Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial.

BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Biomaterials with cancer cell-specific cytotoxicity: challenges and perspectives.

Significant advances have been made in materials for biomedical applications, including tissue engineering, bioimaging, cancer treatment, etc. In the past few decades, nanostructure-mediated therapeutic strategies have been developed to improve drug delivery, targeted therapy, and diagnosis, maximizing therapeutic effectiveness while reducing systemic toxicity and side effects by exploiting the complicated interactions between the materials and the cell and tissue microenvironments. This review briefly introduces the differences between the cells and tissues of tumour or normal cells. We summarize recent advances in tumour microenvironment-mediated therapeutic strategies using nanostructured materials. We then comprehensively discuss strategies for fabricating nanostructures with cancer cell-specific cytotoxicity by precisely controlling their composition, particle size, shape, structure, surface functionalization, and external energy stimulation. Finally, we present perspectives on the challenges and future opportunities of nanotechnology-based toxicity strategies in tumour therapy.

Superoxide dismutase 1-modified dental pulp stem cells alleviate high-altitude pulmonary edema by inhibiting oxidative stress through the Nrf2/HO-1 pathway.

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

Synthesis and Properties of Bright Red-to-NIR BODIPY Dyes for Targeting Fluorescence Imaging and Near-Infrared Photothermal Conversion.

An efficient synthesis of 3-pyrrolylBODIPY dyes has been developed from a rational mixture of various aromatic aldehydes and pyrrole in a straightforward condensation reaction, followed by in situ successively oxidative nucleophilic substitution using a one-pot strategy. These resultant 3-pyrrolylBODIPYs without blocking substituents not only exhibit the finely tunable photophysical properties induced by the flexible meso-aryl substituents but also serve as a valuable synthetic framework for further selective functionalization. As a proof of such potential, one 3-pyrrolylBODIPY dye (581/603 nm) through the installation of the morpholine group is applicable for lysosome-targeting imaging. Furthermore, an ethene-bridged 3,3'-dipyrrolylBODIPY dimer was constructed, which displayed a near-infrared (NIR) emission extended to 1200 nm with a large fluorescence brightness (2840 M-1 cm-1). The corresponding dimer nanoparticles (NPs) afforded a high photothermal conversion efficiency (PCE) value of 72.5%, eventually resulting in favorable photocytotoxicity (IC50 = 9.4 µM) and efficient in vitro eradication of HeLa cells under 808 nm laser irradiation, highlighting their potential application for photothermal therapy in the NIR window.

Porphyromonas gingivalis OMVs promoting endothelial dysfunction via the STING pathway in periodontitis.

OBJECTIVE: This study aimed to assess the effects of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs) in chronic periodontitis and explore the underlying mechanism involved. METHODS: In vitro, Pg-OMVs were incubated with Ea.hy926 (vessel endothelial cells, ECs) to evaluate their effects on endothelial functions and to investigate the underlying mechanism. The effects of endothelial dysfunction on MG63 osteoblast-like cells were verified using an indirect co-culture method. For in vivo studies, micro-CT was conducted to identify alveolar bone mass. Immunofluorescence staining was conducted to confirm the levels of stimulator of interferon genes (STING) in the blood vessel and the number of Runx2+ cells around the alveolar bone. RESULTS: Pg-OMVs were endocytosed by ECs, leading to endothelial dysfunction. The cGAS-STING-TBK1 pathway was activated in ECs, which subsequently inhibited MG63 migration and early osteogenesis differentiation. In vivo, Pg-OMVs promoted alveolar bone resorption, increased STING levels in the blood vessel, and decreased Runx2+ cells around the alveolar bone. CONCLUSIONS: Pg-OMVs caused endothelial dysfunction and activated the cGAS-STING-TBK1 signal cascade in ECs, thereby impairing ECs-mediated osteogenesis. Furthermore, Pg-OMVs aggregated alveolar bone loss and altered the blood vessel-mediated osteogenesis with elevated STING.

