BackgroundAlzheimer's disease (AD) is characterized by amyloid-β plaques and tau aggregates, with autophagy dysfunction playing a key pathogenic role. While autophagy modulation shows therapeutic promise, comprehensive bibliometric analyses are lacking.ObjectiveThis study aims to map the research landscape of autophagy in AD through bibliometric analysis, identifying key trends, contributors, and emerging focus areas.MethodsWe analyzed 4018 publications (2003-2023) from Web of Science using VOSviewer and CiteSpace. Publication trends, influential authors, countries, institutions, and research hotspots were examined through co-occurrence, burst detection, and clustering analyses.ResultsAnnual publications have steadily increased, peaking in 2022. The US led in output and citations, with major contributions from the University of California and New York University. Ralph A. Nixon emerged as the most influential author. Early research (2003-2013) primarily focused on protein degradation mechanisms, whereas recent studies (2014-2023) emphasize mitochondrial dysfunction, apoptosis, and related pathways. Key evolving topics include endoplasmic reticulum stress and chaperone-mediated autophagy, with significant implications for therapeutic innovation.ConclusionsAutophagy plays a critical role in AD pathogenesis and represents a promising therapeutic target. Despite mechanistic advances, clinical translation remains challenging. Future research should prioritize multi-omics integration, drug delivery optimization, and managing risks associated with excessive autophagy activation. These findings provide valuable insights for developing novel AD therapies targeting autophagy.

Telomeres play a crucial role in the development and progression of cancers. However, the impact of telomere-related genes (TRGs) on the prognosis and tumor immune microenvironment (TIME) of gastric cancer (GC) remains unclear. Therefore, a comprehensive investigation of the association between TRGs and GC is necessary. The TRG risk panel was constructed by combining differentially expressed gene analysis, weighted gene co-expression network analyses, the Least Absolute Shrinkage and Selection Operator regression, and stepwise regression analysis in the TCGA cohort and has been validated in a GEO cohort. The major impacts of the signature on the TIME and immunotherapy response were also evaluated. The prognosis model comprised 9 TRGs (CABP2, CALML6, CFAP58, DST, ELOVL2, HIST1H3G, MYF6, PDE1B and TOP3B), stratifying patients into two risk groups. Individuals with low-risk scores exhibited superior prognoses than those with high-risk scores (P < 0.001). The prognostic signature was found to be an independent factor with good predictive power for overall survival. The high-risk group tended to have higher TME scores and an inert immune status with a higher infiltration proportion of Treg cells, M2 macrophages, resting dendritic cells and resting NK cells. Additionally, the low-risk group had higher TMB, lower TIDE and a higher immunotherapy response rate. Additionally, we confirmed the expression of the nine genes in GC tissues using RT-qPCR. Our TRG-based panel has a significant role in the prognosis, TIME, and immunotherapy response. This may suggest that the TRG panel could be a powerful tool for guiding clinical treatment decisions.

目的 探讨 Cleaner血栓清除系统联合导管接触性溶栓(catheter directed thrombolysis,CDT)治疗急性下肢深静脉血栓形成(deep venous thrombosis,DVT)的近期疗效.方法 回顾性分析2021 年 6 月至 2021 年 12 月空军军医大学西京医院收治的 48 例急性下肢DVT患者的临床资料,其中24 例行Cleaner血栓清除系统联合CDT治疗,24 例行单纯CDT治疗.比较两组患者治疗期间尿激酶总量、溶栓时间、住院时间、术后静脉通畅率及并发症发生情况.结果 两组患者手术均获成功.联合治疗组手术时间、术中出血量高于单纯CDT组,溶栓时间、住院时间、溶栓药物剂量明显低于单纯CDT组,血栓清除率、术后 24h大腿及小腿消肿率高于单纯CDT组,差异均有统计学意义(P＜0.05).术后随访6 个月,两组患者血栓形成后综合征发生率的比较差异无统计学意义(P＞0.05).结论 Cleaner血栓清除系统联合CDT治疗急性下肢DVT近期疗效显著,有助于减少溶栓时间、住院时间、尿激酶用量,降低出血风险.

