Third Affiliated Hospital of Southern Medical University

Cancer-derived exosomes are considered a major driver of cancer-induced pre-metastatic niche formation at foreign sites, but the mechanisms remain unclear. Here, we show that miR-25-3p, a metastasis-promoting miRNA of colorectal cancer (CRC), can be transferred from CRC cells to endothelial cells via exosomes. Exosomal miR-25-3p regulates the expression of VEGFR2, ZO-1, occludin and Claudin5 in endothelial cells by targeting KLF2 and KLF4, consequently promotes vascular permeability and angiogenesis. In addition, exosomal miR-25-3p from CRC cells dramatically induces vascular leakiness and enhances CRC metastasis in liver and lung of mice. Moreover, the expression level of miR-25-3p from circulating exosomes is significantly higher in CRC patients with metastasis than those without metastasis. Our work suggests that exosomal miR-25-3p is involved in pre-metastatic niche formation and may be used as a blood-based biomarker for CRC metastasis.

BACKGROUND: Chronic kidney disease is an important cause of global mortality and morbidity. Data for epidemiological features of chronic kidney disease and its risk factors are limited for low-income and middle-income countries. The International Society of Nephrology's Kidney Disease Data Center (ISN-KDDC) aimed to assess the prevalence and awareness of chronic kidney disease and its risk factors, and to investigate the risk of cardiovascular disease, in countries of low and middle income. METHODS: We did a cross-sectional study in 12 countries from six world regions: Bangladesh, Bolivia, Bosnia and Herzegovina, China, Egypt, Georgia, India, Iran, Moldova, Mongolia, Nepal, and Nigeria. We analysed data from screening programmes in these countries, matching eight general and four high-risk population cohorts collected in the ISN-KDDC database. High-risk cohorts were individuals at risk of or with a diagnosis of either chronic kidney disease, hypertension, diabetes, or cardiovascular disease. Participants completed a self-report questionnaire, had their blood pressure measured, and blood and urine samples taken. We defined chronic kidney disease according to modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria; risk of cardiovascular disease development was estimated with the Framingham risk score. FINDINGS: 75,058 individuals were included in the study. The prevalence of chronic kidney disease was 14·3% (95% CI 14·0-14·5) in general populations and 36·1% (34·7-37·6) in high-risk populations. Overall awareness of chronic kidney disease was low, with 409 (6%) of 6631 individuals in general populations and 150 (10%) of 1524 participants from high-risk populations aware they had chronic kidney disease. Moreover, in the general population, 5600 (44%) of 12,751 individuals with hypertension did not know they had the disorder, and 973 (31%) of 3130 people with diabetes were unaware they had that disease. The number of participants at high risk of cardiovascular disease, according to the Framingham risk score, was underestimated compared with KDIGO guidelines. For example, all individuals with chronic kidney disease should be considered at high risk of cardiovascular disease, but the Framingham risk score detects only 23% in the general population, and only 38% in high-risk cohorts. INTERPRETATION: Prevalence of chronic kidney disease was high in general and high-risk populations from countries of low and middle income. Moreover, awareness of chronic kidney disease and other non-communicable diseases was low, and a substantial number of individuals who knew they were ill did not receive treatment. Prospective programmes with repeat testing are needed to confirm the diagnosis of chronic kidney disease and its risk factors. Furthermore, in general, health-care workforces in countries of low and middle income need strengthening. FUNDING: International Society of Nephrology.

PURPOSE: Chronic refractory wounds are a multifactorial comorbidity of diabetes mellitus with the characteristic of impaired vascular networks. Currently, there is a lack of effective treatments for such wounds. Various types of mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to exert multiple therapeutic effects on skin regeneration. We aimed to determine whether a constructed combination of human umbilical cord MSC (hUCMSC)-derived exosomes (hUCMSC-exos) and Pluronic F-127 (PF-127) hydrogel could improve wound healing. MATERIALS AND METHODS: We topically applied human umbilical cord-derived MSC (hUCMSC)-derived exosomes (hUCMSC-exos) encapsulated in a thermosensitive PF-127 hydrogel to a full-thickness cutaneous wound in a streptozotocin-induced diabetic rat model. The material properties and wound healing ability of the hydrogel and cellular responses were analyzed. RESULTS: Compared with hUCMSC-exos, PF-127-only or control treatment, the combination of PF-127 and hUCMSC-exos resulted in a significantly accelerated wound closure rate, increased expression of CD31 and Ki67, enhanced regeneration of granulation tissue and upregulated expression of vascular endothelial growth factor (VEGF) and factor transforming growth factor beta-1 (TGFβ-1). CONCLUSION: The efficient delivery of hUCMSC-exos in PF-127 gel and improved exosome ability could promote diabetic wound healing. Thus, this biomaterial-based exosome therapy may represent a new therapeutic approach for cutaneous regeneration of chronic wounds.

