Non-Clinical Safety Evaluation of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys.

Purpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future. Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection. Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group. Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.

Transcriptome-Wide Analysis of Core Transcription Factors Associated with Defense Responses in Autotetraploid versus Diploid Rice under Saline Stress and Recovery.

Saline stress is a major abiotic stress that inhibits plant growth and yields worldwide. The plant transcription factor (TF) family plays an important role in converting abiotic stress signals into gene expression changes. In this study, a transcriptome-based comparative analysis was performed to investigate the global gene expression of all the TFs in diploid and autotetraploid rice during the early stage of NaCl stress and recovery period. The phenotypic data indicated that the tetraploid rice exhibited a superior salt-tolerant ability compared to the diploid rice. A total of 55 TF families were co-expressed in the tetraploid and diploid rice, and the cumulative number of TF-expressed genes was relatively higher in the diploid rice than in the tetraploid rice at all time points. Unlike the diploid rice, the overall gene expression levels of the tetraploid rice were comparable to the control during recovery. The number of differentially expressed TFs (DE-TFs) in the tetraploid rice decreased after recovery, whereas it increased to a large extent in the diploid rice. GO and KEGG pathway enrichment analysis of the DE-TFs discovered the early switching of the ABA-activated signaling pathway and specific circadian rhythm in the tetraploid rice. Combining the PPI network and heatmap analysis, some core DE-TFs were found that may have potential roles to play in tetraploid salt tolerance. This study will pave the way for elucidating the complex network regulatory mechanisms of salt tolerance in tetraploid rice.

Chimeric CNS-targeting-peptide engineered exosomes for experimental autoimmune encephalomyelitis therapy.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that causes demyelination, neuronal damage and white matter loss, but there is still no known cure. Exosomes are 30-200 nm-sized double-layered membrane vesicles that can easily cross the blood-brain barrier (BBB). Exosomes from umbilical cord mesenchymal stem cells（UMSCs） have been found to treat experimental autoimmune encephalomyelitis (EAE) through the action of anti-inflammatory and immunomodulatory, but its clinical translation has been hampered by their inefficacious accumulation in CNS. Therefore, we developed a TAxI-exos, also known as a TAxI-peptide-chimeric UMSC-exos, for CNS-specific accumulation and curative effect in EAE. We used the EAE model in vivo as well as active T cell and BV-2 cell models in vitro to explore the efficacy and mechanisms. Exosomes from UMSCs with TAxI or DiR labels were given to EAE mice in one dosage (150 g) prior to the peak at day 15. The mice were sacrificed on day 30 so that spinal cords, spleens, and blood could be taken for analysis of demyelination, inflammation, microglia, T-cell subset proportions, and inflammatory cytokine expression. In vitro, PBMCs and splenocytes isolated from healthy C57BL/6 mice were activated and incubated with 0.15 mg/mL of UMSC-exos or TAxI-exos for immune mechanism investigations. Activated BV-2 cells were used to investigate the targeting and controlling polarization ability and mechanism of UMSC-exos and TAxI-exos. As expected, TAxI-exos exhibited significantly greater therapeutic action in EAE mice than UMSC-exos due to their improved targeting-ability. The medication reduced T-cell subset proportions and inflammation, reduced active-microglia proportions and promoted M1 to M2 microglial cell polarization through TNF pathway, upregulated IL-4, IL-10, TGF-ß, and IDO-1 expression, and downregulated IL-2, IL-6, IL-17A, IFN-γ, and TNF-α. The CNS-targeting properties of TAxI-exos and their capacity to inhibit degenerative processes in EAE mice have considerable potential therapeutic value for MS and other CNS illnesses.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Evaluating the Differential Response of Transcription Factors in Diploid versus Autotetraploid Rice Leaves Subjected to Diverse Saline-Alkali Stresses.

