Effect of liquid level monitor gas injection point size on information source amplitude-frequency characteristics.

In order to analyse the effect of the injection point size of the CBM (Coalbed Methane) well level monitor on the amplitude and frequency of pressure pulsations in the wellhead manifold, numerical simulations and experiments were carried out to investigate the effect of different injection point sizes on the amplitude and frequency of pressure pulsations downstream of the sudden expansion structure. Using compressed air as the fluid and the size of the injection point as the variable, the amplitude and frequency of pressure pulsations at different locations downstream of the sudden expansion structure were tested. The results show that the pressure pulsation amplitude is affected by the size of the injection point, and the larger the injection point is, the larger the pressure pulsation amplitude is; the size of the injection point has less influence on the pressure pulsation frequency downstream of the protruding and expanding structure, and the pressure pulsation frequency at 0.5 m and 1 m downstream of the protruding and expanding structure is in the vicinity of 76 Hz. Therefore, the echo signal processing should be filtered around this frequency to obtain accurate liquid level echo signals, so as to improve the accuracy of liquid level monitoring and realise the efficient development of coalbed methane wells.

Lupiwighteone as an Antitumor Agent Reverses Multidrug Resistance in K562/ADR Cells by Regulating Cellular Prion Protein-Oct4 Axis.

INTRODUCTION: One of the many reasons for cancer treatment failure and recurrence is acquired Multidrug Resistance (MDR). Overcoming cancer drug resistance has been the focus of researchers' studies. Cellular prion protein (PrPC) is a glycophosphatidylinositol-anchored cell-surface glycoprotein that has been implicated in tumor behavior, including proliferation, apoptosis, invasion, metastasis, and chemoresistance. >Method: Lupiwighteone (Lup), a natural isoflavone found in the root of Glycyrrhiza glabra, has anticancer activity against prostate cancer cells, neuroblastoma cells, and human breast cancer cells. However, its pharmacological effects and mechanisms in drug-resistant cancer cells have not been reported. In this study, we used an adriamycin- resistant leukemia K562 cell model, and for the first time, we investigated the reversal effect of Lup on its MDR and the potential mechanism. RESULT: The results indicated that Lup could induce apoptosis through the mitochondrial pathway while upregulating the expression of related apoptotic proteins, such as Bax, Cyto C, Caspase-3, and PARP1. Autophagy is commonly recognized as a protective mechanism that mediates MDR during treatment. We found that Lup induced cellular autophagy while upregulating the expression of related autophagy proteins such as Beclin 1 and LC3 II. CONCLUSION: In addition, when Lup was combined with adriamycin, Lup decreased the IC50 of K562/ADR cells; moreover, Lup can downregulate the expression of drug-resistant proteins, suggesting that Lup can reverse drug resistance. Further studies have shown that Lup can downregulate the expression of PrPC-PI3K-Akt axis proteins and PrPC-Oct4 axis proteins. This study demonstrated that Lup has the potential to inhibit the proliferation of K562/ADR cells by targeting PrPC, and further study of the signaling pathway associated with PrPC may provide the experimental basis for the treatment of drug-resistant leukemia.

Visual and refractive outcomes of opposite clear corneal incision combined with rotationally asymmetric multifocal intraocular lens implantation.

Purpose: To evaluate the visual and refractive outcomes of astigmatic cataract patients following opposite clear corneal incision (OCCI) combined with rotationally asymmetric multifocal intraocular lens (IOL) implantation. Setting: Department of Ophthalmology, Zhongshan Hospital (Xiamen), Fudan University, People's Republic of China. Design: Retrospective cohort study. Methods: This study comprised 58 cataract eyes of 54 patients with corneal astigmatism who underwent phacoemulsification and rotationally asymmetric multifocal IOL implantation which received either OCCI (OCCI group) or a single clear corneal incision (SCCI group). The follow-up period was 3 months after surgery. Distance, intermediate and near visual acuity, refractive outcomes, and corneal anterior keratometry were compared between the two groups. Vector analysis was used to evaluate astigmatism correction. Results: Three months after surgery, the distance, intermediate and near visual acuity, and sphere remained comparable between the two groups, but a significant difference was detected in residual astigmatism and anterior corneal keratometric astigmatism. In the OCCI group, the residual astigmatism and keratometric astigmatism were -0.60 ± 0.29 D and 0.59 ± 0.28 D, respectively, which were lower than those in SCCI groups (-1.18 ± 0.47 D and 1.15 ± 0.45 D, both p < 0.05). In vector analysis, the difference vector (DV), angle of error (AoE), absolute AoE, index of success (IoS) and correction index (CI) were statistically significantly different between the two groups (p < 0.05). Conclusion: OCCI combined with rotationally asymmetric multifocal intraocular lens implantation showed predictable and desirable efficacy in treating cataract patients with astigmatism.

