Low-intensity extracorporeal shock wave therapy for Peyroniès disease: a systematic review and meta-analysis.

BACKGROUND: A systematic review of the evidence was conducted to assess the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) for patients with Peyronie`s Disease (PD). METHODS: A comprehensive search of the Cochrane Registry, PubMed and Embase databases was conducted to identify all controlled trials, including randomised controlled trials (RCTs), cohort studies and case-control studies, focusing on the efficacy of LI-ESWT in treating PD, and published before February 2023. The size of plaques, curvature deviation, visual analog scale [VAS] and International Index of Erectile Function (IIEF) were the most commonly used tool to evaluate the treatment effectiveness of LI-ESWT. RESULTS: There were 7 studies including  475 patients from 1999 to 2023. The meta-analysis of the data revealed that LI-ESWT could considerably enhance the proportion of men experiencing a reduction in penile plaques (RD 0.27, 95% CI: 0.04-0.50, P = 0.02), improvement in penile curvature (RD: 0.13; 95% CI, 0-0.26; p = 0.05), alleviation of pain (RD 0.22, 95% CI: 0.01-0.42, P = 0.04), and complete remission (RD 0.38, 95% CI 0.23-0.52, P < 0.00001). However, there were no significant differences in improvement of sexual function (MD: 1.44; 95% CI, -3.10-5.97; p = 0.53) between LI-ESWT and the placebo group. CONCLUSIONS: According to these studies, LI-ESWT has the potential to decrease plaque size and improve penile curvature or pain in men with PD. The publication of robust evidence from additional well-designed long-term multicenter randomized controlled trials would provide more confidence regarding use of these devices in patients with PD.

Inhibition of autophagy via 3-methyladenine alleviates the progression of preeclampsia.

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis reveals significant enrichment of genes related to autophagy-related signaling pathways, including the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the mTOR signaling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examine the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviates the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). The findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.

Lateral incision 1-stage urethroplasty with oral mucosal graft for patients with penile urethral stricture after hypospadias repair-a preliminary report.

PURPOSE: To report our early experience of a novel surgical approach for penile urethral strictures after hypospadias repair, using a lateral incision to keep the ventral tissue and vasculature of the penis intact and to avoid the need for tissue interposition. PATIENTS AND METHODS: A total of 21 patients underwent lateral incision 1-stage urethroplasty with oral mucosal graft. The median age of the patients was 21 years old (range, 13-47). The median number of prior procedures for hypospadias repair was 3 (range, 1-9) with 18 of 21 patients (85.7%) undergoing greater than 1 prior reconstructive procedure. The mean length of the penile urethral strictures was 4.5 ± 1.7 cm, with a range of 1.0 to 8.0 cm. Selection criteria for lateral incision 1-stage urethroplasty include: non-obliterative stricture, no or mild penile curvature and no urethrocutaneous fistula. RESULTS: Median follow-up was 30 months (range, 6-73). Success was achieved in 17 of 21 patients (80.9%). The 4 (19.0%) patients with treatment failure developed recurrent urethral strictures. Of the 4 men with recurrent strictures, 3 were ultimately treated successfully by DVIU (2) or two-stage urethroplasty (1), and one patient chose repeated dilation. CONCLUSIONS: For patients with penile urethral stricture after hypospadias repair with non-obliterative stricture, no significant penile curvature and no urethrocutaneous fistula, a lateral approach with oral mucosal graft is a simple technique that avoids the need for tissue interposition and keeps the penile ventral tissue and vasculature intact, resulting in a low risk of complications.

miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1.

Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial dysfunction induced by homocysteine are unknown. Here, we find that miR-205-5p alleviates pulmonary endothelial dysfunction by targeting FOXO1 in CBS +/‒ mice to protect against Hcy-induced pulmonary endothelial dysfunction. Mechanistically, we show that Hcy can lead to DNA hypermethylation of the miR-205-5p promoter due to the increased binding of DNMT1 to its promoter, which contributes to reduction of miR-205-5p expression. In summary, miR-205-5p promoter hypermethylation causes downregulation of miR-205-5p expression, resulting in a reduction in miR-205-5p binding to FOXO1 during homocysteine-induced pulmonary endothelial dysfunction. Our data indicate that miR-205-5p may be a potential therapeutic target against Hcy-induced pulmonary injury.

