Mulberry Leaf Lipid Nanoparticles: a Naturally Targeted CRISPR/Cas9 Oral Delivery Platform for Alleviation of Colon Diseases.

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

Simultaneous Detection of Two Extracellular Vesicle Subpopulations in Saliva Assisting Tumor T Staging of Oral Squamous Cell Carcinoma.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Ultraviolet Light Responsive N-Nitroso Polymers for Antibacterial Nitric Oxide Delivery.

This study investigates the incorporation of active secondary amine moieties into the polymer backbone by co-polymerizing 2,4,6-tris(chloromethyl)-mesitylene with three diamines, namely 1,4-diaminobutane, m-phenylenediamine, and p-phenylenediamine. This process results in the stabilization of the amine moieties and the subsequently introduced nitroso groups. Charging bioactive nitric oxide (NO) into the polymers is accomplished by converting the amine moieties into N-nitroso groups. The ability of the polymers to store and release NO depends on their structures, particularly the amount of incorporated active secondary amines. With grafting photosensitive N-nitroso groups into the polymers, the derived NO@polymers exhibit photoresponsivity. NO release is completely regulated by adjusting UV light irradiation. These resulting polymeric NO donors demonstrate remarkable bactericidal and bacteriostatic activity, effectively eradicating E. coli bacteria and inhibiting their growth. The findings from this study hold promising implications for combining NO delivery with phototherapy in various medical applications.

Effect of platelet-rich plasma on the attachment of periodontal ligament fibroblasts to the diseased root surface and the attendant collagen formation.

OBJECTIVE: To investigate the effect of different concentrations of platelet-rich plasma (PRP) on collagen formation via periodontal ligament fibroblasts (PDLFs) on the surface of demineralised diseased tooth roots. METHODS: Various PDLFs were grown from tissue explants, with the cells between the fifth and eighth passage in the culture used. Human whole blood obtained from healthy subjects was collected in tubes containing an anticoagulant (acid-citrate-dextrose) and centrifuged (1300 rpm for 10 min) before the supernatant PRP layer was removed. A second spin at (2000 rpm for 10 min) produced the PRP fraction. The effect of PRP of various concentrations on the attachment of PDLFs on the diseased root surface of human teeth demineralised with ethylenediaminetetraacetic acid (EDTA) and treated with the PRP was then investigated in terms of PRP collagen formation, with the formation observed using the Sirius red staining method. RESULTS: The optical density values of the experimental groups were statistically significantly higher than those of the control groups (P < 0.05), while the Sirius red staining returned positive results for both the experimental group (A) and the control group (B). The images were analysed using a histogram, and a statistically significant difference was found (P < 0.05). CONCLUSION: While PRP could promote the attachment and collagen formation of PDLFs on the diseased root surface of human teeth demineralised with EDTA and treated with PRP, the effect is potentially reduced when the dose exceeds 20%.

Enhanced antitumour efficiency of R8GD-modified epirubicin plus tetrandrine liposomes in treatment of gastric cancer via inhibiting tumour metastasis.

Tumour metastasis is a major cause of cancer treatment failure and death, and chemotherapy efficiency for gastric cancer patients is usually unsatisfactory due to tumour cell metastasis, poor targeting and serious adverse reactions. In this study, a kind of R8GD-modified epirubicin plus tetrandrine liposomes was prepared to enhance the antitumor efficiency via killing tumour cells, destroying tumour metastasis and inhibiting energy supply for tumour cells. In order to investigate the antitumour efficiency of the targeting liposomes, morphology observation, intracellular uptake, cytotoxic effects, and inhibition on tumour metastasis and energy supply were carried out in vitro, and tumour-bearing mice models were established to investigate the antitumour efficiency in vivo. In vitro results showed that R8GD-modified epirubicin plus tetrandrine liposomes with ideal physicochemical properties could kill the most tumour cells, inhibit tumour metastasis and cut-off energy supply for tumour cells. In vivo results exhibited that R8GD-modified epirubicin plus tetrandrine liposomes could enhance the accumulation in tumour site and display an obvious antitumor efficiency. Therefore, R8GD-modified epirubicin plus tetrandrine liposomes could be used as a potential therapy for treatment of gastric cancer.