Fibrinogen and tumors.

Elevated plasma fibrinogen (Fg) levels consistently correlate with an unfavorable prognosis in various tumor patient cohorts. Within the tumor microenvironment, aberrant deposition and expression of Fg have been consistently observed, interacting with multiple cellular receptors and thereby accentuating its role as a regulator of inflammatory processes. Specifically, Fg serves to stimulate and recruit immune cells and pro-inflammatory cytokines, thereby contributing to the promotion of tumor progression. Additionally, Fg and its fragments exhibit dichotomous effects on tumor angiogenesis. Notably, Fg also facilitates tumor migration through both platelet-dependent and platelet-independent mechanisms. Recent studies have illuminated several tumor-related signaling pathways influenced by Fg. This review provides a comprehensive summary of the intricate involvement of Fg in tumor biology, elucidating its multifaceted role and the underlying mechanisms.

5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

Purpose: Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. Methods: The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Results: Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. Conclusions: We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.

Research trends in chemogenetics for neuroscience in recent 14 years: A bibliometric study in CiteSpace.

BACKGROUND: Chemogenetics has been widely adopted in Neuroscience. Neuroscience has become a hot research topic for scientists. Therefore, the purpose of this study is to explore the current status and trends in the global application of chemogenetics in neuroscience over the last 14 years via CiteSpace. METHODS: Publications related to chemogenetics in neuroscience were retrieved from the Science Citation Index-Extended Web of Science from 2008 to 2021. We used CiteSpace to analyze publications, citations, cited journals, countries, institutions, authors, cited authors, cited references, and keywords. RESULTS: A total of 947 records were retrieved from 2008 to 2021 on February 21, 2022. The number and rate of publications and citations increased significantly. Journal of Neuroscience was the most cited journal, and BRAIN RES BULL ranked first in the centrality of cited journals. The United States of America (USA) had the highest number of publications among the countries. Takashi Minamoto was the most prolific author and Armbruster BN ranked the first among authors cited. The first article in the frequency ranking of the references cited was published by Roth BL. The keyword of "nucleus accumben (NAc)" had the highest frequency. The top 3 keywords with the strongest citation bursts include "transgenic mice," "cancer," and "blood-brain barrier." CONCLUSION: The period 2008 to 2021 has seen a marked increase in research on chemogenetics in neuroscience. The application of chemogenetics is indispensable for research in the field of neuroscience. This bibliometrics study provides the current situation and trend in chemogenetic methods in neuroscience in recent 14 years, which may help researchers to identify the hot topics and frontiers for future studies in this field.

ABPP-CoDEL: Activity-Based Proteome Profiling-Guided Discovery of Tyrosine-Targeting Covalent Inhibitors from DNA-Encoded Libraries.

DNA-encoded chemical library (DEL) has been extensively used for lead compound discovery for decades in academia and industry. Incorporating an electrophile warhead into DNA-encoded compounds recently permitted the discovery of covalent ligands that selectively react with a particular cysteine residue. However, noncysteine residues remain underexplored as modification sites of covalent DELs. Herein, we report the design and utility of tyrosine-targeting DELs of 67 million compounds. Proteome-wide reactivity analysis of tyrosine-reactive sulfonyl fluoride (SF) covalent probes suggested three enzymes (phosphoglycerate mutase 1, glutathione s-transferase 1, and dipeptidyl peptidase 3) as models of tyrosine-targetable proteins. Enrichment with SF-functionalized DELs led to the identification of a series of tyrosine-targeting covalent inhibitors of the model enzymes. In-depth mechanistic investigation revealed their novel modes of action and reactive ligand-accessible hotspots of the enzymes. Our strategy of combining activity-based proteome profiling and covalent DEL enrichment (ABPP-CoDEL), which generated selective covalent binders against a variety of target proteins, illustrates the potential use of this methodology in further covalent drug discovery.

Effect of perioperative acupoint electrical stimulation on macrophages in mice under operative stress.