Cooperation between NSPc1 and DNA methylation represses HOXA11 expression and promotes apoptosis of trophoblast cells during preeclampsia.

Accumulating evidence has shown that the apoptosis of trophoblast cells plays an important role in the pathogenesis of preeclampsia, and an intricate interplay between DNA methylation and polycomb group (PcG) protein-mediated gene silencing has been highlighted recently. Here, we provide evidence that the expression of nervous system polycomb 1 (NSPc1), a BMI1 homologous polycomb protein, is significantly elevated in trophoblast cells during preeclampsia, which accelerates trophoblast cell apoptosis. Since NSPc1 acts predominantly as a transcriptional inactivator that specifically represses HOXA11 expression in trophoblast cells during preeclampsia, we further show that NSPc1 is required for DNMT3a recruitment and maintenance of the DNA methylation in the HOXA11 promoter in trophoblast cells during preeclampsia. In addition, we find that the interplay of DNMT3a and NSPc1 represses the expression of HOXA11 and promotes trophoblast cell apoptosis. Taken together, these results indicate that the cooperation between NSPc1 and DNMT3a reduces HOXA11 expression in preeclampsia pathophysiology, which provides novel therapeutic approaches for targeted inhibition of trophoblast cell apoptosis during preeclampsia pathogenesis.

Outcomes of early endoscopic realignment for blunt straddle injuries to the bulbar urethra: a single-center retrospective study.

BACKGROUND: The optimal acute management of patients with blunt straddle injury to the bulbar urethra remains in question. Conventionally, suprapubic diversion with delayed urethroplasty can always be considered, if necessary, but the role of early endoscopic realignment (EER) in the acute management of blunt straddle injuries to bulbar urethra is controversial. We report our clinical experience and outcomes with EER for patients with straddle injury to the bulbar urethra in a level one trauma center. METHODS: We retrospectively reviewed 44 male patients who were transferred to our trauma center between January 2013 and January 2019 for acute management of blunt straddle injury to the perineum leading to bulbar urethra injuries. We reviewed the medical records of those patients to identify demographics, emergency management and clinical outcomes. RESULTS: The most common injury mechanism was falling onto the perineum (n = 27, 61.4%), followed by motorcycle accident (n = 11, 25.0%) and bicycle accident (n = 6, 13.6%). Of the 44 patients, 14 (31.8%) were partial bulbar urethral ruptures and 30 (68.2%) were complete bulbar urethral ruptures. 31 (70.5%) patients successfully underwent EER and 13 (29.5%) patients failed attempted EER. the difference between successful EER attempts and failed ones in term of injured urethral mucosa integrity was statistically significant (P = 0.035, OR 8.667,95% CI: 0.998-75.235). In patients who underwent successful EER, urethral stricture occurred after catheter removal at a median of 8 (1-28) months in 24 (77.4%) patients and the mean stricture length was 1.8 ± 0.8 (0.5-3.0), which was not statistically significant when compared with those who failed EER (P = 0.103). Overall, 21 out of 24 (87.5%) patients with strictures after EER were successfully managed by urethroplasty. CONCLUSIONS: Although achieving a successful EER attempt is relatively easy for most patients with straddle injury to the bulbar urethra, it does not improve urethral healing significantly. Most patients with stricture formation after EER have to be cured with urethroplasty.

Oleic acid promotes cell invasion through an integrin-linked kinase signaling pathway in renal cell carcinoma.

The change of fatty acid composition has been regarded as an indicator of altered lipid metabolism during human tumourigenesis, but the details are still unclear. We have previously demonstrated a monounsaturated fatty acid (MUFA) named oleic acid (OA) was involved in renal cell carcinoma (RCC) cell growth, as an extracellular signaling molecule to regulate 786-O cell proliferation via the integrin-linked kinase (ILK) pathway. In this study, we further observe the effects of OA on cell invasion of RCC and the potential mechanism by which OA worked was determined. The transwell invasion assay showed OA increased cell invasion of RCC in a dose-dependent manner. Western blotting results indicated ILK, COX-2, and MMP-9 proteins were involved for their high expressions and these effects were reversed when down-regulating the expression of ILK by special siRNA. The MMPs inhibitor GM6001 could weaken the abilities of OA on RCC cells invasion. These results suggested MUFA indeed affected cell invasion of RCC, which was depended by the regulation of ILK pathway.

