Atherosclerosis is a chronic and progressive inflammatory disease that can lead to adverse cardiovascular and cerebrovascular events. Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a pivotal role in its development and progression, but the upstream regulatory mechanisms remain incompletely defined. Here, we identify ubiquitin-fold modifier 1 (UFM1), a ubiquitin-like protein, as a critical regulator of VSMCs plasticity and atherogenesis. In VSMCs stimulated with oxidized low-density lipoprotein (ox-LDL), UFM1 overexpression markedly attenuated phenotypic switching, restoring contractile features and suppressing synthetic activation, accompanied by reduced proliferation and migration. In contrast, UFM1 knockdown further exacerbated these phenotypic alterations. In ApoE-/- mice, adeno-associated virus (AAV)-mediated UFM1 overexpression attenuated VSMCs phenotypic transition and Ki67-positive cell proliferation and significantly reduced atherosclerotic plaque burden. Transcriptomic analyses revealed the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways as downstream candidates, and subsequent pharmacological inhibition experiments confirmed that the PI3K-AKT signaling pathway is the primary mediator of the protective effects of UFM1. Mechanistically, UFM1 limited AKT phosphorylation, thereby restraining VSMCs dedifferentiation and lesion development. Collectively, these findings highlight the UFM1-AKT axis as a promising therapeutic target for atherosclerotic cardiovascular disease.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the histological images shown in Fig. 2A on p. 117, the 'NC/3 h' and 'NC/6 h' data panels contained an overlapping section of data, suggesting that these data panels were derived from the same original source where different experimental conditions were reported. The authors have been contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in their paper, and we are awaiting their response. Due to the fact that we have been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further.  [International Journal of Molecular Medicine 39: 113‑125, 2017; DOI: 10.3892/ijmm.2016.2809].

BACKGROUND:Diabetic nephropathy (DN) is a life-threatening complication of diabetes mellitus (DM) and the leading cause of end-stage renal disease. Ferroptosis, a novel iron-dependent mode of cell death, has been identified to participate in the pathogenesis of DN. Isorhynchophylline (IRN) is a tetracyclic indole oxide alkaloid present in Uncaria rhynchophylla (Rubiaceae), which shows protective effects against diabetic encephalopathy and acute kidney injury. Our study intends to determine whether IRN ameliorates DN progression through inhibiting ferroptosis. METHODS:The db/db diabetic mice and high glucose (HG)-stimulated human kidney tubular epithelial HK-2 cells were used to explore the potential therapeutic value of IRN in vivo and in vitro. Blood glucose levels, body weight, kidney weight, serum creatinine (SCr), blood urea nitrogen (BUN), and albumin-to-creatinine ratio (UACR) were detected to assess diabetic symptoms and renal functions in db/db mice. Hematoxylin-eosin (H&E) and periodic acid-Schiff staining (PAS) staining were performed to observe renal pathohistological changes in diabetic mice. Iron contents as well as malondialdehyde (MDA) and glutathione (GSH) in mouse tissue homogenates and HK-2 cell supernatants were examined to assess iron accumulation and oxidative stress. The levels of ferroptosis-related proteins and Nrf2/HO-1 signaling-related proteins as well as Nrf2 nuclear translocation in mouse renal tissues and HK-2 cells were detected by western blotting and immunofluorescence staining. RESULTS:IRN administration alleviated diabetic symptoms and improved renal functions in diabetic mice. IRN mitigated renal histologic damage, including glomerular hypertrophy, mesangial matrix accumulation, capillary basement membrane thickening, and thylakoid stroma expansion in diabetic mice. IRN treatment inhibited ferroptosis in both diabetic mice and HG-induced HK-2 cells by reducing iron content and MDA levels, elevating GSH levels, upregulating the protein levels of FTH-1, GPX4, and SLC7A11, and downregulating the protein levels ofTFR-1 and NCOA4. Mechanistically, IRN treatment enhanced Nrf2 and HO-1 protein levels and Nrf2 nuclear translocation in renal tissues of diabetic mice and HG-exposed HK-2 cells. CONCLUSION:IRN plays a renoprotective role in DN by suppressing ferroptosis, which might be ascribed to the Nrf2/HO-1 pathway activation, highlighting the potential therapeutic application of IRN for DN treatment.