The strong perioperative stress response caused by surgical anesthesia can significantly suppress immune function, and the body is in a state of immunosuppression for 3 to 4 days after surgery, which leads to an increase in the probability of postoperative infection. Traditional Chinese medicine believes that acupuncture points can "reconcile yin and yang", promote the recovery of immune function, and help reduce the incidence of postoperative infection. Macrophages are an important type of immune cells that participate in the body's innate immunity. They have powerful phagocytosis and clearance functions. They can be polarized into M1 and M2 types under the regulation of the body, and play different roles in fighting microbial infections. Among them, the M1 type can participate in the elimination of pathogens. In this study, we will investigate the perioperative acupoint electrical stimulation to alleviate the immunosuppressive state of surgical stress mice, clarify the regulation of perioperative acupoint electrical stimulation on glucocorticoids and the relationship between NF-κB molecules and macrophage polarization.The key molecules of related pathways were verified by glucocorticoid receptor inhibitors, and it was found that electrical stimulation of acupoints during the perioperative period can affect the polarization of macrophages in surgically stressed mice to the M1 type by reducing the level of glucocorticoids and promoting the expression of NF κB molecules. Further reveal the partial mechanism of electroacupuncture regulating the anti-inflammatory and pro-inflammatory processes of macrophages in the immune response.

Separation performance of hydrocyclone oil removal device influenced by oil droplet trajectory and oil drop characteristics.

Cyclone separation is an effective method for the treatment of oily wastewater from offshore oil production platforms. There is a lack of research on the impact of dispersion on the separation efficiency of current liquid-liquid separation hydrocyclones. A numerical simulation method was used to study the effect of the oil droplet characteristic parameters on the separation efficiency of a hydrocyclone oil removal device. An analysis of the trajectory of oil droplets revealed the oil removal mechanism of the hydrocyclone oil removal device: under the guidance of tangential velocity, the oil-water mixed fluid in the equipment generates different centrifugal forces due to the density difference, so oil and water adopt different flow paths to flow out. The effects of the particle diameter, velocity, and concentration of the inlet oil droplet on the separation efficiency were investigated. The droplet size had a positive effect on the separation efficiency, the oil concentration had a negative effect on the separation efficiency, and the speed of the oil drop was directly proportional to the separation efficiency within a certain range. These studies improved the basis for the efficient application of hydrocyclone oil removal devices.

Genome-wide identification of PLATZ genes related to cadmium tolerance in Populus trichocarpa and characterization of the role of PtPLATZ3 in phytoremediation of cadmium.

Plant AT-rich sequence and zinc-binding (PLATZ) proteins are a class of plant-specific zinc finger transcription factors that perform critical functions in plant development and resistance. However, the function of PLATZs in heavy metal tolerance has not yet been investigated. Moreover, only a few PLATZ proteins have been functionally characterized in tree species. In this study, we identified 18 PtPLATZ genes in Populus trichocarpa, an important woody model plant, and classified them into five groups. PtPLATZ genes attributed to the same clade usually possess similar exon-intron structures containing two or three introns, as well as a similar motif composition. Furthermore, chromosomal location analysis indicated an uneven distribution of PtPLATZ genes on 13 of the 19 Populus chromosomes. Promoter cis-acting element prediction and gene expression analysis showed that PtPLATZ genes were highly responsive to heavy metal stress. Heterologous yeast expression revealed that PtPLATZ1, PtPLATZ2, PtPLATZ3, PtPLATZ4, PtPLATZ8 and PtPLATZ9 are significantly involved in Cd tolerance. In addition, transgenic expression of PtPLATZ3 significantly enhanced Cd tolerance and accumulation, slowed the decline in chlorophyll content, maintained membrane integrity in Populus, and increased the expression of genes related to Cd tolerance and accumulation. In conclusion, our results suggest the potential of PtPLATZ3 to improve Cd tolerance and accumulation in Populus, which is of great significance for phytoremediation.

Perioperative transcutaneous electrical acupoint stimulation (pTEAS) in pain management in major spinal surgery patients.