Aberrant MFN2 transcription facilitates homocysteine-induced VSMCs proliferation via the increased binding of c-Myc to DNMT1 in atherosclerosis.

It is well-established that homocysteine (Hcy) is an independent risk factor for atherosclerosis. Hcy can promote vascular smooth muscle cell (VSMC) proliferation, it plays a key role in neointimal formation and thus contribute to arteriosclerosis. However, the molecular mechanism on VSMCs proliferation underlying atherosclerosis is not well elucidated. Mitofusin-2 (MFN2) is an important transmembrane GTPase in the mitochondrial outer membrane and it can block cells in the G0/G1 stage of the cell cycle. To investigate the contribution of aberrant MFN2 transcription in Hcy-induced VSMCs proliferation and the underlying mechanisms. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase in atherosclerotic plaque of APOE-/- mice with hyperhomocystinaemia (HHcy) as well as in VSMCs exposed to Hcy in vitro. The DNA methylation level of MFN2 promoter was obviously increased in VSMCs treated with Hcy, leading to suppressed promoter activity and low expression of MFN2. In addition, we found that the expression of c-Myc was increased in atherosclerotic plaque and VSMCs treated with Hcy. Further study showed that c-Myc indirectly regulates MFN2 expression is duo to the binding of c-Myc to DNMT1 promoter up-regulates DNMT1 expression leading to DNA hypermethylation of MFN2 promoter, thereby inhibits MFN2 expression in VSMCs treated with Hcy. In conclusion, our study demonstrated that Hcy-induced hypermethylation of MFN2 promoter inhibits the transcription of MFN2, leading to VSMCs proliferation in plaque formation, and the increased binding of c-Myc to DNMT1 promoter is a new and relevant molecular mechanism.

SULT2B1b promotes epithelial-mesenchymal transition through activation of the ß-catenin/MMP7 pathway in hepatocytes.

Epithelial-mesenchymal transition (EMT) occurs in the progression of liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The hydroxysteroid sulfotransferase 2B1b (SULT2B1b) promotes the proliferation of hepatocarcinoma cells both in vitro and in vivo. However, the correlation between SULT2B1b and the EMT in hepatocytes has not yet been addressed. The present study demonstrated that the SULT2B1b overexpression promoted the EMT process in mouse primary hepatocytes in the absence or presence of TGF-ß1 treatment. Moreover, SULT2B1b interference suppressed the EMT and attenuated the migration and invasion abilities of human hepatocarcinoma BEL-7402 cells by inhibiting the activation of the ß-catenin/MMP-7 pathway. In summary, SULT2B1b enhanced the EMT of hepatocytes and promoted the migration and invasion abilities of BEL-7402 cells by activing the ß-catenin/MMP-7 pathway. Therefore, inhibition of SULT2B1b has therapeutic potential for the treatment of HCC.

Retraction Note: Association between serum vitamin D levels and the risk of kidney stone: evidence from a meta-analysis.

The Editors are retracting this article [1] because post-publication peer review has identified multiple errors in the methodology of this meta-analysis, which invalidate the conclusions drawn.

miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine.

MicroRNAs (miRNAs) are short non-coding RNA and play crucial roles in a wide array of biological processes, including cell proliferation, differentiation and apoptosis. Our previous studies found that homocysteine(Hcy) can stimulate the proliferation of vascular smooth muscle cells (VSMCs), however, the underlying mechanisms were not fully elucidated. Here, we found proliferation of VSMCs induced by Hcy was of correspondence to the miR-125b expression reduced both in vitro and in the ApoE knockout mice, the hypermethylation of p53, its decreased expression, and DNA (cytosine-5)-methyltransferase 3b (DNMT3b) up-regulated. And, we found DNMT3b is a target of miR-125b, which was verified by the Dual-Luciferase reporter assay and western blotting. Besides, the siRNA interference for DNMT3b significantly decreased the methylation level of p53, which unveiled the causative role of DNMT3b in p53 hypermethylation. miR-125b transfection further confirmed its regulative roles on p53 gene methylation status and the VSMCs proliferation. Our data suggested that a miR-125b-DNMT3b-p53 signal pathway may exist in the VSMCs proliferation induced by Hcy.