目的 探讨不同减容方式治疗急性下肢深静脉血栓形成(DVT)的有效性及安全性.方法 收集2017年1月至2020年10月空军军医大学西京医院收治的136例急性下肢DVT患者的临床资料.根据治疗方式不同分将其为3组:A组46例,采用导管接触性溶栓(CDT)治疗;B组42例,在A组基础上采用AngioJet经皮机械血栓清除术(PMT)治疗;C组48例,在A组基础上采用Straub Aspirex PMT治疗.比较3组患者手术时间、术中出血量、溶栓时间、尿激酶用量、住院时间等围手术期指标,血栓清除率及术后24 h后患肢消肿程度,分析3组患者住院期间的不良反应发生情况,术后随访6、12个月PTS发生率.结果 A组患者手术时间均短于B、C组患者,术中出血量均低于B、C组患者,但溶栓时间、住院时间均长于B、C组患者,尿激酶用量明显多于B、C组患者,差异均有统计学意义(P<0.05).C组患者的手术时间短于B组患者,术中出血量低于B组患者,差异均有统计学意义(P<0.05);B、C组患者溶栓时间、住院时间、尿激酶用量比较,差异均无统计学意义(P>0.05).A组患者Ⅲ级血栓清除率、术后24 h大腿及小腿周径差小于B、C组患者,差异均有统计学意义(P<0.05);B、C组患者Ⅲ级血栓清除率、24 h大腿及小腿周径差比较,差异均无统计学意义(P>0.05).术后随访6、12个月,3组患者血栓后综合征(PTS)发生率比较,差异均无统计学意义(P>0.05).结论 AngioJet PMT及Straub Aspirex PMT联合CDT治疗急性下肢DVT均有较高的血栓清除率,可减少溶栓药物用量,缩短住院时间,安全性良好,可作为急性下肢DVT的常用方法.

目的 探讨髂股动脉损伤的手术方式与临床疗效.方法 收集2008年8月至2020年8月空军军医大学第一附属医院收治的95例髂股动脉损伤患者的临床资料.根据术前合并症、动脉损伤情况、伤口污染程度及远端肢体血供情况采取不同的手术方式.观察所有患者的手术情况并进行分组.比较采取不同手术方式治疗患者的临床特征.根据患者术前基线情况、术后复查结果,随访下肢血管彩色多普勒超声及踝肱指数(ABI),评估下肢动脉远端血运情况、支架通畅情况及术后患肢功能恢复情况.采用视觉模拟评分量表(VAS)对患者术前、术后及末次随访时的疼痛情况进行评价.结果 95例髂股动脉损伤患者中,共77例患者进行手术治疗,包括开放手术55例(开放手术组)和腔内手术22例(腔内手术组).截肢患者12例,截肢率为12.6％(12/95).两组患者的年龄、性别、术前心脑血管并发症发生率、术前有无合并感染、平均住院时间比较,差异均无统计学意义(P>0.05);开放手术组患者术前失血性休克、骨折的患者比例均高于腔内手术组患者,手术时间、ICU住院时间长于腔内手术组患者,术中出血量多于腔内手术组患者,差异均有统计学意义(P<0.05).腔内手术组患者末次随访时与本组术后的VAS评分比较,差异无统计学意义(P>0.05).两组患者末次随访时与本组术后的ABI比较,差异均无统计学意义(P>0.05).结论 外科手术是髂股动脉损伤的主要治疗方法,尤其适用于合并骨折、失血性休克及伤口污染的患者.与开放手术相比,腔内手术治疗髂股动脉损伤安全有效,具有创伤小、手术时间短、术后恢复快等优点,在充分掌握手术适应证的前提下可以作为首选.