BACKGROUND:Obesity-associated adipose tissue dysfunction is a major contributor to metabolic disease. Although obesity is associated with increased glucocorticoid exposure, the role of glucocorticoid receptor (GR) signaling in mature adipocytes during obesity remains unclear. METHODS AND RESULTS:To investigate the direct effects of dexamethasone (Dex) on mature adipocytes, we established an ex vivo culture model of primary human white adipocytes. Dex-mediated GR activation exerted cytoprotective effects by attenuating stress-associated DNA damage, suppressing aberrant cell-cycle re-entry, and downregulating pro-inflammatory programs, thereby preserving adipocyte function. Similar protective effects were observed in adipocytes exposed to sustained high insulin concentrations. In obese human cohorts, elevated circulating adrenocorticotropic hormone levels and increased adipose expression of 11β-hydroxysteroid dehydrogenase type 1 supported the presence of increased glucocorticoid exposure. However, integrated analysis of human adipose single-nucleus RNA-sequencing datasets revealed a significantly higher proportion of GR- unresponsive adipocytes in obesity. Consistently, key GR pathway components, including glucocorticoid receptor (NR3C1), FK506 binding protein 5, and glucocorticoid-induced leucine zipper were significantly downregulated in adipose tissue and mature adipocytes in obesity. These findings were supported by analyses of bulk sequencing datasets from multiple cohorts of obese human adipose tissue. Dataset analyses showed that suppressed GR signaling in obese adipocytes was reversed following sustained weight loss after bariatric surgery. CONCLUSIONS:GR activation protects human adipocytes by restraining cellular stress responses. Obesity-related adipocyte dysfunction is associated with impaired GR signaling despite increased adipose glucocorticoid exposure. These findings support selective GR activation as a potential therapeutic strategy for obesity-related metabolic syndrome.

OBJECTIVES:Unfavorable social risk profile has been identified as a fundamental driver for disparate mortality rate. This study aimed to determine the association between social determinants of health (SDOH) and all-cause or cardiovascular disease (CVD) mortality in patients with chronic kidney disease (CKD). METHODS:Data from adult participants with CKD and available information on SDOH were collected from the 1999-2018 US National Health and Nutrition Examination Survey. SDOH was calculated based on eight factors, including employment, poverty-income ratio, food security, education level, access to healthcare, health insurance, housing instability, and marital status. Cox proportional hazard regression analysis, restricted cubic spline analysis and subgroup analysis were performed. RESULTS:5,420 participants (mean age 58.13 years, 43.04% men) were analyzed, including 729, 1,713, 1,849 and 1,129 with a SDOH of ≤ 2, 3-4, 5-6, and 7-8, respectively. Over a median follow-up of 92 months, 1,923 (742 CVD-related) deaths occurred. Compared to the reference group (SDOH of 7-8), the hazard ratios and 95% confidence intervals for those with a SDOH of 5-6, 3-4, and ≤ 2 were 1.25 (1.06-1.48), 1.51 (1.26-1.81) and 2.00 (1.54-2.60), respectively, for all-cause mortality, and 1.38 (1.08-1.77), 1.43 (1.09-1.89), and 1.78 (1.15-2.77), respectively, for CVD mortality. Restricted cubic spline analysis indicated linear dose-response relationships between SDOH levels and all-cause or CVD mortality. The association between SDOH and mortality was more pronounced in men than in women. CONCLUSION:Lower SDOH levels are independently associated with higher all-cause and CVD mortality rates among US adults with CKD, especially in men.

Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel–Lindau-mediated K48-linked ubiquitin–proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin–proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.