Association between serum vitamin D levels and the risk of kidney stone: evidence from a meta-analysis.

BACKGROUND: Many epidemiological studies have conducted to evaluate the association between serum vitamin D levels and the risk of kidney stone. The aim of this study was to summarize the evidence from epidemiological studies between them. METHODS: Pertinent studies were identified by a search of PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medical literature up to July 2015. Standardized mean difference (SMD) was conducted to combine the results. Random-effect model was used. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Seven articles involving 451 kidney stone cases and 482 controls were included in this meta-analysis. Our pooled results suggested that kidney stone patients had a significantly higher serum vitamin D level compared with controls [summary SMD = 0.65, 95 % CI = 0.51, 0.79, I(2) = 97.0 %]. The associations were also significant both in Europe [SMD = 0.35, 95 % CI = 0.17, 0.53] and in Asia [SMD = 1.00, 95 % CI = 0.76, 1.25]. No publication bias was found. CONCLUSIONS: Our analysis indicated that serum vitamin D level in kidney stone patients was significantly higher than that in non-kidney stone controls, both in Europe and Asia populations.

Association between X-ray repair cross-complementing group 1 Arg194Trp polymorphism and prostate cancer risk.

X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity. Previous studies on the association between XRCC1 Arg194Trp polymorphism and prostate cancer risk reported conflicting results. To get a more precise assessment of the association between XRCC1 Arg194Trp polymorphism and prostate cancer risk, we performed a meta-analysis of previously published studies. Eligible studies were searched in PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. Nine studies with a total of 5,407 subjects were finally included into the meta-analysis. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the association. Overall, there was no obvious association between XRCC1 Arg194Trp polymorphism and prostate cancer risk (Trp vs. Arg: OR = 1.02, 95%CI 0.84-1.25, P = 0.824; TrpTrp vs. ArgArg: OR = 1.17, 95%CI 0.83-1.66, P = 0.374; TrpTrp/ArgTrp vs. ArgArg: OR = 1.00, 95%CI 0.79-1.28, P = 0.990; TrpTrp vs. ArgArg/ArgTrp: OR = 1.20, 95%CI 0.85-1.68, P = 0.301). Subgroup analysis according to ethnicity also detected no significant association in both Asians and Caucasians. In conclusion, the meta-analysis suggests that there is no obvious association between XRCC1 Arg194Trp polymorphism and prostate cancer risk.

[Clinical characteristics of adrenal gland trauma].

OBJECTIVE: To explore the clinical characteristics of adrenal gland trauma. METHODS: A retrospective review was performed for 17 patients presenting with adrenal gland injury diagnosed by computed tomography (CT). There were 11 males and 6 females with an average age of 14-60 (38 ± 12) years. The injuries occurred as the consequence of motor vehicle crash (n = 13) and secondarily to a fall (n = 4). The average time from accident to admission was 5.0 ± 4.1 hours and the average injury severity score (ISS) 31.5 ± 10.3. Among 9 patients with throat injuries, there were pulmonary contusion, hematopneumothrax and rib fracture, followed by extremity fracture (n = 8) and pelvis fracture (n = 7). Additionally, 3 patients had injuries to vertebral column and 4 suffered closed cranial injury. There were 3 patients with liver injury, including subcapsular hematoma (n = 2) and laceration (n = 1). The urinary related injuries included renal contusion and laceration (n = 5) and urethral injury (n = 1). Among them, 15 had injuries to right adrenal glands and 2 to left ones. The CT findings of adrenal trauma were adrenal contusion and focal hematoma. All patients received conservative treatment. RESULTS: No patient died. The complications of urinary tract infection (n = 6) , deep vein thrombosis (n = 3), pneumonia (n = 3) and gastrointestinal ulceration (n = 2) improved with conservative treatment.Vital signs were all stable after 1 week treatment except for 1 patient operated for intracranial hematoma. The average follow-up period was 2.0- 12.0 (5.5 ± 2.7) weeks for 11 patients. The re-examination of CT showed a absorption of hematoma. And 2 cases had a complete absorption. CONCLUSIONS: Adrenal gland injury is rare and there is a right-sided preponderance.It is associated with high injury severity.For a lack of obvious clinical manifestations, missed diagnosis is frequently made. CT scan is the first-choice diagnostic tool for adrenal gland injury. Conservative treatment is often satisfactory and hormonal supplement unnecessary.

[Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms presenting for urologic care].

OBJECTIVE: To identify the risk factors in interstitial cystitis/painful bladder syndrome (IC/PBS) patients with lower urinary tract symptoms (LUTS) without urinary tract infection or benign prostate hyperplasia in China. METHODS: A total of 954 outpatients with LUTS presenting for care to urology clinics at 8 hospitals throughout China from November 20, 2008 to August 24, 2012 were surveyed with a standardized questionnaire and validated outcome measures. The definitions for IC/PBS based on the O'Leary-Sant interstitial cystitis symptom and problem indices were used. The possible risk factors was analyzed with the Fisher's exact and Pearson chi-square tests. And multivariate predictive models were developed with binary Logistic regression methods. RESULTS: There were 491 females and 463 males. And 44.7% (427/954) met the criteria for IC/PBS. There was significant gender difference (51.7% (254/491) vs 37.4% (173/463), P < 0.05) . After adjusting for confounding factors, bladder pain was significantly associated with stimulatory foods (OR: 81.16, 95%CI: 11.50-590.00, P = 0.001) and anorectal disease (OR: 54.90, 95%CI: 9.52-401.00, P = 0.001) in females. Caffeine beverage intake (OR: 4.29, 95%CI: 1.86-9.86, P = 0.001) was the only modifiable association according to multivariate analysis of males. CONCLUSIONS: Stimulatory foods, anorectal disease and caffeine beverages are potential risk factors for IC/PBS.Further studies are necessary to determine their roles in the pathogenesis of this disorder.

[Surgical treatment of bone metastases from renal cell carcinoma].

OBJECTIVE: To retrospectively analyze the survival of renal cell carcinoma patients with bone metastases, evaluate the effect of treatment and identify the prognostic factors in these patients. METHODS: A total of 66 renal cell carcinoma patients with bone metastases treated at our hospital between October 1990 and October 2010 were divided into 3 groups: solitary bone metastasis referred for radical surgery (n = 19); palliative surgery for solitary/multiple bone metastasis (n = 31); extraosseous metastasis without orthopedic surgery (n = 16). The effects of different variables on survival were determined according to the Kaplan-Meier method and Log-Rank test. And Cox proportional hazard regression model was used to estimate the prognostic factors. RESULTS: Their mean follow-up period was 25 (6-68) months. The survival significantly improved if bone metastases were solitary (45 vs 29 and 13 months, both P < 0.01), there was no vertebral bone involvement (31 vs 10 months, P < 0.01) and radical surgery was performed (50 vs 28 and 13 months, both P < 0.01). Age, gender, tumor size, alkaline phosphatase and lactate dehydrogenase had no effect on survival (all P > 0.05). Based on Cox regression analysis, survival was influenced by the number of metastasis foci (RR = 0.259, 95%CI:0.075-0.897) , type of procedure (RR = 17.845, 95%CI:4.246-74.992) and vertebral bone involvement (RR = 4.526, 95%CI:1.896-10.803) (all P < 0.05). CONCLUSIONS: Surgery is a better option for achieving local tumor control, providing good function and increasing the survival of patients with bone metastases. And radical resection is indicated for the patients with a solitary metastasis.

The prognostic value of preoperative plasma fibrinogen in Asian patients with urothelial cancer: a systematic review and meta-analysis.