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue-like electroconductive hydrogels loaded with BMSC-exosomes are developed for the synergistic treatment of SCI. These exosomes-loaded electroconductive hydrogels modulate microglial M2 polarization via the NF-κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68-positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC-exosomes is a promising therapeutic strategy for SCI repair.

BACKGROUND: Intracerebral hemorrhage (ICH) induces potently oxidative stress responses and inflammatory processes. Isoliquiritigenin (ILG) is a flavonoid with a chalcone structure and can activate nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant system, negatively regulate nuclear factor-κB (NF-κB) and nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathways, but its role and potential molecular mechanisms in the pathology following ICH remain unclear. The present study aimed to explore the effects of ILG after ICH and underlying mechanisms. METHODS: ICH model was induced by collagenase IV (0.2 U in 1 μl sterile normal saline) in male Sprague-Dawley rats weighing 280-320 g. Different doses of ILG (10, 20, or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling, respectively. Rats were intracerebroventricularly administrated with control scramble small interfering RNA (siRNA) or Nrf2 siRNA at 24 h before ICH induction, and after 24 h, ICH model was established with or without ILG (20 mg/kg) treatment. All rats were dedicated at 24 or 72 h after ICH. Neurological deficits, histological damages, brain water content (BWC), blood-brain barrier (BBB) disruption, and neuronal degeneration were evaluated; quantitative real-time RT-PCR (qRT-PCR), immunohistochemistry/immunofluorescence, western blot, and enzyme-linked immunosorbent assay (ELISA) were carried out; catalase, superoxide dismutase activities and reactive oxygen species (ROS), and glutathione/oxidized glutathione contents were measured. RESULTS: ILG (20 and 40 mg/kg) markedly alleviated neurological deficits, histological damages, BBB disruption, brain edema, and neuronal degeneration, but there was no significant difference between two dosages. ILG (20 mg/kg) significantly suppressed the NF-κB and NLRP3 inflammasome pathways and activated Nrf2-mediated antioxidant system. Gene silencing of Nrf2 aggravated the neurological deficits, brain edema, and neuronal degeneration and increased the protein levels of NF-κB p65, NLRP3 inflammasome components, and IL-1β. ILG delivery significantly attenuated the effects of Nrf2 siRNA interference mentioned above. CONCLUSIONS: Intraperitoneal administration of ILG after ICH reduced early brain impairments and neurological deficits, and the mechanisms were involved in the regulation of ROS and/or NF-κB on the activation of NLRP3 inflammasome pathway by the triggering of Nrf2 activity and Nrf2-induced antioxidant system. In addition, our experimental results may make ILG a potential candidate for a novel therapeutical strategy for ICH.

A switch from autophagy to apoptosis is implicated in chondrocytes during the osteoarthritis (OA) progression with currently unknown mechanism(s). In this study we utilized a flow fluid shear stress (FFSS) model in cultured chondrocytes and a unilateral anterior crossbite (UAC) animal model. We found that both FFSS and UAC actively induced endoplasmic reticulum stress (ERS) in the temporomandibular joints (TMJ) chondrocytes, as demonstrated by dramatic increases in expression of HSPA5, p-EIF2AK3, p-ERN1 and ATF6. Interestingly, both FFSS and UAC activated not only pro-death p-EIF2AK3-mediated ERS-apoptosis programs but also pro-survival p-ERN1-mediated autophagic flux in chondrocytes. Data from FFSS demonstrated that MTORC1, a downstream of p-ERN1, suppressed autophagy but promoted p-EIF2AK3 mediated ERS-apoptosis. Data from UAC model demonstrated that at early stage both the p-ERN1 and p-EIF2AK3 were activated and MTORC1 was inhibited in TMJ chondrocytes. At late stage, MTORC1-p-EIF2AK3-mediated ERS apoptosis were predominant, while p-ERN1 and autophagic flux were inhibited. Inhibition of MTORC1 by TMJ local injection of rapamycin in rats or inducible ablation of MTORC1 expression selectively in chondrocytes in mice promoted chondrocyte autophagy and suppressed apoptosis, and reduced TMJ cartilage loss induced by UAC. In contrast, MTORC1 activation by TMJ local administration of MHY1485 or genetic deletion of Tsc1, an upstream MTORC1 suppressor, resulted in opposite effects. Collectively, our results establish that aberrant mechanical loading causes cartilage degeneration by activating, at least in part, the MTORC1 signaling which modulates the autophagy and apoptosis programs in TMJ chondrocytes. Thus, inhibition of MTORC1 provides a novel therapeutic strategy for prevention and treatment of OA.

