, 0.57-0.93; c2/c2 vs. c1/c1+c1/c2: OR=0.76; 95% CI, 0.60-0.96; P=0.02; c1/c2 vs. c1/c1: OR=0.54; 95% CI, 0.38-0.75; P<0.001; c1/c2+c2/c2 vs. c1/c1: OR=0.48; 95% CI, 0.34-0.70; P<0.001). An increased cancer risk in all genetic models was identified following stratification by ethnicity, source of controls and tumor type. In conclusion, in all genetic models, the association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population was significant. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism is a risk factor for EC, and the c2 allele is a factor that lowers the possibility of EC in the mainland Chinese population and this association did not change due to ethnic differences in genetic backgrounds and the environment.