Saline-alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline-alkali stress than its donor counterparts, which is reflected by differential gene expression between autotetraploid and diploid rice in response to salt, alkali, and saline-alkali stress. In this study, we investigated the expression of the transcription factors (TFs) in the leaf tissues of autotetraploid and diploid rice under different types of saline-alkali stress. Transcriptome analysis identified a total of 1040 genes from 55 TF families that were altered in response to these stresses, with a significantly higher number in autotetraploid rice compared to diploid rice. Contrarily, under these stresses, the number of expressed TF genes in autotetraploid rice was greater than that in diploid rice for all three types of stress. In addition to the different numbers, the differentially expressed TF genes were found to be from significantly distinct TF families between autotetraploid and diploid rice genotypes. The GO enrichment analysis unraveled that all the DEGs were distributed with differentially biological functions in rice, in particular those that were enriched in the pathways of phytohormones and salt resistance, signal transduction, and physiological and biochemical metabolism in autotetraploid rice compared to its diploid counterpart. This may provide useful guidance for studying the biological roles of polyploidization in plant resilience in response to saline-alkali stress.

Functionalized Cortical Bone-Inspired Composites Adapt to the Mechanical and Biological Properties of the Edentulous Area to Resist Fretting Wear.

Dental implants with long-term success of osseointegration have always been the goal, however, difficulties exist. The accumulation of fretting damage at the implant-bone interface often gets overlooked. Commonly used titanium is approximately 7-fold harder and stiffer than cortical bone. Stress shielding caused by the mismatching of the elastic modulus aggravates fretting at the interface, which is accompanied by the risk of the formation of proinflammatory metal debris and implant loosening. Thus, the authors explore functionalized cortical bone-inspired composites (FCBIC) with a hierarchical structure at multiple scales, that exhibit good mechanical and biological adaptivity with cortical bone. The design is inspired by nature, combining brittle minerals with organic molecules to maintain machinability, which helps to acquire excellent energy-dissipating capability. It therefore has the comparable hardness and elastic modulus, strength, and elastic-plastic deformation to cortical bone. Meanwhile, this cortical bone analogy exhibits excellent osteoinduction and osseointegration abilities. These two properties also facilitate each other to resist fretting wear, and therefore improve the success rate of implantation. Based on these results, the biological-mechanical co-operation coefficient is proposed to describe the coupling between these two factors for designing the optimized dental implants.

Accuracy of Intraoperative Measuring Guide and Conventional Surgical Guide in Anterior Implant Surgery: A Retrospective Case-Control Study

PURPOSE: To verify a novel method that improves the accuracy of static computer-aided implant surgery (sCAIS) through intraoperative measurement. MATERIALS AND METHODS: Forty-seven patients were selected for this study, each with a missing tooth or a tooth that required extraction from the anterior area. The patients were divided into the intraoperative measuring guide (MG) and conventional guide (CG) groups. Following the preoperative implant planning, the surgical guides were designed and fabricated. In the MG group, the drill was guided by double-armed zirconia sleeves, and the axial direction of the drill was assessed using the indicator components. The implant was guided using a resin guide tube. In the CG group, the drills were guided using a metal sleeve and handles, and the implants were placed with the guidance of the metal sleeve only. The angular and linear deviations at the entry and apex between the planned and actual implant positions were measured after matching the preoperative and postoperative CBCT data. The independent-samples t test was used to compare the deviation between the MG and CG groups. RESULTS: The 3D deviations for the MG group at the entry and apex were 0.67 ± 0.44 mm and 0.93 ± 0.40 mm, respectively. The angular deviation was 2.27 ± 0.96 degrees. Statistical differences were found in the 3D deviation at the entry point and apical position between the MG and CG groups, yielding relatively smaller deviations in the MG group. CONCLUSION: The use of an intraoperative measuring guide could improve the accuracy of implant placement in sCAIS.

Comparative Analysis of Physiological, Hormonal and Transcriptomic Responses Reveal Mechanisms of Saline-Alkali Tolerance in Autotetraploid Rice (Oryza sativa L.).