目的 比较CleanerTM旋转式血栓清除系统、AngioJet血栓清除系统及Straub血栓清除系统在下肢深静脉血栓形成(LEDVT)中的应用效果及安全性.方法 在医院病例管理系统中选取2019年6月至2021年11月中国人民解放军空军军医大学西京医院甲乳血管外科收治的LEDVT患者64例,其中经CleanerTM旋转式血栓清除系统治疗者14例(A组)、经AngioJet血栓清除系统治疗者30例(B组)、经Straub血栓清除系统治疗者20例(C组).比较三组患者临床资料、术后即刻血栓清除效果、并发症发生率及血栓复发率;LEDVT患者术后即刻血栓清除效果影响因素分析采用多因素Logistic回归分析.结果 三组患者有肿瘤史者占比、有外科手术史者占比及术前血浆纤维蛋白原比较,差异有统计学意义(P<0.05).三组患者术后即刻血栓清除效果、并发症发生率及血栓复发率比较,差异无统计学意义(P>0.05).多因素Logistic回归分析结果显示,腔内血栓清除术类型并不是LEDVT患者术后即刻血栓清除效果的独立影响因素〔OR=1.333,95％CI(0.124,14.309),P>0.05〕.结论 CleanerTM旋转式血栓清除系统在LEDVT中的应用效果不劣于AngioJet血栓清除系统和Straub血栓清除系统,且安全性较高.

目的 探讨不同类型肺栓塞发病原因的临床分析,为肺栓塞防治提供理论依据.方法 收集2017年1月至2020年6月于空军军医大学第一附属医院的461例肺栓塞患者临床资料,分析不同类型肺栓塞的发病原因.结果 461例肺栓塞患者中,71.6％静脉系统血栓导致;5.4％由心源性导致;21.0％不明原因导致;0.9％因咯血行介入栓塞手术导致;1.1％肺癌导致;49.7％大面积肺栓塞(MPE),4.4％中央型深静脉血栓形成(DVT)导致,28.4％混合型DVT导致,45.0％周围型DVT导致;50.3％非大面积肺栓塞(NMPE),2.2％中央型DVT导致,12.1％混合型DVT导致,44.4％周围型DVT导致.不同肺栓塞类型中孤立性小腿肌间静脉血栓发生情况比较,差异无统计学意义(P>0.05).461例患者中,最终随访239例患者,平均随访时间(24.7±7.9)个月,痊愈88例,未痊愈151例.结论 肺栓塞发病原因较多,下肢DVT是肺栓塞发病的主要原因,其中孤立性小腿肌间静脉血栓也不可忽视,针对不同发病原因给予早期治疗可较好预防肺栓塞发生.

目的 评价Acotec药物涂层球囊(DCB)治疗下肢慢性缺血性疾病的有效性和安全性.方法 回顾性分析2016年4月至2020年1月期间收治的427例经DCB治疗的下肢慢性缺血性疾病患者,平均年龄为(67.3±9.97)岁,其中男329例,女98例,共481条下肢有528处闭塞性和(或)狭窄性病变.分为两组,股腘动脉组(n=351)与膝下动作组(n=76).每隔6个月对患者进行一次随访,主要评价终点包括晚期管腔丢失(LLL)、靶病变再狭窄、靶病变血运重建(TLR)和严重临床事件.结果 技术成功率为97.5％.DCB血管成形术后,59例(13.8％)因血流受限夹层或残余狭窄大于50％而植入支架.中位随访时间为27个月.术后1、2、3年的平均LLL分别为(1.00±0.30)、(1.73±0.41)、(2.14±0.40)mm.术后1年再狭窄率17.1％vs.24.1％(P=0.151),18.4％vs.29.8％(P=0.070)和26.7％vs.36.7％(P=0.277).血运重建率分别为8.0％vs.16.5％(P=0.032),9.9％vs.19.3％(P=0.065)和15.9％vs.23.3％(P=0.303).结论 Acotec DCB治疗下肢慢性缺血性疾病安全有效,股腘动脉的临床结局优于膝下动脉.