Objective: We conducted this meta-analysis to comprehensively explore the prognostic value of the preoperative plasma fibrinogen in Asian patients diagnosed with urothelial cancer (UC). Methods: After a systematic search of Web of Science, PubMed, and Embase before May 2024, we included 10 studies in our meta-analysis. The hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression free survival (PFS) were estimated using fixed effect model. Results: This meta-analysis included a total of 2875 patients. UC patients with an elevated preoperative plasma fibrinogen had worse OS (pooled HR: 2.13, 95% CI: 1.81-2.51; P<0.001), CSS (pooled HR: 2.22, 95% CI: 1.83-2.70; P<0.001), RFS (pooled HR: 1.90, 95% CI: 1.59-2.27; P<0.001), and PFS (pooled HR: 2.12, 95% CI: 1.36-3.29, P=0.001). No significant heterogeneity or publication bias was found. Additionally, statistically significant pooled HRs were also calculated in subgroup analysis when stratified by cancer type, country, and cut-off value. Conclusions: The presence of elevated preoperative plasma fibrinogen levels is significantly correlated with unfavorable tumor outcomes in UCs.

Dielectric-Enhanced, High-Sensitivity, Wide-Bandwidth, and Moisture-Resistant Noncontact Triboelectric Sensor for Vibration Signal Acquisition.

Noncontact triboelectric sensors (TESs) have the potential to enhance self-powered sensing performance by eliminating the need for physical contact. This study demonstrates a strategy to construct noncontact TES that enables self-powered sensing and vibration signal acquisition with high sensitivity and wide bandwidth. The incorporation of carbon nanotubes into nitrocellulose (CNTs/NC) endows the tribopositive layer with larger inner micro/nanocapacitances, consequently augmenting the charge storage capacity. As a result, the contactless sensing performance of CNTs/NC-based TES (CNTs/NC-TES) was enhanced by 146%. Correspondingly, the related theory and working mechanism of noncontact sensing were demonstrated. Furthermore, the CNTs/NC-TES exhibits optimal distance response sensitivity of 57.10 V mm-1, a wide-bandwidth response from 0.1 to 4000 Hz, and relative humidity (RH) stability. This contactless CNTs/NC-TES has the potential for high sensitivity and wide frequency vibration monitoring in a high-RH environment.

Novel long noncoding lncARF mediated hyperhomocysteinemia-induced atherosclerosis via autophagy inhibition in foam cells.

INTRODUCTION: Homocysteine (Hcy) is well recognized to be an independent risk factor for atherosclerosis. Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis, while the underlying mechanisms of its involvement in Hcy induced-atherosclerosis remain largely unknown. OBJECTIVES: The primary aim of this study is to assess the role of lncARF (autophagy-related factor induced by Hcy) in Hcy induced-atherosclerosis and related mechanism. METHODS: RNA sequencing of foam cells treated with Hcy revealed a novel specific long noncoding RNA called lncARF. Locked nucleic acid gapmeRs-mediated lncARF knockdown was used to explore the role of lncARF both in vivo and in vitro. Mass spectrometry, RNA pull-down and RNA immunoprecipitation (RIP) assays were employed to uncover a mechanistic role of lncARF. Mass array assay and chromatin immunoprecipitation (ChIP) were used to detect the transcriptional activation of lncARF mediated by transcription factor. Clinically, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of lncARF in atherosclerotic patients with hyperhomocysteinemia (HHcy). RESULTS: We observed that the expression of lncARF was substantially upregulated in atherosclerotic plaques, and knockdown of lncARF decreased the formation of atherosclerotic lesions by promoting autophagy in foam cells. Mechanistically, lncARF physically binds to RRAGD and inhibits its ubiquitination, further activating the PI3K/Akt and MAPK signaling pathways. Moreover, in vitro experiments showed that transcription factor FosB inhibited the binding of DNMT1 at the lncARF promoter, leading to transcriptional activation through DNA hypomethylation. Clinically, lncARF expression was positively correlated with serum Hcy levels, and it could distinguish atherosclerotic patients with HHcy with a high area under the ROC curve, sensitivity and specificity. CONCLUSIONS: Our study highlights the mechanisms of lncARF in protecting against the development of atherosclerosis involving the epigenetic modifications and RRAGD/PI3K/Akt and RRAGD/MAPK signaling pathways, which may provide novel diagnostic biomarkers to improve atherosclerosis treatment.