Background Thyroid cancer is one of the most common malignant tumors of the endocrine system. Studies have demonstrated that maslinic acid (MA) has a wide range of antitumor activities via multiple cellular pathways. However, the role of MA in thyroid cancer remains poorly investigated. Objective To investigate the effects and underlying mechanisms of MA on thyroid cancer cells. Results MA inhibited cell viability and increased apoptosis in TPC1 and Cal62 cells. MA promoted apoptosis in TPC1 and Cal62 cells in a dose-dependent manner evidenced by flow cytometry and Western blotting. In addition, treatment with MA increased the expression of endoplasmic reticulum (ER) stress markers, such as Binding-immunoglobulin protein (BIP) and C/EBP homologous protein 10 (CHOP), in thyroid cancer cells. In cells treated with 4-phenylbutyric acid, an inhibitor of ER stress, MA-induced apoptosis was partially reversed. Finally, treatment with MA inhibited thyroid cancer growth in a TPC1 cell xenograft model. Conclusion Results indicated that MA promoted apoptosis in thyroid cancer cells via ER stress. These findings may provide new insights into novel therapeutic strategies for thyroid cancer.

A recent letter published in this journal provided the data of COVID-19 naturally recovered cases at the Fangcang shelter hospital, a type of basic medical facility converted from public space to handle asymptomatic cases or low-risk patients with mild symptoms, during the current Omicron outbreak in Shanghai.1 Since early 2022, the fasting spread of the SARS-CoV-2 Omicron variant has fueled a surge in newly-diagnosed cases across China, with the majority occurring in Shanghai.2 According to the Shanghai Municipal Health Commission, as of May 4, 2022, more than 600,000 people have been infected, most of them with the Omicron BA.2 variant.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease characterized by lipid accumulation and endoplasmic reticulum (ER) stress, while effective therapies targeting the specific characteristics of NAFLD are limited. Ufmylation is a newly found post-translational modification process that involves the attachment of the Ubiquitin-fold modifier 1 (UFM1) protein to its substrates via ufmylation modification system. Ufmylation regulates ER stress via modifying UFM1 binding protein 1 (UFBP1), suggesting a potential role for ufmylation in NAFLD pathogenesis. However, the precise role of ufmylation in NAFLD remains unclear. Herein, we aim to elucidate the impact of ufmylation on UFBP1 in NAFLD and explore the underlying mechanisms involved. We observed increased expression of UFM1-conjugated proteins and ufmylation modification system components in livers with steatosis derived from NAFLD patients and NAFLD models. Upregulation of ufmylation on hepatic proteins appeared to be an adaptive response to hepatic ER stress in NAFLD. In vitro, knocking down UFBP1 resulted in increased lipid accumulation and lipogenesis in hepatocytes treated with free fatty acids (FFA), which could be rescued by wild-type UFBP1 (WT UFBP1) but not by a mutant form of UFBP1 lacking the main ufmylation site lys267 (UFBP1 K267R). In vivo, ufmylation on UFBP1 ameliorated obesity, hepatic steatosis, hepatic lipogenesis, dyslipidemia, insulin resistance and liver damage in mice with NAFLD induced by a high fat diet (HFD). We also demonstrated that the downregulation of UFBP1 induced ER stress, whereas the reintroduction or overexpression of UFBP1 alleviated ER stress in a manner dependent on ufmylation in NAFLD. This mechanism could be responsible for the amelioration of aberrant hepatic lipogenesis and insulin resistance in NAFLD. Our data reveal a protective role of ufmylation on UFBP1 against NAFLD and offer a specific target for NAFLD treatment.

BACKGROUND:Lung adenocarcinoma (LUAD) is one of the major types of lung cancer with high morbidity and mortality. The TRAF-interacting protein (TRAIP) is a ring-type E3 ubiquitin ligase which has been recently identified to play pivotal roles in various cancers. However, the expression and function of TRAIP in LUAD remain elusive. METHODS:In this study, we used bioinformatic tools as well as molecular experiments to explore the exact role of TRAIP and the underlying mechanism. RESULTS:Data mining across the UALCAN, GEPIA and GTEx, GEO and HPA databases revealed that TRAIP was significantly overexpressed in LUAD tissues than that in adjacent normal tissues. Kaplan-Meier curve showed that high TRAIP expression was associated with poor overall survival (OS) and relapse-free survival (RFS). Univariate and multivariate cox regression analysis revealed that TRAIP was an independent risk factor in LUAD. And the TRAIP-based nomogram further supported the prognostic role of TRAIP in LUAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that TRAIP-associated genes were mainly involved in DNA replication, cell cycle and other processes. The immune infiltration analysis indicated that TRAIP expression was tightly correlated with the infiltration of diverse immune cell types, including B cell, CD8 + T cell, neutrophil and dendritic cell. Moreover, TRAIP expression was observed to be significantly associated with tumor infiltrating lymphocytes (TILs) and immune checkpoint molecules. In vitro experiments further confirmed knockdown of TRAIP inhibited cell migration and invasion, as well as decreasing chemokine production and inhibiting M2-like macrophage recruitment. Lastly, CMap analysis identified 10 small molecule compounds that may target TRAIP, providing potential therapies for LUAD. CONCLUSIONS:Collectively, our study found that TRAIP is an oncogenic gene in LUAD, which may be a potential prognostic biomarker and promising therapeutic target for LUAD.