血栓闭塞性脉管炎是一种慢性炎性动脉闭塞性病变, 1908年,Buerger首次详细描述了该疾病的组织病理表现,又称为Buerger 's病[1].血栓闭塞性脉管炎主要累及中小动静脉,病情严重者可出现静息痛、肢体远端溃疡,甚至坏疽,严重影响患者的生活质量.

Background: At present, there are many clinical trials of drug coated balloon in the treatment of lower extremity arterial occlusive diseases, but there are not many clinical data in the real world study. Here we aimed to evaluate the efficacy and safety ofAcotec drug-coated balloon (DCB) for chronic ischemic disease in lower extremity. Methods: Clinical data of 435 patientswith 564occlusive/stenotic lesions in 492lower extremities treated by DCB from April 2016 toApril2019 were retrospectively analyzed.The mean age was 63years.Rutherford stage 2, 3, 4, 5, and 6 were classified in 11, 167, 182, 109, and 23 limbs, respectively.The mean length of the targeted lesions was 179.6mm. Of all the lesions, 436 located at femoraland/or popliteal arteries, and 128 at infra-popliteal arteries. All the patients were followed up at 6-month intervals. The major evaluation endpoints included late lumen loss (LLL), target lesion restenosis, target lesion revascularization (TLR), and severe clinical events including mortality and major amputation. Results: The technique success rate was 96.1%.Stents were placed in 57 (13.1%) cases for flow-limited dissections or remnant stenosisgreater than 50% after DCB angioplasty.The mean follow-up time was 28.5 ± 12.1 months (12-48 months). The meanLLLwas 1.1 mm, 1.8mm, and 2.8 mm, respectively, 1, 2, and 3 years after operation. The rate ofrestenosis and TLRwas 17.3%and8.2%, respectively, 1 year after operation; 20.6% and 11.6%, respectively, 2 years after operation; 29.4% and 18.3%, respectively, 3 years after operation.Fourteenpatientsdiedand 25received amputation. Conclusion: AcotecDCBwas safe and effective in treating chronic ischemic diseases of lower extremities.A better clinical outcome was achieved in femoro-popliteal arteries, compared toinfrapopliteal arteries.

目的:检测miR-34c-3p与M2型肿瘤相关巨噬细胞(tumor-associated macrophage,TAM)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达,并探讨其在乳腺癌发病中的意义.方法:选择2017年2月至2018年1月于西京医院就诊的68例TNBC患者作为实验组(A组),以同期就诊的70例乳腺纤维腺瘤患者作为对照组(B组).采用Real-time RT-PCR检测组织标本中miR-34c-3p的表达;流式细胞检测M2型TAM的表达;ELISA法检测血清中IL-10的表达.并进一步分析miR-34c-3p的表达与乳腺癌M2型TAM及血清IL-10水平的相关性.结果:A、B组miR-34c-3p的相对表达量分别为0.84±0.08、1.29±0.71,A组明显低于B组,差异有统计学意义(P＜0.05).与B组比较,A组M2型TAM(CD68+ CD163+)细胞比例显著升高(P＜0.05).A组血清IL-10的表达[(19.69±4.93) pg/ml]较B组[(17.26±3.51) pg/ml]显著升高,差异有统计学意义(P＜0.05).TNBC组织中miR-34c-3p的表达与M2型TAM比例及血清IL-10表达均呈显著负相关(r=-0.508,r=-0.656,P＜O.05).结论:TN BC组织中miR-34c-3p的表达下调,M2型TAM比例及血清IL-10表达均显著升高,促进TNBC进展.