Comparison of endoscopic bilateral metal stent drainage with plastic stents in the palliation of unresectable hilar biliary malignant strictures: Large multicenter study.

BACKGROUND: Endoscopic stenting to manage malignant hilar biliary obstruction has no consensus regarding the optimal stenting strategy. In this multicenter study, we compared transpapillary parallel-style bilateral metal stenting with bilateral plastic stenting, and evaluated short- and long-term outcomes. METHODS: We recruited 262 consecutive patients (Bismuth classification types II-IV) who underwent either bilateral metal or plastic stenting as primary therapy at four tertiary centers. To overcome selection bias, we performed 1:1 propensity score matching. Our primary outcome was overall survival. RESULTS: After propensity score matching, each group comprised 96 patients, with no significant differences in any baseline characteristics. The median survival was significantly longer in the metal stenting group than in the plastic stenting group (7.2 months [95% CI 6.0-8.5] vs. 4.1 months [95% CI 2.9-5.3]; P = 0.015). The clinical success rates were significantly higher in the metal stenting group than in the plastic stenting group (99.0% vs. 71.9%, respectively; P < 0.001), and lower post-procedure cholangitis incidence (7.3% vs. 26.0%; P < 0.001), longer median symptom-free stent patency (9.2 months [95% CI 7.6-10.6] vs. 4.8 months [95% CI 4.2-5.3]; P < 0.001), and fewer total interventions (1.3 ± 0.6 vs. 2.0 ± 1.4; P < 0.001). In multivariate Cox analysis of the overall survival, metal stenting (HR 0.589, P = 0.002), hilar cholangiocarcinoma (HR 0.419, P = 0.009), and adjuvant treatment (HR 0.596, P = 0.006) were independent predictors of death. CONCLUSIONS: Endoscopic therapy using bilateral metal stenting is superior to bilateral plastic stenting, with prolonged overall survival, higher clinical success, and longer stent patency in patients with advanced hilar biliary malignancies.

Facile Fabrication of Oxidation-Responsive Polymeric Nanoparticles for Effective Anticancer Drug Delivery.

Reactive oxygen species (ROS) are highly overproduced in cancerous tissues, and thus oxidation-responsive nanoparticles (NPs) have emerged as a promising drug carrier for cancer-targeted drug delivery. In this study, we successfully synthesized poly(vanillyl alcohol- co-oxalate) (PVAX) polymer with an excellent ROS-responsive capacity. A well-established emulsion-solvent evaporation method was used to fabricate PVAX-based curcumin (CUR)-loaded NPs (PVAX-NPs) and their counterparts (poly(lactic- co-glycolic acid)-based CUR-loaded NPs, PLGA-NPs). It was found that these NPs had a hydrodynamic particle size of approximately 245 nm, narrow size distribution (polydispersity index less than 0.1), negative zeta potential (around -18 mV), smooth surface appearance, and high drug encapsulation efficiency. Moreover, we found that the CUR release rate of PVAX-NPs was greatly increased in the presence of a hydrogen peroxide-rich environment due to the cleavage of polyoxalate ester bonds in PVAX polymer, resulting in the evenly distribution of CUR within the whole cancer cells. More importantly, PVAX-NPs exhibited much stronger anticancer activities and pro-apoptotic capacities than PLGA-NPs both in vitro and in vivo. These results clearly demonstrate that these ROS-responsive PVAX-NPs can be exploited as a robust anticancer drug delivery platform in chemotherapy.

Evaluation of fixed-jaw IMRT and tangential partial-VMAT radiotherapy plans for synchronous bilateral breast cancer irradiation based on a dosimetric study.