IFT80 promotes early bone healing of tooth sockets through the activation of TAZ/RUNX2 pathway.

Intraflagellar transport (IFT) proteins have been reported to regulate cell growth and differentiation as the essential functional component of primary cilia. The effects of IFT80 on early bone healing of extraction sockets have not been well studied. To investigate whether deletion of Ift80 in alveolar bone-derived mesenchymal stem cells (aBMSCs) affected socket bone healing, we generated a mouse model of specific knockout of Ift80 in Prx1 mesenchymal lineage cells (Prx1Cre ;IFT80f/f ). Our results demonstrated that deletion of IFT80 in Prx1 lineage cells decreased the trabecular bone volume, ALP-positive osteoblastic activity, TRAP-positive osteoclastic activity, and OSX-/COL I-/OCN-positive areas in tooth extraction sockets of Prx1Cre ; IFT80f/f mice compared with IFT80f/f littermates. Furthermore, aBMSCs from Prx1Cre ; IFT80f/f mice showed significantly decreased osteogenic markers and downregulated migration and proliferation capacity. Importantly, the overexpression of TAZ recovered significantly the expressions of osteogenic markers and migration capacity of aBMSCs. Lastly, the local administration of lentivirus for TAZ enhanced the expression of RUNX2 and OSX and promoted early bone healing of extraction sockets from Prx1Cre ; IFT80f/f mice. Thus, IFT80 promotes osteogenesis and early bone healing of tooth sockets through the activation of TAZ/RUNX2 pathway.

Temporal gene expression profiling during early-stage traumatic temporomandibular joint bony ankylosis in a sheep model.

BACKGROUND: Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. METHODS: Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. RESULTS: Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. CONCLUSIONS: These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.

Roles of trained immunity in the pathogenesis of periodontitis.

Periodontitis is a chronic, inflammatory, and destructive disease caused by the imbalance of host immune response and dental biofilm, and has strong epidemiological and pathogenesis correlations with systemic diseases. The immune response in periodontitis involves both innate and adaptive immunity, with numerous immune cells and inflammatory pathways participating in a complex network of interactions. In the past decade, the concept of "trained immunity" has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. There is growing interest in exploring the role of trained immunity in chronic inflammatory and metabolic diseases such as atherosclerosis and diabetes mellitus. Evidence suggests that trained immunity may also regulate the onset and progression of periodontitis, serving as a bridge between periodontitis-related comorbidities. In this review, we summarize concepts related to trained immunity and its development. Furthermore, we present current evidence that endorses the notion of trained immunity in periodontitis and analyze possible roles it may assume regarding periodontitis-associated inflammatory reactions from a cellular perspective. Finally, we discuss various clinical therapeutic strategies for periodontitis and its associated comorbidities that target trained immunity. We hope that more researchers will pay attention to this emerging concept, thereby providing deeper insights into this novel field.

Changes of maxillary central incisor and alveolar bone in Class II Division 2 nonextraction treatment with a fixed appliance or clear aligner: A pilot cone-beam computed tomography study.

INTRODUCTION: This retrospective clinical study investigated the clinical changes of maxillary central incisor and alveolar bone in Class II Division 2 nonextraction treatment with fixed appliances or clear aligners on the basis of cone-beam computed tomography. METHODS: Fifty-nine Chinese Han patients with similar demographic characteristics were collected from a conventional bracket group, a self-ligating bracket group, and a clear aligner group. All measurements about root resorption and alveolar bone thickness on the cone-beam computed tomography images were tested. Changes between pretreatment and posttreatment were evaluated by paired-sample t test. The variation among the 3 groups was compared by 1-way analysis of variance. RESULTS: The resistance center of the maxillary central incisor showed upward or forward movement, and the axial inclination was increased in 3 groups (P <0.0001). Root volume loss in the clear aligner group (23.68 ± 4.82 mm3) was significantly less than that in the fixed appliances group (28.24 ± 6.44 mm3 in the conventional bracket group, 28.17 ± 6.07 mm3 in the self-ligating bracket group) (P <0.05). All 3 groups showed a significant decrease in palatal alveolar bone and total bone thickness at all 3 levels at posttreatment. In contrast, labial bone thickness significantly increased except for crestal level l. Among the 3 groups, the clear aligner group had a prominent increase in labial bone thickness at the apical level (P = 0.0235). CONCLUSIONS: Clear aligner treatment for Class II Division 2 malocclusions could effectively reduce the incidence of fenestration and root resorption. Our findings will be beneficial to comprehensively understand the effectiveness of different appliances for Class II Division 2 malocclusions treatment.