Microcalcification is an effective indicator of early breast cancer. To improve the diagnostic accuracy of microcalcifications, this study evaluates the performance of deep learning-based models on large datasets for its discrimination. A semi-automated segmentation method was used to characterize all microcalcifications. A discrimination classifier model was constructed to assess the accuracies of microcalcifications and breast masses, either in isolation or combination, for classifying breast lesions. Performances were compared to benchmark models. Our deep learning model achieved a discriminative accuracy of 87.3% if microcalcifications were characterized alone, compared to 85.8% with a support vector machine. The accuracies were 61.3% for both methods with masses alone and improved to 89.7% and 85.8% after the combined analysis with microcalcifications. Image segmentation with our deep learning model yielded 15, 26 and 41 features for the three scenarios, respectively. Overall, deep learning based on large datasets was superior to standard methods for the discrimination of microcalcifications. Accuracy was increased by adopting a combinatorial approach to detect microcalcifications and masses simultaneously. This may have clinical value for early detection and treatment of breast cancer.

New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation-induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor-π-acceptor structure, this polymer shows a high reactive oxygen species (ROS)-generation ability compared to a low-mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated in vitro and in vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria-related infections in practical applications.

Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in IL-10-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is a fatal cardiovascular emergency requiring rapid reperfusion treatment. During the coronavirus disease-2019 (COVID-19) pandemic, medical professionals need to strike a balance between providing timely treatment for STEMI patients and implementing infection control procedures to prevent nosocomial spread of COVID-19 among health care workers and other vulnerable cardiovascular patients. OBJECTIVES: This study evaluates the impact of the COVID-19 outbreak and China Chest Pain Center's modified STEMI protocol on the treatment and prognosis of STEMI patients in China. METHODS: Based on the data of 28,189 STEMI patients admitted to 1,372 Chest Pain Centers in China between December 27, 2019 and February 20, 2020, the study analyzed how the COVID-19 outbreak and China Chest Pain Center's modified STEMI protocol influenced the number of admitted STEMI cases, reperfusion strategy, key treatment time points, and in-hospital mortality and heart failure for STEMI patients. RESULTS: The COVID-19 outbreak reduced the number of STEMI cases reported to China Chest Pain Centers. Consistent with China Chest Pain Center's modified STEMI protocol, the percentage of patients undergoing primary percutaneous coronary intervention declined while the percentage of patients undergoing thrombolysis increased. With an average delay of approximately 20 min for reperfusion therapy, the rate of in-hospital mortality and in-hospital heart failure increased during the outbreak, but the rate of in-hospital hemorrhage remained stable. CONCLUSIONS: There were reductions in STEMI patients' access to care, delays in treatment timelines, changes in reperfusion strategies, and an increase of in-hospital mortality and heart failure during the COVID-19 pandemic in China.