Objective:To investigate the relationship and significance of serum uric acid (UA) level and the Framingham 10-year risk of coronary heart disease in patients with type 2 diabetes mellitus (T2DM).Methods:904 patients with T2DM who were admitted to the Department of Endocrinology, Ninth People′s Hospital (North Hospital) , Shanghai Jiaotong University School of Medicine, from August 2015 to December 2017 were chosen, the serum UA levels and Framingham 10-year risk of coronary heart disease between men and women with T2DM were compared. Patients were divided into 4 groups based on quantiles of serum UA level, Framingham 10-year risk of coronary heart disease, and other indicators were compared. T2DM patients were divided into low-risk group, medium-risk group and high-risk group based on their Framingham risk scores for 10-year coronary heart disease, and serum UA levels and other indicators in each group were compared and analyzed. The risk factors for coronary heart disease in the Framingham 10-year were investigated using Logistic regression.Results:Men with T2DM had higher serum UA levels [340.00(287.00, 393.00)μmol/L] and a higher Framingham 10-year coronary heart disease risk [20(13, 31)%] than women [305.00(255.00, 365.50)μmol/L, 15(10, 20)%], and the differences were statistically significant (Z=-6.22, -7.01, all P<0.01). Based on serum UA level quartiles, Framingham 10-year coronary heart disease risk was 15(8, 20)%, 16(10, 20) %, 20(13, 25) %, and 20(13, 31)% from group 1 to group 4, respectively. Patients with higher serum UA levels had a significantly higher 10-year risk of coronary heart disease (P<0.05). Patients in the higher Framingham 10-year risk groups had significantly higher serum UA levels (P<0.05). According to a Logistic regression analysis, serum UA level was an independent factor in the Framingham 10-year risk of coronary heart disease (P=0.022, OR=1.003, 95%CI: 1.000-1.006).Conclusion:Serum UA level is an independent factor in Framingham 10-year risk of coronary heart disease in patients with T2DM, at the same time, serum UA level is positively associated with the Framingham 10-year risk degree of coronary heart disease in T2DM.

Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule (UBLs), is evolutionarily expressed in multiple species except yeast. Similarly to ubiquitin, UFM1 is covalently attached to its substrates through a well-orchestrated three-step enzymatic reaction involving E1, the UFM1-activating enzyme (ubiquitin-like modifier-activating enzyme 5, UBA5); E2, the UFM1-conjugating enzyme 1 (UFC1); and E3, the UFM1-specific ligase 1 (UFL1). To date, numerous studies have shown that UFM1 modification is implicated in various cellular processes, including endoplasmic reticulum (ER) stress, DNA damage response and erythroid development. An abnormal UFM1 cascade is closely related to a variety of diseases, especially tumors. Herein, we summarize the process and functions of UFM1 modification, illustrating the relationship and mechanisms between aberrant UFMylation and diversified tumors, aiming to provide novel diagnostic biomarkers or therapeutic targets for cancer treatments.