[Efficacy analysis of autologous facet joint bone block in lumbar interbody fusion of osteoporosis patients].

OBJECTIVE: To compare and analyze the feasibility of autologous facet joint bone block as an alternative to polyetheretherketone (PEEK) cage in lumbar intervertebral fusion surgery for patients with osteoporosis. METHODS: From December 2018 to June 2021, the case data of patients with osteoporosis (T value ≤ -2.5 on dual energy X-ray bone density) who underwent posterior lumbar interbody fusion in the Fourth Medical Center, Chinese PLA General Hospital were retrospectively reviewed. All the cases were followed up for no less than 12 months and were divided into two groups according to the differences of interbody fusion materials: the autologous facet joint bone block group (autogenous bone group) and the PEEK cage group (PEEK group). The general data [such as age, gender, body mass index (BMI), primary diagnosis, distribution of fusion segments, bone mineral density of lumbar (BMD), incidence of preoperative complications], the perioperative data (such as duration of operation, intraoperative blood loss, postoperative drainage, perioperative allogeneic blood transfusion rate), and the incidence of postoperative complications were compared between the two groups. Imaging parameters (disc height, lumbar lordosis angle, segment lordosis angle, segmental lordosis angle, disc height improvement rate, and fusion rate) and lumbar functional scores [visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedics Association (JOA) score for lower back pain] were compared to evaluate the clinical efficacy between the kinds of intervertebral fusion materials 1 week, 3 months and 6 months postoperative and at the last follow-up. RESULTS: A total of 118 patients were enrolled, including 68 cases in the autogenous bone group and 50 cases in the PEEK group, there were no statistical differences in age, gender, BMI, primary diagnosis, distribution of fusion segments, BMD, incidence of preoperative complications, duration of operation, intraoperative blood loss, postoperative drainage, perioperative allogeneic blood transfusion rate, incidence of postoperative complications, all the preoperative imaging parameters and all the lumbar function scores between the two groups (P>0.05). Postoperative superficial surgical site infections occurred in 3 patients in the autogenous bone group and 2 patients in the PEEK group. At the last follow-up, 3 cases of intervertebral graft collapse occurred in the autogenous bone group and 5 cases in the PEEK group, 1 case of graft subsidence in the autogenous bone group and 1 case in the PEEK group. All the imaging parameters showed significant differences between postoperation and preoperation (P < 0.05), and all the imaging parameters showed significant differences between 1 week and 3 months postoperative in both groups (P < 0.05). The height, angle of fusion gap in the autogenous bone group were lower than those in the PEEK group 1 week postoperatively (P < 0.05), and the fusion gap height improvement rate in the autogenous bone group was lower than that in the PEEK group (P < 0.05). The cases in both groups started to show final fusion 3 months after surgery, and the fusion rate in the autogenous bone group was 75% 6 months postoperatively, which was significantly higher than the rate of 56% in the PEEK group (P < 0.05), and there was no statistically significant difference in the final fusion rate between the two groups (P>0.05). The ODI, the postoperative VAS score was significantly lower than that in preoperation, while the postoperative JOA score was significantly higher than that in preoperation (P < 0.05). The ODI was lower while the JOA score was higher of the autogenous bone group than that of the PEEK group 6 months postoperatively (P < 0.05). CONCLUSION: In osteoporosis patients, good interbody fusion rate and improvement of lumbar vertebral function can be obtained by using autologous facet joint bone block or PEEK cage, while the fusion rate and the improvement of lumbar function with autologous facet joint bone block are better than those with PEEK cage 6 months post-operatively. PEEK cage is superior to autologous facet joint bone block in intervertebral distraction and improvement of lumbar lordosis. Significant disc space subsidence occurred in osteoporotic patients within 3 months after lumbar interbody fusion, and the subsidence of PEEK cage was more obvious than that of autologous facet joint bone block.