Multifunctional hydrogel with asymmetric and reversible adhesion characteristics is essential to handle the obstructions towards bioapplications of trauma removal and postoperative tissue synechia. Herein, we developed a responsively reversible and asymmetrically adhesive Janus hydrogel that enables on-demand stimuli-triggered detachment for efficient myocardial infarction (MI) repair, and synchronously prevents tissue synechia and inflammatory intrusion after surgery. In contrast with most irreversibly and hard-to-removable adhesives, this Janus hydrogel exhibited a reversible adhesion capability and can be noninvasively detached on-demand just by slight biologics. It is interesting that the adhesion behaves exhibited a molecularly encoded adhesion-adaptive stiffening feature similar to the self-protective stress-strain effect of biological tissues. In vitro and in vivo experiments demonstrated that Janus hydrogel can promote the maturation and functions of cardiomyocytes, and facilitate MI repair by reducing oxidative damage and inflammatory response, reconstructing electrical conduction and blood supply in infarcted area. Furthermore, no secondary injury and tissue synechia were triggered after transplantation of Janus hydrogel. This smart Janus hydrogel reported herein offers a potential strategy for clinically transformable cardiac patch and anti-postoperative tissue synechia barrier.

Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.

BACKGROUND: More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. RESULTS: Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. CONCLUSIONS: Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.

Anti-diabetic drug metformin has been shown to enhance osteoblasts differentiation and inhibit osteoclast differentiation in vitro and prevent bone loss in ovariectomized (OVX) rats. But the mechanisms through which metformin regulates osteoclastogensis are not known. Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. In this study, we demonstrated that metformin dose-dependently stimulated OPG and reduced RANKL mRNA and protein expression in mouse calvarial osteoblasts and osteoblastic cell line MC3T3-E1. Inhibition of AMP-activated protein kinase (AMPK) and CaM kinase kinase (CaMKK), two targets of metformin, suppressed endogenous and metformin-induced OPG secretion in osteoblasts. Moreover, supernatant of osteoblasts treated with metformin reduced formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in Raw264.7 cells. Most importantly, metformin significantly increased total body bone mineral density, prevented bone loss and decreased TRAP-positive cells in OVX rats proximal tibiae, accompanied with an increase of OPG and decrease of RANKL expression. These in vivo and in vitro studies suggest that metformin reduces RANKL and stimulates OPG expression in osteoblasts, further inhibits osteoclast differentiation and prevents bone loss in OVX rats.

To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

Background and Aims: The clinical efficacy of fecal microbiota transplantation (FMT) in patients with non-alcoholic fatty liver disease (NAFLD) and the variant effects of FMT on lean and obese NAFLD patients remain elusive. Our study aimed to determine the clinical efficacy and safety of FMT for patients with NAFLD, elucidating its different influences on lean and obese patients with NAFLD. Methods: colonoscopy, followed by three enemas over 3 days. Both groups were also required to maintain a healthy diet and keep regular exercise for more than 40 min every day. They returned to the hospital for reexamination 1 month after treatment. Results: FMT can decrease the fat accumulation in the liver by improving the gut microbiota dysbiosis, thus attenuating fatty liver disease. Significant differences in the clinical features and gut microbiota between lean and obese NAFLD patients were unveiled. Moreover, FMT had better effects on gut microbiota reconstruction in lean NAFLD than in obese NAFLD patients. Conclusions: FMT could successfully improve the therapeutic effects on patients with NAFLD, and its clinical efficacy was higher in lean NAFLD than in obese NAFLD patients.

BACKGROUND: The correct identification of pills is very important to ensure the safe administration of drugs to patients. Here, we use three current mainstream object detection models, namely RetinaNet, Single Shot Multi-Box Detector (SSD), and You Only Look Once v3(YOLO v3), to identify pills and compare the associated performance. METHODS: In this paper, we introduce the basic principles of three object detection models. We trained each algorithm on a pill image dataset and analyzed the performance of the three models to determine the best pill recognition model. The models were then used to detect difficult samples and we compared the results. RESULTS: The mean average precision (MAP) of RetinaNet reached 82.89%, but the frames per second (FPS) is only one third of YOLO v3, which makes it difficult to achieve real-time performance. SSD does not perform as well on the indicators of MAP and FPS. Although the MAP of YOLO v3 is slightly lower than the others (80.69%), it has a significant advantage in terms of detection speed. YOLO v3 also performed better when tasked with hard sample detection, and therefore the model is more suitable for deployment in hospital equipment. CONCLUSION: Our study reveals that object detection can be applied for real-time pill identification in a hospital pharmacy, and YOLO v3 exhibits an advantage in detection speed while maintaining a satisfactory MAP.