PURPOSE: To investigate the fixed-jaw intensity-modulated radiotherapy (F-IMRT) and tangential partial volumetric modulated arc therapy (tP-VMAT) treatment plans for synchronous bilateral breast cancer (SBBC). MATERIALS AND METHOD: Twelve SBBC patients with pTis-2N0M0 stages who underwent whole-breast irradiation after breast-conserving surgery were planned with F-IMRT and tP-VMAT techniques prescribing 42.56 Gy (2.66 Gy*16f) to the breast. The F-IMRT used 8-12 jaw-fixed tangential fields with single (sF-IMRT) or two (F-IMRT) isocenters located under the sternum or in the center of the left and right planning target volumes (PTVs), and tP-VMAT used 4 tangential partial arcs with two isocenters located in the center of the left and right PTVs. Plan evaluation was based on dose-volume histogram (DVH) analysis. Dosimetric parameters were calculated to evaluate plan quality; total monitor units (MUs), and the gamma analysis for patient-specific quality assurance (QA) were also evaluated. RESULTS: For PTVs, the three plans had similar Dmean and conformity index (CI) values. F-IMRT showed a slightly better target coverage according to the V100% values and demonstrated an obvious reduction in V105% and Dmax compared with the values observed for sF-IMRT and tP-VMAT. Compared with tP-VMAT, sF-IMRT was slightly better in terms of V100% , V105% and Dmax . In addition, F-IMRT achieved the best homogeneity index (HI) values for PTVs. Concerning healthy tissue, tP-VMAT had an advantage in minimizing the high dose volume. The MUs of the tP-VMAT plan were decreased approximately 1.45 and 1 times compared with the sF-IMRT and F-IMRT plans, respectively, and all plans passed QA. For the lungs, heart and liver, F-IMRT achieved the smallest values in terms of Dmean and showed a significant difference compared with tP-VMAT. Simultaneously, sF-IMRT was also superior to tP-VMAT. For the coronary artery, tP-VMAT achieved the lowest Dmean , while the value for F-IMRT was 2.24% lower compared with sF-IMRT. For all organs at risk (OARs), tP-VMAT was superior at the high dose level. In contrast, sF-IMRT and F-IMRT were obviously superior at the low dose level. The sF-IMRT and F-IMRT plans showed consistent trends. CONCLUSION: All treatment plans for the provided techniques were of high quality and feasible for SBBC patients. However, we recommend F-IMRT with a single isocenter as a priority technique because of the tremendous advantage of local hot spot control in PTVs and the reduced dose to OARs at low dose levels. When the irradiated dose to the lungs and heart exceed the clinical restriction, two isocenter F-IMRT can be used to maximize OAR sparing. Additionally, tP-VMAT can be adopted for improving cold spots in PTVs or high-dose exposure to normal tissue when the interval between PTVs is narrow.

Design and Synthesis of a Novel n-Type Polymer Based on Asymmetric Rylene Diimide for the Application in All-Polymer Solar Cells.

A novel n-type polymer of PTDI-T based on asymmetric rylene diimide and thiophene is designed and synthesized. The highest power conversion efficiency of 4.70% is achieved for PTB7-Th:PTDI-T-based devices, which is obviously higher than those of the analogue polymers of PPDI-2T and PDTCDI. When using PBDB-T as a donor, an open-circuit voltage (VOC ) as high as 1.03 V is obtained. The results indicate asymmetric rylene diimide is a kind of promising building block to construct n-type photovoltaic polymers.

Acid-Activatable Theranostic Unimolecular Micelles Composed of Amphiphilic Star-like Polymeric Prodrug with High Drug Loading for Enhanced Cancer Therapy.