Recombinase polymerase amplification assay for rapid detection of Seneca Valley Virus.

Seneca Valley virus (SVV) is related to vesicular disease in pigs, and its clinical symptoms are indistinguishable from other notifiable clinical symptoms of vesicular disease such as foot-and-mouth disease. The rapid and accurate detection of SVV is essential to confirm the pathogenic factors and initiate the implementation of control measures. The development of a rapid, simple, convenient, and low-cost molecular (nucleic acid amplification) test that can be used at the sample collection point has been identified as a key component for controlling SVV. This study describes the development and demonstration of recombinase polymerase amplification (RPA) test targeting the conserved regions of SVV for detection of SVV. The Primers and probes designed by us have shown good sensitivity and specificity in RPA test, which is helpful for RPA to be an effective tool for rapid diagnosis of SVV.

Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury.

Stem cell-derived exosomes have recently been regarded as potential drugs for treating spinal cord injury (SCI) by reducing reactive oxygen species (ROS) and suppressing M1 macrophage polarization. However, the roles of ROS and exosomes in the process of M1 macrophage polarization are not known. Herein, we demonstrated that ROS can induce M1 macrophage polarization and have a concentration-dependent effect. ROS can induce M1 macrophage polarization through the MAPK-NFκB P65 signaling pathway. Dental pulp stem cell (DPSC)-derived exosomes can reduce macrophage M1 polarization through the ROS-MAPK-NFκB P65 signaling pathway in treating SCI. This study suggested that DPSC-derived exosomes might be a potential drug for treating SCI. Disruption of the cycle between ROS and M1 macrophage polarization might also be a potential effective treatment by reducing secondary damage.

Dynamic Change in Oral Microbiota of Children With Cleft Lip and Palate After Alveolar Bone Grafting.

To investigate the longitudinal influence of alveolar bone grafting on the oral microbiota of children with cleft lip and palate (CLP).Twenty-eight children with nonsyndromic CLP were recruited and underwent secondary alveolar bone grafting at the first time. Unstimulated saliva and plaque samples were collected from the subjects preoperatively and at 2 days, 1 month, and 3 months postoperatively. The v3-v4 hypervariable regions of the 16S rRNA gene from bacterial DNA were sequenced using the Illumina MiSeq sequencing platform.The alpha diversity of the saliva and plaque microbiota was significantly decreased at 2 days postoperatively and then increased at 1 and 3 months postoperatively. The saliva and plaque microbiota compositions at 2 days postoperatively differed from those at the other time points, and the microbiota compositions at 1 and 3 months postoperatively showed a gradual shift toward the preoperative composition. The saliva, but not plaque, microbiota composition 3 months postoperatively was similar to that preoperatively.The effect of secondary alveolar bone grafting on the plaque microbiota in children with CLP lasted longer than the saliva microbiota. Alveolar bone grafting altered the saliva microbiota in children with CLP within 3 months postoperatively.

Dysfunction of the 4-coumarate:coenzyme A ligase 4CL4 impacts aluminum resistance and lignin accumulation in rice.