BACKGROUND: Macrophages are central players in the pathogenesis of periodontitis. However, the phenotypic switch of macrophage M1/M2 remains uncertain. METHODS: Adult male mice were divided into periodontitis (P) or control (C) groups. Bone marrow-derived macrophages (BMMs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). In both the periodontium and serum, macrophage M1 and M2 phenotypes were detected in vivo and in vitro via the following: 1) immunofluorescence; 2) immunohistochemistry; 3) electrochemiluminescence immunoassays; 4) quantitative polymerase chain reaction assays; and 5) enzyme-linked immunosorbent assays. The M1-type markers used included the following: 1) nitric oxide synthase (NOS)-2; 2) tumor necrosis factor-alpha; 3) interleukin (IL)-1β; 4) IL-6; and 5) C-reactive protein. The M2-type markers were as follows: 1) arginase-1; 2) cluster of differentiation (CD) 206; and 3) IL-10. RESULTS: Compared with the C group, the P group had a 14-fold increase in F4/80(+) NOS2(+) cells and four-fold more F4/80(+) CD206(+) cells with an enhanced NOS2/CD206 ratio in the periodontium (P <0.01). NOS2(-) CD206(+) and dual NOS2(+) CD206(+) macrophages dominated in the C and P groups, respectively. The P group had significantly increased M1- and M2-type cytokines in both the periodontium and serum and also had an enhanced IL-6/IL-10 ratio in the serum (P <0.05). M1-type markers were significantly upregulated at the mRNA level, whereas M2-type markers were downregulated at both the mRNA and protein levels in BMMs after LPS stimulation (P <0.01). CONCLUSION: Periodontal inflammation is associated with an enhancement of both the M1 and M2 phenotypes of macrophages, in which a phenotypic switch of M2 to M1 might be a critical mechanism in mediating periodontal tissue damage, including alveolar bone loss.

BACKGROUND: Whether white-coat hypertension (WCH) is an innocent phenomenon is controversial. METHOD: In this study, we evaluated the association of WCH and the risk of cardiovascular diseases (CVDs) and mortality, stratified by baseline antihypertensive treatment status. Databases (PubMed, EMBASE, CINAHL Plus, Scopus, and Google Scholar) were searched for prospective studies with data on CVD and total mortality associated with WCH. The primary outcomes were the risk of CVD and total mortality associated with WCH stratified by antihypertensive treatment status. The relative risks of events compared with normotension were calculated. RESULTS: A total of 23 cohorts (20 445 individuals), 11 cohorts (8656 individuals), and 12 cohorts (21 336 individuals) were included for analysis of cardiovascular risk associated with WCH in patients without baseline antihypertensive treatment (untreated), or under antihypertensive treatment (treated) or mixed population (including both untreated and treated patients), respectively. In untreated cohorts, WCH was associated with a 38 and 20% increased risk of CVD and total mortality compared with normotension, respectively. In the mixed population, WCH was associated with a 19 and 50% increased risk of CVD and total mortality. However, in the treated patients, neither the risk of CVD, nor total mortality was increased in WCH. Meta-regression analyses indicated that neither differences of clinic blood pressure, nor out-of-office blood pressure variables were correlated with risk of CVD in WCH. CONCLUSION: We concluded that WCH is associated with long-term risk of CVD and total mortality in patients without antihypertensive treatment. Close follow-up should be performed in WCH patients.

Abstract N 6 ‐methyladenosine (m 6 A) and long noncoding RNAs (lncRNAs) are both crucial regulators in non‐small‐cell lung cancer (NSCLC) tumorigenesis. However, the pathological roles of m 6 A and lncRNAs in NSCLC progression are still limited and undefined. Here, lncRNA ABHD11‐AS1 was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients. Functionally, ABHD11‐AS1 promoted the proliferation and Warburg effect of NSCLC. Mechanistically, m 6 A profile was analyzed by methylated RNA immunoprecipitation sequencing (MeRIP‐Seq). MeRIP‐Seq presented that there was m 6 A modification site in ABHD11‐AS1. m 6 A methyltransferase‐like 3 (METTL3) installed the m 6 A modification and enhanced ABHD11‐AS1 transcript stability to increase its expression. In conclusion, our findings highlight the function and mechanism of METTL3‐induced ABHD11‐AS1 in NSCLC and inspire the understanding of m 6 A and lncRNA in cancer biology.