BACKGROUND: Lumbar disc herniation is seen in 5-15% of patients with lumbar back pain and is the most common spine disorder demanding surgical correction. Spinal surgery is one of the most effective management for these patients. However, current surgical techniques still present complications such as chronic pain in 10-40% of all patients who underwent lumbar surgery, which has a significant impact on patients' quality of life. Research studies have shown that transcutaneous electrical acupoint stimulation (TEAS) may reduce the cumulative dosage of intraoperative anesthetics as well as postoperative pain medications in these patients. OBJECTIVE: To investigate the effect of pTEAS on pain management and clinical outcome in major spinal surgery patients. METHODS: We conducted a prospective, randomized, double-blind study to verify the effect of pTEAS in improving pain management and clinical outcome after major spinal surgery. Patients (n = 90) who underwent posterior lumbar fusion surgery were randomized into two groups: pTEAS, (n = 45) and Control (n = 45). The pTEAS group received stimulation on acupoints Zusanli (ST.36), Sanyinjiao (SP.6), Taichong (LR.3), and Neiguan (PC.6). The Control group received the same electrode placement but with no electrical output. Postoperative pain scores, intraoperative outcome, perioperative hemodynamics, postoperative nausea and vomiting (PONV), and dizziness were recorded. RESULTS: Intraoperative outcomes of pTEAS group compared with Control: consumption of remifentanil was significantly lower (P < 0.05); heart rate was significantly lower at the end of the operation and after tracheal extubation (P < 0.05); and there was lesser blood loss (P < 0.05). Postoperative outcomes: lower pain visual analogue scale (VAS) score during the first two days after surgery (P < 0.05); and a significantly lower rate of PONV (on postoperative Day-5) and dizziness (on postoperative Day-1 and Day-5) (P < 0.05). CONCLUSION: pTEAS could manage pain effectively and improve clinical outcomes. It could be used as a complementary technique for short-term pain management, especially in patients undergoing major surgeries. TRIAL REGISTRATION: ChiCTR1800014634, retrospectively registered on 25/01/2018. http://medresman.org/uc/projectsh/projectedit.aspx?proj=183.

Orally Bioavailable Enzymatic Inhibitor of CD38, MK-0159, Protects against Ischemia/Reperfusion Injury in the Murine Heart.

CD38 is one of the major nicotinamide adenine dinucleotide (NAD+)- and nicotinamide adenine dinucleotide phosphate (NADP+)-consuming enzymes in mammals. NAD+, NADP+, and their reduced counterparts are essential coenzymes for numerous enzymatic reactions, including the maintenance of cellular and mitochondrial redox balance. CD38 expression is upregulated in age-associated inflammation as well as numerous metabolic diseases, resulting in cellular and mitochondrial dysfunction. Recent literature studies demonstrate that CD38 is activated upon ischemia/reperfusion (I/R), leading to a depletion of NADP+, which results in endothelial damage and myocardial infarction in the heart. Despite increasing evidence of CD38 involvement in various disease states, relatively few CD38 enzymatic inhibitors have been reported to date. Herein, we describe a CD38 enzymatic inhibitor (MK-0159, IC50 = 3 nM against murine CD38) that inhibits CD38 in in vitro assay. Mice treated with MK-0159 show strong protection from myocardial damage upon cardiac I/R injury compared to those treated with NAD+ precursors (nicotinamide riboside) or the known CD38 inhibitor, 78c.

The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.

We here examined the potential biological function of phosphoenolpyruvate carboxykinase 1 (PCK1) in angiogenesis. shRNA- or CRISPR-Cas9-induced PCK1 depletion potently inhibited endothelial cell proliferation, migration, sprouting, and tube formation, whereas ectopic PCK1 overexpression exerted opposite activity. In HUVECs, Gαi3 expression and Akt activation were decreased following PCK1 depletion, but were augmented by ectopic PCK1 overexpression. In vivo, retinal expression of PCK1 gradually increased from postnatal day 1 (P1) to P5. The intravitreous injection of endothelial-specific PCK1 shRNA adenovirus at P1 potently inhibited the radial extension of vascular plexus at P5. Conditional endothelial knockdown of PCK1 in adult mouse retina increased vascular leakage and the number of acellular capillaries while decreasing the number of RGCs in murine retinas. In diabetic retinopathy patients, PCK1 mRNA and protein levels were up-regulated in retinal tissues. Together, PCK1 is essential for angiogenesis possibly by mediating Gαi3 expression and Akt activation.

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species.

BACKGROUND/AIMS: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm2), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. METHODS: We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. RESULTS: Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-ß-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. CONCLUSIONS: Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study.

A New Anti-Inflammatory Alkaloid from Roots of Heracleum dissectum.

Using various chromatographic methods, a new piperidinone alkaloid, (3S)-3-{4-[(1E)-3-hydroxyprop-1-en-1-yl]-2-methoxyphenoxy}piperidin-2-one (1), together with 10 known compounds, bergapten (2), xanthotoxol (3), isopimpinellin (4), isobergapten (5), heratomol-6-O-ß-d-glucopyranoside (6), scopoletin (7), apterin (8), 3-methoxy-4-ß-d-glucopyranosyloxypropiophenone, (praeroside; 9), tachioside (10) and coniferin (11), were isolated from roots of Heracleum dissectum Ledeb. Their structures were elucidated on the basis of physicochemical properties and the detailed interpretation of various spectroscopic data. All the isolated compounds were screened for anti-inflammatory activity in vitro. As the results, compound 1 and 8 showed significantly inhibitory activity on nitric oxide production in RAW264.7 cells.

