The Treatment of Keloid Scars via Modulating Heterogeneous Gelatin-Structured Composite Microneedles to Control Transdermal Dual-Drug Release.

Keloid scarring is an abnormal scar disease characterised by excessive proliferation of fibroblasts and over-deposition of collagen during wound healing. Although various treatments for keloid scars have been developed, preventive medicine is believed to be a promising strategy. The skin barrier limits the gentle topical administration of medicaments such as creams and hydrogel dressings, resulting in reduced therapeutic efficacy. In recent years, microneedles (MNs) have been regarded as an appreciable device for topical administration without inducing side effects, and they are painless and do not cause bleeding. In this study, an MN patch with controlled transdermal dual-drug release was developed to achieve combinatory treatment of keloid scars using a heterogeneous gelatin-structured composite MN. Gelatin hydrogel was used as a substrate to load gallic acid (GA) and quercetin-loaded amphiphilic gelatin nanoparticles to fabricate dual-drug heterogeneous composite MNs. The results of the insertion test and mechanical properties of the MNs showed that the heterogeneous composite MN patches could be self-pressed into the stratum corneum and control dual-drug release at different time periods. GA was released at an earlier stage to retard the proliferation of fibroblasts, and quercetin was released at a later stage as a strong antioxidant to erase the generation of reactive oxygen species. Furthermore, real-time quantitative polymerase chain reaction data indicated that the gene expression of fibroblasts (such as Col I and III) was downregulated in the dual-drug system. The above results demonstrate that using heterogeneous composite MNs with the combination of dual-drug pharmacology is beneficial for preventing keloid scar formation.

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.

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.

[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.

Interleukin-1ß rs1143634 polymorphism and aggressive periodontitis susceptibility: a meta-analysis.

Multiple studies had focused on the association between interleukin-1 (IL-1) rs1143634 polymorphism and aggressive periodontitis (AgP) susceptibility, but the results remained inconclusive. Therefore, this meta-analysis was conducted to explore its role in the development of AgP. PubMed and Embase databases were searched up to April 15, 2014. After study selection and data extraction form eligible studies, meta-analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association. All the analysis was performed using Comprehensive Meta-Analysis software. Finally a total of 25 case-control studies were included. The pooled results showed non-association between AgP susceptibility and IL-1 rs1143634 polymorphism [for T vs. C: OR = 0.99, 95% CI = 0.79-1.23; for TT vs. CC: OR = 1.14, 95% CI = 0.78-1.66; for CT vs. CC: OR = 0.97, 95% CI = 0.70-1.36; for (CT + TT) vs. CC: OR = 1.02, 95% CI = 0.76-1.37; for TT vs. (CT + CC): OR = 1.22, 95% CI = 0.85-1.75]. Subgroup analyses remain did not find any association. No publication bias was detected. Hence, our meta-analysis showed that IL-1ß rs1143634 polymorphism is not linked to AgP susceptibility, regardless of ethnicity.

[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.

[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.