Stimuli-responsive nanomedicine with theranostic functionalities with reduced side-effects has attracted growing attention, although there are some major obstacles to overcome before clinical applications. Herein, we present an acid-activatable theranostic unimolecular micelles based on amphiphilic star-like polymeric prodrug to systematically address typical existing issues. This smart polymeric prodrug has a preferable size of about 35 nm and strong micellar stability in aqueous solution, which is beneficial to long-term blood circulation and efficient extravasation from tumoral vessels. Remarkably, the polymeric prodrug has a high drug loading rate up to 53.1 wt%, which induces considerably higher cytotoxicity against tumor cells (HeLa cells and MCF-7 cells) than normal cells (HUVEC cells) suggesting a spontaneous tumor-specific targeting capability. Moreover, the polymeric prodrug can serve as a fluorescent nanoprobe activated by the acidic microenvironment in tumor cells, which can be used as a promising platform for tumor diagnosis. The superior antitumor effect in this in vitro study demonstrates the potential of this prodrug as a promising platform for drug delivery and cancer therapy.

[Safety evaluation and risk control measures of Cassiae Semen].

In this study, the authors reviewed domestic and foreign literatures, conducted the textual research on origin and development of Cassia Semen, studied records in ancient books and ancient and modern literatures, clinical adverse reactions and relevant experimental studies in recent years, and summarized the clinical features and influencing factors related to the safety of Cassiae Semen. According to the findings,Cassia Semen's safety risks are mainly liver and kidney system damages, with the main clinical features of fatigue, anorexia, disgusting of oil, yellow urine and gray stool; digestive system injury, with the main clinical features of diarrhea, abdominal distension, nausea and loose stool; reproductive system damage, with the main clinical features of vaginal bleeding. Allergic reactions and clinical adverse events, with the main clinical features for numb mouth, itching skin, nausea and vomiting, diarrhea, wheezing and lip cyanosis were also reported. The toxicological studies on toxic components of Cassiae Semen obtusifolia were carried out through acute toxicity test, subacute toxicity test, subchronic toxicity test and chronic toxicity test. Risk factors might include patients, compatibility and physicians. Physicians should strictly abide by the medication requirements in the Pharmacopoeia, pay attention to rational compatibility, appropriate dosage,correct usage and appropriate processing, control the dosage below 15 g to avoid excessive intake, strictly control the course of treatment to avoid accumulated poisoning caused by long-term administration. At the same time, clinicians should pay attention to the latest research progress, update the knowledge structure, quickly find the latest and useful materials from clinical practice, scientific research and drug information and other literatures, make evaluation and judgment for the materials, establish a traditional Chinese medicine intelligence information library, and strengthen the control over adverse effects with a pre-warning consciousness. The authors suggested standardizing clinical medication of Cassiae Semen, and avoiding misuse or excessive use; clinicians should prescribe it in strict accordance with there commended usage and dosage in the Pharmacopoeia, and focus on the safety signal accumulation in clinic, while strengthening studies for toxic substance basis and toxicity mechanism, in order to give full play to Cassiae Semen's clinical efficacy and reduce its adverse reactions.

Detection of TDP-43 oligomers in frontotemporal lobar degeneration-TDP.

OBJECTIVE: The proteinaceous inclusions in TDP-43 proteinopathies such as frontotemporal lobar degeneration (FTLD)-TDP are made of high-molecular-weight aggregates of TDP-43. These aggregates have not been classified as amyloids, as prior amyloid staining results were not conclusive. Here we used a specific TDP-43 amyloid oligomer antibody called TDP-O to determine the presence and abundance of TDP-43 oligomers among different subtypes of FTLD-TDP as well as in hippocampal sclerosis (HS), which represents a non-FTLD pathology with TDP-43 inclusions. METHODS: Postmortem tissue from the hippocampus and anterior orbital gyrus from 54 prospectively assessed and diagnosed subjects was used for immunostaining with TDP-O. Electron microscopy was used to assess the subcellular locations of TDP-O-decorated structures. RESULTS: TDP-43 inclusions staining with TDP-O were present in FTLD-TDP and were most conspicuous for FTLD-TDP type C, the subtype seen in most patients with semantic variant primary progressive aphasia. TDP-O immunoreactivity was absent in the hippocampus of HS patients despite abundant TDP-43 inclusions. Ultrastructurally, TDP-43 oligomers resided in granular or tubular structures, frequently in close proximity to, but not within, neuronal lysosomes. INTERPRETATION: TDP-43 forms amyloid oligomers in the human brain, which may cause neurotoxicity in a manner similar to other amyloid oligomers. Oligomer formation may contribute to the conformational heterogeneity of TDP-43 aggregates and mark the different properties of TDP-43 inclusions between FTLD-TDP and HS.