Macrophage activation is an essential component of systemic chronic inflammation and chronic inflammatory diseases. Emerging evidence implicates miR-185-5p in chronic inflammation diseases. However, the regulatory role of miR-185-5p in macrophage pro-inflammatory activation has not been studied previously. Here, we identified that miR-185-5p was one of the top genes and effectively downregulated in two macrophage miRNA expression datasets from GEO. Under LPS stress, miR-185-5p overexpression reduced pro-inflammatory cytokine expression, suppressed phagocytosis in RAW264.7 macrophage. miR-185-5p inhibitors augmented pro-inflammatory effects of LPS in macrophage. Mechanically, miR-185-5p sponged and negatively regulated the protein expression of CDC42. Ablation of CDC42 with selective CDC42 inhibitor CASIN reversed the pro-inflammatory effect of miR-185-5p inhibitors through inhibiting MAPK/JNK pathways. Collectively, these data demonstrate that miR-185-5p exhibited anti-inflammatory functions in LPS-induced RAW264.7 macrophages at least partially through CDC42/JNK pathways. Our findings yield insights into the understanding of miR-185-5p-regulated network in macrophages inflammation, which is beneficial for exploring miRNA-protein interaction in atherosclerotic inflammation.

UFMylation is a ubiquitin-like modification which attaches the ubiquitin-fold modifier 1 to target proteins. To date, only a few UFMylation targets have been identified. In the current study, we demonstrated that P4HB is a new target protein for UFMylation and it can be UFMylated at three lysine residues in the form of mono-UFMylation. P4HB has oxidoreductase, chaperone and isomerase effects. It presents in the endoplasmic reticulum, mitochondria and cytosol. Next, we generated a stable HepG2 cell line, the hepatocellular cells, with defective P4HB UFMylation. Our data show that P4HB UFMylation defect promotes P4HB protein degradation via the ubiquitin-proteasome pathway. Defective P4HB UFMylation causes mitochondrial function damage, oxidative stress, and endoplasmic reticulum stress in HepG2 cells. These effects are more obvious when treating HepG2 cells with palmitic acid, which is frequently used as one of the cell models of non-alcoholic fatty liver disease (NAFLD). Our results identify UFMylation as a key post-translational modification for the maintenance of P4HB stability and biological functions in HepG2 cells, and point to P4HB UFMylation as a potential direction in the study of NAFLD.

钠-葡萄糖共转运蛋白2(sodium-glucose cotransporter 2,SGLT2)抑制剂是一类新型非胰岛素依赖性降血糖药物,其主要通过抑制近端肾小管对葡萄糖的重吸收,促进葡萄糖从尿液排泄,从而产生降低患者血糖水平的作用.SGLT2抑制剂不仅能改善2型糖尿病患者的高血糖状态,且还具有减轻体质量,降低血压,以及减少心血管事件发生和保护肾脏的效果.当然,SGLT2抑制剂也存在一些不良反应.本文就SGLT2抑制剂的不良反应及其预防作一概要介绍.

Objective:To investigate the effects of once-weekly dulaglutide 1.5 mg treatment on glucose variability and glucose control in type 2 diabetes patients using 24 h continuous glucose monitoring (CGM) technology.Methods:A multi-center, prospective study was carried out. A total of 149 type 2 diabetes patients were recruited, who were treated with dulaglutide for 2 to 4 weeks, wearing CGM devices to monitor the glucose level. The primary evaluation indicators included mean amplitude of glycemic excursions (MAGE), mean daily glucose (MDG), time in target glucose range (TIR), time above range and time below range (TAR, TBR). Secondary indicators included change of concomitant medication dosages, treatment-related adverse events and change of blood pressure. Mixed effects model (MEM) of repeated measurement data or paired Mann-Whitney rank-sum test was used to analysis the differences between CGM parameters in each week during the treatment period.Results:MDG and MAGE of patients decreased by (0.76±0.31) and (0.50±0.13) mmol/L ( P<0.05), respectively, after the 4-week dulaglutide treatment. When compared with the first week, time in range (TIR) in week 2 increased from 73.91% (IQR 25.20%) to 7.49% (IQR 24.89%), and the mean difference was 3.58% ( P<0.01). Time in hyperglycemia decreased from 2.95% (IQR 10.76%) to 1.94% (IQR 7.24%), and the median difference was 1.01% ( P<0.001), while the time in hypoglycemia did not change ( P>0.05). Mean systolic pressure of patients decreased by (5.2±1.5) mmHg (1 mmHg=0.133 kPa) after the first-week treatment. Furthermore, 14 patients reported treatment-related adverse events including gastrointestinal reaction and hypoglycemia. Conclusions:Treatment with dulaglutide 1.5 mg weekly for 2 to 4 weeks could significantly reduce glycemic variability, improve short-term glucose control and lower blood pressure in type 2 diabetes patients without significantly increasing the risk of hypoglycemic events.