Saline-alkali soil has posed challenges to the growth of agricultural crops, while polyploidy often show greater adaptability in diverse and extreme environments including saline-alkali stress, but its defense mechanisms in rice remain elusive. Herein, we explored the mechanisms of enhanced saline-alkali tolerance of autotetraploid rice 93-11T relative to diploid rice 93-11D, based on physiological, hormonal and transcriptomic profilings. Physiologically, the enhanced saline-alkali tolerance in 93-11T was manifested in higher soluble sugar accumulation and stronger superoxide dismutase (SOD) and peroxidase (POD) activities in leaves during 24 h after saline-alkali shock. Furthermore, various hormone levels in leaves of 93-11T altered greatly, such as the negative correlation between salicylic acid (SA) and the other four hormones changed to positive correlation due to polyploidy. Global transcriptome profiling revealed that the upregulated differentially expressed genes (DEGs) in leaves and roots of 93-11T were more abundant than that in 93-11D, and there were more DEGs in roots than in leaves under saline-alkali stress. Genes related to phytohormone signal transduction of auxin (AUX) and SA in roots, lignin biosynthesis in leaves or roots, and wax biosynthesis in leaves were obviously upregulated in 93-11T compared with 93-11D under saline-alkali condition. Collectively, 93-11T subjected to saline-alkali stress possibly possesses higher osmotic regulation ability due to cuticular wax synthesis, stronger negative regulation of reactive oxygen species (ROS) production by increasing the SA levels and maintaining relative lower levels of IAA, and higher antioxidant capacity by increasing activities of SOD and POD, as well as lignin biosynthesis. Our research provides new insights for exploring the mechanisms of saline-alkali tolerance in polyploid rice and discovering new gene targets for rice genetic improvement.

Autotetraploidization Gives Rise to Differential Gene Expression in Response to Saline Stress in Rice.

Plant polyploidization represents an effective means for plants to perpetuate their adaptive advantage in the face of environmental variation. Numerous studies have identified differential responsiveness to environmental cues between polyploids and their related diploids, and polyploids might better adapt to changing environments. However, the mechanism that underlies polyploidization contribution during abiotic stress remains hitherto obscure and needs more comprehensive assessment. In this study, we profile morphological and physiological characteristics, and genome-wide gene expression between an autotetraploid rice and its diploid donor plant following saline stress. The results show that the autotetraploid rice is more tolerant to saline stress than its diploid precursor. The physiological characteristics were rapidly responsive to saline stress in the first 24 h, during which the elevations in sodium ion, superoxide dismutase, peroxidase, and 1-aminocyclopropane-1-carboxylic acid were all significantly higher in the autotetraploid than in the diploid rice. Meanwhile, the genome-wide gene expression analysis revealed that the genes related to ionic transport, peroxidase activity, and phytohormone metabolism were differentially expressed in a significant manner between the autotetraploid and the diploid rice in response to saline stress. These findings support the hypothesis that diverse mechanisms exist between the autotetraploid rice and its diploid donor plant in response to saline stress, providing vital information for improving our understanding on the enhanced performance of polyploid plants in response to salt stress.

Application of measurable surgical guides in immediate implant placement and immediate restoration.

This article reports a case of using immediate implant placement and immediate restoration combined with measurable implant surgical guides to restore compromised maxillary incisors caused by dental trauma. Target restoration was designed in the exoCAD software preoperatively, intraoral measurements were obtained in three directions, and the correct position of virtual implants was determined in BlueSky Plan 4. Afterward, measurable implant guides were designed and fabricated by 3D printing. Under the guidance of the measurable implant surgical guides and intraoperative measurement, the entry point was determined, the axial direction was verified when drilling to half the depth, and the 3D position was verified when drilling to total depth. Implants were inserted followed by verification once again. The temporary restoration, which was designed based on the target restoration and emergence profile of the original teeth and milled preoperatively, was connected to the implant immediately after surgery. Postoperative accuracy analysis showed that the mean linear deviations between the actual implant position and the pre-planned position were (0.57±0.17) mm at the entry point and (0.82±0.27) mm at the apex, and the mean angular deviation was (1.86±0.89) °, demonstrating that precise implant placement and immediate restoration were implemented.

Circ_0008768 Suppresses the Pancreatic Cancer Progression via miR-330- 3p/PTEN Axis.