[Comparison of effectiveness and safety between Twisted File technique and ProTaper Universal rotary full sequence based on micro-computed tomography].

OBJECTIVE: To evaluate the efficacy and security of two type of rotary nickel titanium system (Twisted File and ProTaper Universal) for root canal preparation based on micro-computed tomography(micro-CT). METHODS: Twenty extracted molars (including 62 canals) were divided into two experimental groups and were respectively instrumented using Twisted File rotary nickel titanium system (TF) and ProTaper Universal rotary nickel titanium system (PU) to #25/0.08 following recommended protocol. Time for root canal instrumentation (accumulation of time for every single file) was recorded. The 0-3 mm root surface from apex was observed under an optical stereomicroscope at 25 × magnification. The presence of crack line was noted. The root canals were scanned with micro-CT before and after root canal preparation. Three-dimensional shape images of canals were reconstructed, calculated and evaluated. The amount of canal central transportation of the two groups was calculated and compared. RESULTS: The shorter preparation time [(0.53 ± 0.14) min] was observed in TF group, while the preparation time of PU group was (2.06 ± 0.39) min (P<0.05). In mid-root level, TF group shaping resulted in less canal center transportation than PU group [(0.070 ± 0.056) mm vs. (0.097 ± 0.084) mm, P<0.05]. No instrument separation was observed in both the groups. Cracks were not found in both the groups either based in micro-CT images or observation under an optical stereomicroscope at 25 × magnification. CONCLUSION: Compared with ProTaper Universal, Twisted File took less time in root canal preparation and exhibited better shaping ability, and less canal transportation.

Safety and efficacy of a novel plastic stent coated with stone-dissolving agents for the treatment of biliary stones in a porcine model.

BACKGROUND AND STUDY AIM: We previously reported on a plastic stent that was coated with ethylenediaminetetraacetic acid (EDTA) and sodium cholate, which dissolved common bile duct (CBD) stones ex vivo. The aim of this study was to investigate the safety and efficacy of such stents on biliary stones in a live porcine model. METHODS: Stents without coating or with degradable membranes containing 0 % or 50 % EDTA and sodium cholate were inserted together with human CBD stones into the porcine CBD. Serum laboratory variables, histological examinations of the bile duct, and the weight change in stones were compared during and after stent placement for 6 months. RESULTS: A total of 16 pigs were included (5 no coating, 5 0 % coating, 6 50 % coating). Biliary stones showed decreased weight in all groups; however, stones in the group with 50 % coated stents showed a greater reduction in weight compared with the no coating and the 0 % coating groups (269 ±â€Š66 mg vs. 179 ±â€Š51 mg [P = 0.09]; 269 ±â€Š66 mg vs. 156 ±â€Š26 mg [P = 0.01], respectively). CONCLUSIONS: The plastic stent coated with 50 % agent enhanced CBD stone dissolution in vivo and may be a promising tool for patients with difficult biliary stones.

Targeting intestinal inflammation with CD98 siRNA/PEI-loaded nanoparticles.