Burden of basal cell carcinoma in USA.

Basal cell carcinoma (BCC) is the most common malignancy diagnosed in the USA and its incidence continues to increase. While BCC is still most prevalent in the older segments of the population, it is becoming ever more frequent in younger individuals. The costs of treatment and morbidity associated with BCCs place a heavy public health and economic burden on patients, their families and the American healthcare system and underscore the importance of efficient management and prevention efforts directed toward this malignancy. In this article, we address economic aspects of BCC using evidence from large-scale epidemiological studies. This information may help clinicians in developing better and more cost-effective methods for dealing with the most common cancer in America and in the world.

Traditional versus streamlined management of basal cell carcinoma (BCC): A cost analysis.

BACKGROUND: Facing rising incidence of basal cell carcinoma (BCC) and increasing pressure to contain health care spending, physicians need to contemplate cost-effective paradigms for managing BCC. OBJECTIVE: We sought to perform a cost analysis comparing the traditional BCC management scheme with a simplified detect-and-treat scheme that eliminates the biopsy before initiating definitive treatment. METHODS: A decision analytic model was developed to compare the costs of traditional BCC management with the detect-and-treat scheme, under which qualifying lesions diagnosed clinically were either treated with shave removal or referred to Mohs micrographic surgery for on-site histologic check. Values for model parameters were based on literature and our institutional data analysis. Costs were based on 2014 Medicare fee schedule. RESULTS: The average cost per lesion with detect-and-treat scheme was $449 for non-Mohs micrographic surgery-indicated lesions (vs $566 with traditional management, $117 in savings) and $819 for Mohs micrographic surgery-indicated lesions (vs $864 with traditional management, $45 in savings). The combined weighted average savings per case was $95 (15% of total average cost). Conclusions were similar under various plausible scenarios. LIMITATIONS: Model parameter values may vary based on individual practices. CONCLUSIONS: A simplified management strategy eliminating routine pretreatment biopsy can reduce BCC treatment cost without compromising quality of care.

Growth-Curve Modeling of Nevi With a Peripheral Globular Pattern.

IMPORTANCE: Although nevi with a peripheral rim of globules (peripheral globular nevi [PGN]) observed with dermoscopy are associated with enlarging melanocytic nevi, their actual growth dynamics remain unknown. Because change is a sensitive but nonspecific marker for melanoma, beginning to understand the growth patterns of nevi may improve the ability of physicians to differentiate normal from abnormal growth and reduce unnecessary biopsies. OBJECTIVE: To study the growth dynamics and morphologic evolution of PGN on dermoscopy. DESIGN, SETTING, AND PARTICIPANTS: A total of 84 participants with 121 PGN from September 1, 1999, through May 1, 2013, were identified retrospectively. Cohorts were recruited from the Memorial Sloan Kettering Cancer Center; Melanoma Unit of the Hospital Clinic, University of Barcelona; and Study of Nevi in Children. All 3 cohorts underwent longitudinal monitoring with serial dermoscopic imaging of their PGN. Data analysis was performed from May 1, 2014, through April 1, 2015. MAIN OUTCOMES AND MEASURES: Establishment of the natural growth curve of PGN. The secondary aim was to establish the median time to growth cessation in those PGN for which the size eventually stabilized and/or had begun to decrease during the study period. RESULTS: The median duration of follow-up was 25.1 (range, 2.0-114.4) months. Most of the nevi (116 [95.9%]) enlarged at some point during sequential monitoring. The rate of increase in the surface area of PGN varied among cohorts and ranged from -0.47 to 2.26 mm2/mo (mean rate, 0.25 [95% CI, 0.14-0.36] mm2/mo). The median time to growth cessation in the 26 PGN that stabilized or decreased in size (21.5%) was 58.6 months. All lesions changed in a symmetric manner and 91 (75.2%) displayed a decrease in the density of peripheral globules over time. CONCLUSIONS AND RELEVANCE: Nevi displaying a peripheral globular pattern enlarged symmetrically with apparent growth cessation occurring during a span of 4 to 5 years. Our results reiterate the important concept that not all growth is associated with malignancy.