The root cell wall is the first and primary target of aluminum (Al) toxicity. Monocots such as rice (Oryza sativa) can accumulate appreciable levels of hydroxycinnamic acids (HCAs) to modify and cross-link hemicellulose and/or lignin of the cell wall. Nevertheless, it is unclear whether this HCA-mediated modification of the cell wall is important for Al accumulation and resistance. We previously isolated and characterized a rice ral1 (resistance to aluminum 1) mutant that shows enhanced Al resistance. In this study, we cloned RAL1 and found that it encodes the 4-coumarate:coenzyme A ligase 4CL4, an enzyme putatively involved in lignin biosynthesis. Mutation of RAL1/4CL4 reduces lignin content and increases the accumulation of its substrates 4-coumaric acid (PA) and ferulic acid (FA). We demonstrate that altered lignin accumulation is not required for the enhanced Al resistance in ral1/4cl4 mutants. We found that the increased accumulation of PA and FA can reduce Al binding to hemicellulose and consequently enhance Al resistance in ral1/4cl4 mutants. Al stress is able to trigger PA and FA accumulation, which is likely caused by the repression of the expression of RAL1/4CL4 and its homologous genes. Our results thus reveal that Al-induced PA and FA accumulation is actively and positively involved in Al resistance in rice through the modification of the cell wall and thereby the reduced Al binding to the cell wall.

Ultralow Resistance Two-Stage Electrostatically Assisted Air Filtration by Polydopamine Coated PET Coarse Filter.

Airborne particulate matters (PM) pose serious health threats to the population, and efficient filtration is needed for indoor and vehicular environments. However, there is an intrinsic conflict between filtration efficiency, air resistance, and service life. In this study, a two-stage electrostatically assisted air (EAA) filtration device is designed and the efficiency-air resistance-filter life envelope is significantly improved by a thin coating of polydopamine (PDA) on the polyethylene terephthalate (PET) coarse filter by in situ dopamine polymerization. The 8 mm thick EAA PDA-140@PET filter has a high filtration efficiency of 99.48% for 0.3 µm particles, low air resistance of 9.5 Pa at a filtration velocity of 0.4 m s-1 , and steady performance up to 30 d. Compared with the bare PET filter, the penetration rate for 0.3 µm particles is lowered by 20×. The coated PDA is of submicron thickness, 10-3  × the gap distance between filter fibers, so low air resistance could be maintained. The filter shows steadily high filtration efficiency and an acceptable increase of air resistance and holds nearly as many particles as its own weight in a 30 day long-term test. The working mechanism of the EAA coarse filter is investigated, and the materials design criteria are proposed.

A randomized comparison of two paclitaxel-coated balloons for the treatment of in-stent restenosis: The LONGTY ISR China randomized trial (LONGTY DCB vs. SeQuent Please DCB).

OBJECTIVES: This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR). BACKGROUND: Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB. METHODS: This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up. RESULTS: A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority <.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups. CONCLUSIONS: In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.

Effect of VEGFC on lymph flow and inflammation-induced alveolar bone loss.

The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+ /podoplanin (PDPN)+ lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+ /alpha-smooth muscle actin (αSMA)- lymphatic capillaries are increased, whereas PDPN+ /αSMA+ collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ /αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ /αSMA- lymphatic capillaries are increased, whereas LYVE1+ /αSMA+ collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation-mediated alveolar bone loss. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Current status survey of the extramural hospital management of venous thromboembolism after total hip and knee arthroplasty in China.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication after arthroplasty. Numerous prophylactic strategies and studies to reduce VTEs have focused on the duration of the hospital stay and on few extramural hospitals. This study aimed to investigate extramural hospital management of VTE after total hip/knee arthroplasty (THA/TKA) in China with a novel survey tool. METHODS: A total of 180 patients undergoing arthroplasty, including 68 THA patients and 112 TKA patients, were enrolled in this study. All patients received anticoagulant treatment management. A survey querying VTE management and adherence, such as therapy information, understanding of anticoagulation, satisfaction with the ability of medical staff, and satisfaction with health care costs, was administered by a questionnaire (TKA/THA Patients' Experience with Anticoagulation in the Post-discharge Period) for quality improvement. RESULTS: The average age of the patients was 65.27 ± 13.62 years. All patients knew their follow-up times. 85 % of them were suggested that re-examine at the next 14 days, and the others at the next 28 days. All patients continued to visit the orthopaedic clinic after discharge without choosing other types of outpatient services, such as an anticoagulant clinic or home visit with a nurse/pharmacist or remote evaluation by telephone. A total of 96.6 % of all patients used new oral anticoagulants, and the most common treatment duration was 2-4 weeks (93.3 %). 48 % informed their physicians that they were taking anticoagulation medications when they visited ophthalmology, dentistry, dermatology, and other departments. The overall rate of satisfaction with anticoagulation management was 81.67 %, and 6.67 % of patients were not unsatisfied with their medical expenses. Patient compliance decreased with increasing follow-up time. Continuous follow-ups after discharge significantly improved patient compliance. CONCLUSIONS: These results elucidate how we can improve the quality of anticoagulation. Continuous follow-up appointments for 30 days after discharge, especially for individuals over 65 years old, significantly improved patient satisfaction and reduced the incidence of VTE and medical costs.