目的 探讨INCRAFT覆膜支架系统腔内治疗腹主动脉瘤的安全性和有效性.方法 回顾性分析2017年11月至2019年2月空军军医大学西京医院 53 例利用腔内修复术治疗的腹主动脉瘤患者资料,其中使用INCRAFT覆膜支架系统26例,使用其他类型覆膜支架27例.对两组患者的一般资料、围术期治疗结果 及术后随访结果 进行比较.结果 手术成功率100％,INCRAFT覆膜支架组瘤颈平均角度为(44.15±18.79)°,平均长度为(22.42±10.43)cm,其他类型覆膜支架组瘤颈平均角度为(27.89±11.29)°,平均长度为(34.74±12.64)cm(P＜0.001).INCRAFT覆膜支架组的手术时间和住院花费高于其他类型覆膜支架组,差异有统计学意义,两组在失血量、围术期并发症、住院时间等差异无统计学意义.随访3～18个月,两组患者无死亡病例,在并发症及手术再干预率方面差异无统计学意义.结论 对于短瘤颈、瘤颈成角较大的腹主动脉瘤,可以应用INCRAFT覆膜支架系统腔内修复治疗,近期随访显示良好的有效性和安全性.

Objective To detect the expression of Survivin and Caspase-9 gene in Uygur breast cancer pa-tients with different HER-2 phenotypes,to find out the difference and association of the two genes and to find out the potential roles of the two genes breast cancer pathogenesis. Methods We selected 72 Uygur patients diag-nosed as breast cancer initially and they were divided into group A with HER-2 positive(n = 39)and group B with HER-2 negative(n = 33). Another 40 Uygur patients with benign breast were involved as the controls. Immunohis-tochemistry and real-time RT-PCR were used to detect the two genes,and analyze the differences and association of each gene between the groups. Results (1)The expression of Survivin gene in group A and B were higher than that in the control group. Further analysis showed that the expression of Survivin gene was enhanced in group A when compared with that in group B(P < 0.05);while even the expression of Survivin gene in group B was higher than that in the control group but no statistical difference was found(P > 0.05).(2)The expression of Caspase-9 gene in group A and B were lower than that in the control group. Real-time RT-PCR showed that the expression of Caspase-9 gene of group A was decreased when compared with that in group B(P < 0.05);While the expression of Caspase-9 gene of group B was slightly lower that of the control group but it showed no statistical significance (P > 0.05). Immunohistochemical results showed there were no statistical differences of expression of Caspase- 9 gene in group A and B and control group(all P > 0.05). The expression of Survivin and Caspase-9 gene was nega-tively associated in group A and B(P < 0.01;P < 0.05). Conclusions In Uygur patients with HER-2 positive breast cancer,the expression of Survivin gene is enhanced but that of caspase-9 gene is decreased,and they are negatively associated. Through inhabiting caspase-9 gene,Survivin gene may potentially lead to the occurrence of HER-2 positive breast cancer.

The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147 + cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147 + cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147 + BCSCs was enhanced compared with that in differentiated adherent progeny of CD147 + BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147 + BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147 + BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147 + BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell–like features in CD147 + BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs’ state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.

To further assess the efficacy and safety of recombinant human endostatin (rh‐endostatin), a Phase III, multicenter, prospective, randomized, controlled clinical trial was conducted. Patients to be treated with neoadjuvant docetaxel and epirubicin (DE) or DE plus rh‐endostatin (DEE) were eligible for this trial. The primary endpoint was clinical/pathological response. Secondary endpoints included adverse events and quality of life (QOL). Finally, 803 patients were enrolled and randomly assigned to receive DE (n = 402) or DEE (n = 401) regimen. After three cycles of neoadjuvant therapy, “complete response” achieved in 14.2% of patients in DEE group versus 6.7% in DE group, “partial response” achieved in 76.8% versus 71.1%, while “stable disease” in 6.0% versus 18.9%, “progressive disease” in 3.0% versus 3.2% of patients. The rate of objective response in DEE and DE group was 91.0% and 77.9%, respectively (p < 0.001). In spite of a relatively higher pathological complete response achieved following the combination therapy, no significant difference was found between two arms. Adverse events were mostly of Grades 1–2. No significant difference in adverse event and QOL was found between the two arms. In conclusion, the combination of chemotherapy and rh‐endostatin achieved better outcomes than chemotherapy alone, and thus can be considered as a promising therapeutic strategy for breast cancer.