OBJECTIVE: To probe the role of circular RNA_0008768 (circ_0008768) in the development of pancreatic cancer (PC) and its regulatory mechanism. METHODS: The expression levels of circ_0008768, miR-330-3p, and PTEN mRNA in PC tissues and cells were detected using qRT-PCR. Cell proliferation, migration and invasion of PC cells were detected by CCK-8 method, EdU method, and Transwell assay. The targeting relationship between circ_0008768 and miR-330-3p, as well as miR-330-3p and PTEN mRNA 3'UTR was analyzed by the dual-luciferase reporter assay. PTEN expression levels in PC cells were analyzed by Western blot. RESULTS: The expression levels of circ_0008768 and PTEN mRNA were significantly reduced in both PC tissues and cell lines. Overexpression of circ_0008768 exerted an inhibitory effect on the proliferation, migration and invasion of PC cells. Knocking down circ_0008768 showed the opposite effect. Circ_0008768 directly targeted and negatively regulated the expression of miR-330- 3p. PTEN was identified as a downstream target gene of miR-330-3p. Circ_0008768 could positively regulate the expression of PTEN. CONCLUSION: In PC, circ_0008768 can act as a tumor-suppressive factor to inhibit the development of PC by regulating the miR-330-3p/PTEN molecular axis.

Alkaline Stress Induces Different Physiological, Hormonal and Gene Expression Responses in Diploid and Autotetraploid Rice.

Saline-alkaline stress is a critical abiotic stress that negatively affects plants' growth and development. Considerably higher enhancements in plant tolerance to saline-alkaline stress have often been observed in polyploid plants compared to their diploid relatives, the underlying mechanism of which remains elusive. In this study, we explored the variations in morphological and physiological characteristics, phytohormones, and genome-wide gene expression between an autotetraploid rice and its diploid relative in response to alkaline stress. It was observed that the polyploidization in the autotetraploid rice imparted a higher level of alkaline tolerance than in its diploid relative. An eclectic array of physiological parameters commonly used for abiotic stress, such as proline, soluble sugars, and malondialdehyde, together with the activities of some selected antioxidant enzymes, was analyzed at five time points in the first 24 h following the alkaline stress treatment between the diploid and autotetraploid rice. Phytohormones, such as abscisic acid and indole-3-acetic acid were also comparatively evaluated between the two types of rice with different ploidy levels under alkaline stress. Transcriptomic analysis revealed that gene expression patterns were altered in accordance with the variations in the cellular levels of phytohormones between diploid and autotetraploid plants upon alkaline stress. In particular, the expression of genes related to peroxide and transcription factors was substantially upregulated in autotetraploid plants compared to diploid plants in response to the alkaline stress treatment. In essence, diploid and autotetraploid rice plants exhibited differential gene expression patterns in response to the alkaline stress, which may shed more light on the mechanism underpinning the ameliorated plant tolerance to alkaline stress following genome duplication.

N6-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner.

Emerging evidence has emphasized the critical roles played by N6-methyladenosine RNA (m6A) modification in colorectal carcinoma (CRC) initiation and progression. However, the roles and mechanism of m6A and KIAA1429 in CRC progression require further clarification. Here, our research aimed to investigate the functions of KIAA1429 in CRC tumorigenesis. Results indicated that KIAA1429 up-regulation closely correlated to the poor prognosis of CRC patients. Bio-functional assays demonstrated that KIAA1429 promoted the aerobic glycolysis, including glucose uptake, lactate production, ATP generation and extracellular acidification rate (ECAR). Mechanistically, KIAA1429 positively up-regulated HK2 level via increasing its mRNA stability by binding the m6A site of HK2 mRNA via m6A-independent manner. Collectively, our work indicates that KIAA1429 has the potential to promote CRC carcinogenesis by targeting HK2 via m6A-independent manner, providing insight into the critical roles of m6A in CRC.

Identification and characterization of TYK2 pseudokinase domain stabilizers that allosterically inhibit TYK2 signaling.

Kinase inhibition continues to be a major focus of pharmaceutical research and discovery due to the central role of these proteins in the regulation of cellular processes. One family of kinases of pharmacological interest, due to its role in activation of immunostimulatory pathways, is the Janus kinase family. Small molecule inhibitors targeting the individual kinase proteins within this family have long been sought-after therapies. High sequence and structural similarity of the family members makes selective inhibitors difficult to identify but critical because of their inter-related multiple cellular regulatory pathways. Herein, we describe the identification of inhibitors of the important Janus kinase, TYK2, a regulator of type I interferon response. In addition, the biochemical and structural confirmation of the direct interaction of these small molecules with the TYK2 pseudokinase domain is described and a potential mechanism of allosteric regulation of TYK2 activity through stabilization of the pseudokinase domain is proposed.