Intestinal CD98 expression plays a crucial role in controlling homeostatic and innate immune responses in the gut. Modulation of CD98 expression in intestinal cells therefore represents a promising therapeutic strategy for the treatment and prevention of inflammatory intestinal diseases, such as inflammatory bowel disease. Here, the advantages of nanoparticles (NPs) are used, including their ability to easily pass through physiological barriers and evade phagocytosis, high loading concentration, rapid kinetics of mixing and resistance to degradation. Using physical chemistry characterizations techniques, CD98 siRNA/polyethyleneimine (PEI)-loaded NPs was characterized (diameter of ~480 nm and a zeta potential of -5.26 mV). Interestingly, CD98 siRNA can be electrostatically complexed by PEI and thus protected from RNase. In addition, CD98 siRNA/PEI-loaded NPs are nontoxic and biocompatible with intestinal cells. Oral administration of CD98/PEI-loaded NPs encapsulated in a hydrogel reduced CD98 expression in mouse colonic tissues and decreased dextran sodium sulfate-induced colitis in a mouse model. Finally, flow cytometry showed that CD98 was effectively downregulated in the intestinal epithelial cells and intestinal macrophages of treated mice. Finally, the results collectively demonstrated the therapeutic effect of "hierarchical nano-micro particles" with colon-homing capabilities and the ability to directly release "molecularly specific" CD98 siRNA in colonic cells, thereby decreasing colitis.

ClpP affects biofilm formation of Streptococcus mutans differently in the presence of cariogenic carbohydrates through regulating gtfBC and ftf.

The abilities to form biofilms on teeth surface and to metabolize a wide range of carbohydrates are key virulence attributes of Streptococcus mutans. ClpP has been proved to play an important role in biofilm development in streptococci. Here we demonstrated that ClpP was involved in biofilm formation of S. mutans. ClpP inactivation resulted in enhanced biofilm formation or initial cell adherence in broth supplemented with sucrose, while reduced in broth supplemented with glucose or fructose. Our results also indicated that the enhanced capacities of biofilm formation and initial cell adherence were achieved through regulating the expression of a number of extracellular sucrose-metabolizing enzymes, such as glucosyltransferases (GTFB and GTFC) at early-exponential growth phase and fructosyltransferase at late-exponential growth phase in the presence of sucrose.

Electrochemical DNA hybridization sensors based on conducting polymers.

Conducting polymers (CPs) are a group of polymeric materials that have attracted considerable attention because of their unique electronic, chemical, and biochemical properties. This is reflected in their use in a wide range of potential applications, including light-emitting diodes, anti-static coating, electrochromic materials, solar cells, chemical sensors, biosensors, and drug-release systems. Electrochemical DNA sensors based on CPs can be used in numerous areas related to human health. This review summarizes the recent progress made in the development and use of CP-based electrochemical DNA hybridization sensors. We discuss the distinct properties of CPs with respect to their use in the immobilization of probe DNA on electrode surfaces, and we describe the immobilization techniques used for developing DNA hybridization sensors together with the various transduction methods employed. In the concluding part of this review, we present some of the challenges faced in the use of CP-based DNA hybridization sensors, as well as a future perspective.

Vertebroplasty versus kyphoplasty in osteoporotic vertebral compression fracture: a meta-analysis of prospective comparative studies.