随着人民生活水平不断提高和饮食结构的改变,下肢动脉缺血性疾病的发病率逐年升高,已成为威胁人类健康的主要疾病之一. 下肢动脉缺血性疾病的治疗分为传统外科手术和腔内治疗,近年来腔内治疗在保持其创伤小、术后恢复快等优点的同时,技术及器械也不断完善. 腔内治疗下肢动脉缺血性疾病已经成为主流,但腔内治疗后再狭窄是其发展的瓶颈. 近几年随着药物涂层球囊 (drug-coated balloon,DCB)的基础研究及临床应用,为下肢动脉缺血病变的治疗带来希望和曙光.

RATIONALE:Luminal subtype breast cancer, accounting for 70 to 80% of all breast cancers, has been reported to be associated with good prognosis. However, for the patients with large mass or worse mass position, omental flap transplantation may provide a new option for breast reconstruction.PATIENT CONCERNS:Ten patients (6 luminal B1, 2 luminal B2, 2 luminal A), were enrolled into the study, between January 23, 2015 and August 22, 2016. The mean age was 34.6 ± 6.96 (24-44) years old. Immunohistochemistry demonstrated that the tumor cells were positive for estrogen receptor and progestrone receptor.DIAGNOSES:According to the clinicopathological features, diagnosis of breast cancer patients were made.INTERVENTIONS:Breast-conserving surgery, laparoscopic greater omentum harvest and vascular anas-tomosis were carried out orderly. Postoperative operative results, cosmetic outcomes, complications, as well as blood supply were investigated for surgery evaluation. Reasonable chemotherapy and irradia-tion were adopted to patients according to the pathological condition.OUTCOMES:We successfully accomplished breast reconstruction by omental flap transplantation, ex-cept one failed case because of the necrosis of omentum and changed to fat transplantation. The volumes and symmetry of breasts were all satisfied. The blood supply was detected to be fluent. Only one case of slight hematoma and another case of one distant metastasis were observed during fol-low-up period. No arm mordities or arm movement restriction occurred after surgery. Moreover, radia-tion therapy and chemotherapy had no clear effects on the reconstructed breast.LESSONS:Immediate breast reconstruction surgery by transplanting omental flap for luminal breast cancer patients can be considered successful based on the excellent clinic outcome.

To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide (CGRP) or substance P on repairing bone defects in a rabbit osteoporosis model.

Background: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date.Methods: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing.Results: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22: 29091846, G->A, p.H371Y) was identified in CHEK2, a Li-Fraumeni syndrome causal gene. Examining the status of this novelmutation in the patient's healthy siblings revealed its de novo origin.Conclusion: Our study reports the first case of Li-Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease.

Objective To investigate the diagnosis and treatment of visceral artery aneurysms (VAAs).Methods From June 2008 to December 2013,20 patients (11 male and 9 female) with visceral artery aneurysms were treated in our hospital.The clinical data and treatment outcomes were retrospectively analyzed.Results There were 20 patients,including 11 males and 9 females.The site of aneurysmal disease was splenic artery in 12 cases,mesenteric artery in 2 cases,hepatic artery in 2 cases,renal artery in 2 cases,celiac artery in 1 case and gastroduodenal artery 1 case.10 patients were treated by open surgery,and other 10 patients treated by endovascular.1 patient died,and others were discharged.All patients were followed up 28.5 months (ranged from 10 to 76 months).Two patients died due to cirrhosis of the liver,and the remaining patients were alive,no treatment-related complications,no serious complications,such as aneurysm recurrence occurs.Conclusions Both traditional surgical and endovascular treatment of visceral artery aneurysms may obtain a satisfactory outcome.