Improvement in Osseointegration of Titanium Dental Implants After Exposure to Ultraviolet-C Light for Varied Durations: An Experimental Study in Beagle Dogs.

PURPOSE: Ultraviolet-mediated photofunctionalization is a valid technology for enhancing the osseointegration of titanium implants. However, there is no consensus on the effective exposure time to ultraviolet light. The objective of this study was to evaluate the effect of different exposure times of ultraviolet-C (UVC) light on aged titanium implants and explore the optimal treatment duration of UVC photofunctionalization for osseointegration in an animal model. METHODS: Eight male beagle dogs (n = 48) were divided into a control group (n = 12) and 3 experimental groups (n = 12/12/12) which received 4-week-old implants without UVC treatment (C) or treated with UVC for 1/6 hour, 1/2 hour, and 1 hour (UVC-1/6 hour, UVC-1/2 hour, UVC-1 hour) immediately before placement. All the implants were placed 12 weeks after mandibular premolars extraction. Four dogs were euthanized after 4 and 12 weeks of healing, respectively. The marginal bone level and implant stability quotient were measured at implant placement and after sacrifice. Subsequently, micro-CT and histomorphometric analyses were performed following block harvesting. RESULTS: No significant difference in marginal bone loss between the UVC-untreated and UVC-treated groups was found at 4 or 12 weeks. At 4 weeks, significantly higher BV/TV and bone-implant contact were observed in the UVC groups than in the C group, irrespective of the UVC-photofunctionalization duration (BV/TV: UVC-1/6 hour 0.48 ± 0.11, UVC-1/2 hour 0.50 ± 0.06, and UVC-1 hour 0.47 ± 0.08, C 0.34 ± 0.04; bone-implant contact : UVC-1/6 hour 84.30 ± 5.02%, UVC-1/2 hour 85.82 ± 5.05%, and UVC-1 hour 84.98 ± 3.86%, C 71.69 ± 3.52%. P < .05), whereas, no significant difference was observed among the UVC groups. At 12 weeks, there were no significant differences between the C group and UVC groups. After 4 and 12 weeks of healing, no significant difference in implant stability quotient values was observed between the C group and UVC groups. CONCLUSIONS: UVC photofunctionalization improved the early osseointegration of aged titanium implants. However, the effect was not dependent on the UVC-light duration within the range from 1/6 hour to 1 hour.

Analysis of the Relationship Between Periampullary Diverticulum and Recurrent Bile Duct Stones After Endoscopy on Magnetic Resonance Imaging of Magnetic Nanoparticles.

The objective of this work was to investigate the effect of magnetic resonance cholangiopancreatography (MRCP) based on super-paramagnetic iron oxide nanoparticles (SPIONs) on the recurrence diagnosis of periampullary diverticulum (PAD) and bile duct stone (BDS), so as to provide a scientific research basis for the recidivation factors of bile duct stones in clinic. Patients with PAD diagnosed in hospital from July 2019 to March 2021 (who had undergone endoscopic gallstone surgery) were selected for study in this work. They were rolled into two groups, the parapapillary group (123 cases) and the cholangiopancreatic duct directly opening in the diverticulum group (97 cases), according to the clinical classification. Then, 100 patients without PAD who had undergone bile duct node therapy were selected as the control group. The recidivation of BDS, serological index, and biliary pressure index before and after treatment were compared. The relationship between PAD and recidivation of bile duct stones was analyzed. The results showed that the average particle size, hydration kinetic particle size, effective time, and duration of polyethylene glycol (PEG)/polyethyleneimine (PEI)/poly aspartic acid-super-paramagnetic iron oxide nanoparticles(PASP-SPIONs) were better than PEG/PEI-SPIONs and SPIONs. The recidivation rate of BDS in Groups R and X was remarkably higher than the rate in control group (P < 0.05). Before treatment, common bile duct pressure in the control group was lower obviously than that in Groups R and X (P < 0.05). After treatment, the indexes including total bilirubin, direct bilirubin, and alkaline phosphatase in control group were lower than those in Groups R and X (P < 0.05). The incidence of complications in Groups R and X was much higher than in contrast to the control group (P < 0.05). Therefore, PEG/PEI/PASP-SPIONs had good contrast effect and could be used as magnetic resonance imaging contrast agent. Complications such as common bile duct pressure and infection were increased by PAD, which may be the main factor for the recidivation of BDS.