ROCK-TAZ signaling axis regulates mechanical tension-induced osteogenic differentiation of rat cranial sagittal suture mesenchymal stem cells.

Mechanical force across sutures is able to promote suture osteogenesis. Orthodontic clinics often use this biological characteristic of sutures to treat congenital cranio-maxillofacial malformations. However, the underlying mechanisms still remain poorly understood. Craniofacial sutures provide a special growth source and support primary sites of osteogenesis. Here, we isolated rat sagittal suture cells (rSAGs), which had mesenchymal stem cell characteristics and differentiating abilities. Cells were then subjected to mechanical tension (5% elongation, 0.5 Hz; sinusoidal waveforms) showing that mechanical tension could enhance osteogenic differentiation but hardly affect proliferation of rSAGs. Besides, mechanical tension could increase Rho-associated kinase (ROCK) expression and enhance transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation. Inhibiting ROCK expression could suppress tension-induced osteogenesis and block tension-induced upregulation of nuclear TAZ. In addition, our results indicated that TAZ had direct combination sites with runt-related transcription factor 2 (Runx2) in rSAGs, and knock-downed TAZ simultaneously decreased the expression of Runx2 no matter with or without mechanical tension. In summary, our findings demonstrated that the multipotency of rSAGs in vitro could give rise to early osteogenic differentiation under mechanical tension, which was mediated by ROCK-TAZ signal axis.

Pegaspargase Combined with Concurrent Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Two-Center Phase II Study.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is expected to improve local and systemic disease control and has been established as a standard therapy for several types of solid tumors. Considering the benefits of frontline radiation and pegaspargase in localized extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL), we conducted a phase II study on pegaspargase-based CCRT to explore an effective treatment. MATERIALS AND METHODS: In this study, 30 patients with newly diagnosed nasal ENKTL in stages IE to IIE received CCRT (radiation 50 Gy and two cycles of pegaspargase 2,500 unit/m2 every 3 weeks). Four courses of pegaspargase were performed after CCRT. RESULTS: The patients completed CCRT and four cycles of pegaspargase. The complete remission (CR) rate was 90%, with a 95% confidential interval (CI) of 73.5%-97.9% after CCRT. The CR rate was 100% (95% CI, 88.4%-100%) at the end of the treatment. The 2-year overall survival and progression-free survival rates were 90.9% (95% CI, 78.4%-100%) and 92.8% (95% CI, 83.2%-100%), respectively. The major adverse events were in grades 1-2. CONCLUSION: Preliminary data indicate that pegaspargase combined with concurrent radiotherapy for newly diagnosed patients with nasal ENKTL was efficacious and well tolerated. Registered at www.chictr.org. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-OIC-15007662. IMPLICATIONS FOR PRACTICE: This clinical trial, evaluating the efficacy and toxicity of concurrent chemoradiotherapy by using single-drug pegaspargase for patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) in stage IE to IIE, showed pegaspargase combined with concurrent radiotherapy was efficacious and well tolerated. Pegaspargase has a long half-life and is easy to administer via intramuscular injection. Consequently, pegaspargase combined with concurrent radiotherapy for patients with ENKTL can be completed in the outpatient clinic.