PURPOSE: The goal of this article is to evaluate the efficacy and the safety of the percutaneous vertebroplasty (PVP) versus percutaneous kyphoplasty (PKP) in dealing with the osteoporotic vertebral compression fracture (OVCF). METHODS: In July 2014, a comprehensive systematic computer-based online search was performed by using the databases of PubMed, EMBASE, Cochrane Library, Web of Science, Wan Fang, and the China Biological Medicine. Only prospective comparative trials (PCT) and randomized controlled trials (RCT) that compared PVP with PKP were included. Trials were screened based on the inclusion and exclusion criteria previously formed. The Cochrane collaboration guidelines were also used to assess the quality of these included studies. The primary data of these studies [volume of the cement, postoperative vertebral height, visual analog scale (VAS) score and Oswestry Disability Index (ODI) score after the surgery, and so on] were carefully abstracted and processed by Revman 5.2.0 software The publication bias of the main results (cement leakage and adjacent-level fracture) were examined by Stata 12.0 (Begg and Egger test). Furthermore, the stability of the main results were also detected by sensitivity and cumulative analyses. RESULTS: Six RCT and 14 PCT studies involving 1,429 patients met our criteria and were included finally. Comparing these two methods, the PKP group took more operation time [SMD = 0.66, 95 % CI (0.28, 1.03), p = 0.0006] with higher anterior vertebral body height [SMD = 1.40, 95 % CI (0.49, 2.32), p = 0.003], greatly reduced Cobb angle in the long run [SMD = -0.61, 95 % CI (-1.04, -0.19), p = 0.005] and had lower risk of cement leakage. However, in VAS scores and ODI scores after the surgery whether for the short-term efficacy (no more than 1 week after the surgery) or long-term efficacy (more than six months), Cobb angle in the short run and new fracture in the adjacent level, no statistically differences were found between the two groups. CONCLUSIONS: Based on current evidence, PVP takes less time in the operation, while it has greater risk of cement leakage, was inferior in reducing Cobb angle in the long term and results in lower anterior vertebral body height after the surgery. For pain relief, which is the main desire of the patients, both procedures provide significant improvement in VAS and ODI pain scores. PVP is still an effective procedure.

The effect of a novel drug-eluting plastic stent on biliary stone dissolution in an ex vivo bile perfusion model.

BACKGROUND: Temporary plastic stent insertion has been considered a safe and effective bridge therapy for difficult common bile duct (CBD) stones. Infusing chemicals to directly dissolve stones through the bile duct might also be effective. However, there are no studies on the efficacy of the combination of these 2 approaches. OBJECTIVE: To investigate the efficacy of a novel ethylenediaminetetraacetic acid (EDTA) and sodium cholate-eluting plastic stent on biliary stones. DESIGN: Ex vivo model by using different doses of active ingredient. SETTING AND INTERVENTIONS: An ex vivo bile duct model perfused with porcine bile was created. Stents coated with degradable membranes containing various concentrations of EDTA and sodium cholate were placed in the model with CBD stones. MAIN OUTCOME MEASUREMENTS: The change in the weight of stents and stones was measured every week during perfusion until the coated membranes were completely biodegraded. RESULTS: The time that the stents required to be fully degraded and the efficiency of stone dissolution were positively correlated with the percentage of EDTA and sodium cholate in the stent membrane. However, the 50% EDTA and sodium cholate stents achieved the greatest percentage of stone weight loss when the drugs were completely released. LIMITATIONS: Ex vivo study. CONCLUSIONS: The EDTA and sodium cholate-eluting plastic stent effectively dissolved CBD stones and has prospect in the therapy for patients with difficult CBD stones.

Contribution of ClpP to stress tolerance and virulence properties of Streptococcus mutans.

Abilities to tolerate environmental stresses and to form biofilms on teeth surface are key virulence attributes of Streptococcus mutans, the primary causative agent of human dental caries. ClpP, the chief intracellular protease of S. mutans, along with ATPases degrades altered proteins that might be toxic for bacteria, and thus plays important roles in stress response. To further understand the roles of ClpP in stress response of S. mutans, a ClpP deficient strain was constructed and used for general stress tolerance, autolysis, mutacins production, and virulence assays. Here, we demonstrated that inactivation of ClpP in S. mutans resulted in a sensitive phenotype to several environmental stresses, including acid, cold, thermal, and oxidative stresses. The ClpP deficient strain displayed slow growth rates, poor growth yields, formation of long chains, increased clumping in broth, and reduced capacity to form biofilms in presence of glucose. Mutacins production and autolysis of S. mutans were also impaired by mutation of clpP. Animals study showed that clpP mutation increased virulence of S. mutans but not significant. However, enhanced abilities to survive lethal acid and to form biofilm in sucrose were observed in ClpP deficient strain. Our findings revealed a broad impact of ClpP on several virulence properties of S. mutans and highlighted the relevance of ClpP proteolysis with progression of diseases caused by S. mutans.