A digital workflow for the fabrication of an immediate implant-supported interim restoration.

Immediate interim restorations in the esthetic region are usually fabricated in situ by using the pick-up technique, which is time-consuming and has a potential for cross-infection. This article describes a rapid and precise workflow for the fabrication of an immediate implant-supported interim restoration. A cast with gingival contours and an extended tube to accommodate the implant analogs is generated preoperatively based on the virtual implant planning and a predesigned restoration. After guided osteotomy and implant insertion, the actual three-dimensional (3D) implant position is transferred precisely from the mouth to the printed cast by using the surgical guide. This technique can achieve the rapid and precise fabrication of the interim restoration with guidance immediately after the surgery, decreasing the risk of cross-infection and reducing clinical steps and time.

A digital workflow for accurately and rapidly creating an immediate provisional restoration with natural emergence profile using extracted tooth.

To describe a digital workflow for creating a provisional restoration by using an extracted tooth rapidly, finally fixing the provisional restoration in the targeted position precisely and preserving the natural emergence profile from the time of provisional restoration to final restoration. CLINICAL CONSIDERATIONS: The use of extracted tooth as an immediate provisional restoration is an effective method for preserving the shape of the emergence profile. However, the existing methods for creating a provisional restoration by using natural tooth are time-consuming and there is no reliable method to precisely attach tooth to temporary abutment. This case demonstrates a new method for using patient's natural tooth as an immediate provisional restoration under a sequence of guides, which significantly reduces the chair-side time and inconvenience for clinicians and patients. Immediate provisional restoration contributes to preserving the soft tissue architecture after post-extraction implant placement, especially when using the patient's tooth as a provisional restoration. Digital technology can help to improve the chair-side clinical efficiency of dentist. CLINICAL SIGNIFICANCE: Maintaining the natural soft tissue architecture is a huge challenge in dental implantology. Use of the extracted tooth as a provisional restoration is likely to achieve an optimal outcome. And digital technology is helpful to the efficiency and accuracy of treatment.

FGD5­AS1 is an oncogenic lncRNA in pancreatic cancer and regulates the Wnt/ß­catenin signaling pathway via miR­577.

The objective of the present study was to clarify the expression characteristics of long non­coding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5­AS1) in pancreatic cancer, as well as its biological function and underlying mechanism. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was utilized for the detection of FGD5­AS1 and microRNA (miR)­577 expression levels in pancreatic cancer tissues. Transfection was performed to upregulate or downregulate FGD5­AS1 in pancreatic cancer cell lines. MTT and Transwell assays were then utilized to detect the proliferation, migration and invasion of cancer cells, respectively. Subsequently, dual­luciferase reporter gene assay, RNA immunoprecipitation assay, RNA pull­down assay, RT­qPCR, western blotting, and Pearson's correlation analysis were employed to confirm the regulatory relationships among FGD5­AS1, miR­577, low­density lipoprotein receptor­related protein 6 (LRP6) and ß­catenin. Western blotting was employed to determine the expression levels of Axin2, cyclin D1 and c­Myc. The expression level of FGD5­AS1 was upregulated in pancreatic cancer tissues and cell lines. FGD5­AS1 knockdown inhibited pancreatic cancer cell proliferation, migration and invasion. By contrast, miR­577 was significantly inhibited in pancreatic cancer cells and tissues; its downregulation promoted pancreatic cancer cell proliferation, migration and invasion, and reversed the effects of FGD5­AS1 knockdown on pancreatic cancer cells. In addition, it was revealed that miR­577 was a target of FGD5­AS1, and FGD5­AS1 could modulate the expression levels of LRP6, ß­catenin, Axin2, cyclin D1 and c­Myc via suppressing miR­577. In conclusion, in pancreatic cancer, highly expressed FGD5­AS1 activated the Wnt/ß­catenin signaling and promoted cancer cell proliferation, migration and invasion via suppression of miR­577.