目的 探讨德谷胰岛素联合胰高血糖素样肽-1受体激动剂(GLP-1 RAs)对2型糖尿病患者网膜素-1(Omentin-1)、丝氨酸蛋白酶抑制剂(Vaspin)、视黄醇结合蛋白4(RBP4)水平的影响.方法 选取2019年7月至2020年7月收治的2型糖尿病患者172例,随机分为GLP-1组和联合治疗组,每组86例.GLP-1组采用GLP-1 RAs利司那肽治疗,联合治疗组采用德谷胰岛素联合GLP-1 RAs利司那肽治疗,采用酶联免疫吸附试验(ELISA)检测Omentin-1、Vaspin、RBP4、糖类抗原199(CA199)、糖类抗原125(CA125)水平,采用糖化血红蛋白自动分析仪检测空腹血糖(FBG)、餐后2 h血糖(2 hPBG)、糖化血红蛋白(HbA1c)水平,采用Botnia钳夹术检测胰岛素β细胞(HOMA-B)、胰岛素抵抗指数(HOMA-IR),比较2组治疗效果并观察不良反应.结果 与GLP-1组相比,联合治疗组Omentin-1水平明显升高,Vaspin、RBP4水平明显降低(P<0.05).与GLP-1组相比,联合治疗组2 hPBG、HbA1c、FBG水平明显下降(P<0.05).与GLP-1组相比,联合治疗组HOMA-IR水平明显下降,HOMA-β水平明显上升(P<0.05).与GLP-1组相比,联合治疗组CA125、CA199水平明显降低(P<0.05).与GLP-1组相比,联合治疗组治疗总有效率较高(P<0.05).与GLP-1组相比,联合治疗组总不良反应略高,但差异无统计学意义(P>0.05).结论 联合应用德谷胰岛素、GLP-1 RAs利司那肽治疗2型糖尿病患者可有效升高Omentin-1水平,降低Vaspin、RBP4及血糖水平,效果显著.

目的:探讨2型糖尿病患者心率变异性(HRV)时域及频域参数与颈动脉粥样硬化(CAS)患病风险的相关性.方法:根据纳入与排除标准共收集2019年7月至2021年8月上海交通大学医学院附属第九人民医院内分泌代谢科住院的377例2型糖尿病患者的临床资料,并通过3分钟的心电图记录HRV时域[R-R间隔的标准差(SDNN)、相邻R-R间隔差值的均方根(RMSSD)、相邻R-R间隔差值＞50 ms的数目占所有R-R间隔总数百分比(PNN50)]和频域[低频功率(LF)、高频功率(HF)、LF/HF、总功率(TP)]参数.根据颈动脉超声有无斑块形成分为无CAS组和CAS组,分析其与HRV各参数的关系.结果:与无CAS组相比,CAS组年龄、心血管疾病、体质量指数(BMI)、糖化血红蛋白A1c(HbA1C)、甘油三酯(TG)水平明显升高,舒张压(DBP)、空腹血糖(FPG)水平降低,差异具有统计学意义(P＜0.05).CAS组大多数HRV参数低于无CAS组,包括SDNN、RMSSD、PNN50、LF、LF/HF、TP,差异有统计学意义(P＜0.05或P＜0.01).SDNN与年龄、病程、心血管疾病、饮酒呈负相关(P＜0.05或P＜0.01);RMSSD与病程、饮酒呈负相关(P＜0.05或P＜0.01);PNN50与病程呈负相关(P＜0.05);LF与年龄、病程、心血管疾病呈负相关,与DBP、低密度脂蛋白(LDL)呈正相关(P＜0.05或P＜0.01);HF与年龄、病程呈负相关,与LDL呈正相关(P＜0.05或P＜0.01);LF/HF与年龄、心血管疾病、TG呈负相关(P＜0.05或P＜0.01);TP与年龄、病程、心血管疾病呈负相关,与DBP、LDL呈正相关(P＜0.05或P＜0.01).使用多因素logistic回归对部分可能的混杂因素进行校正后,SDNN、RMSSD、LF、LF/HF、TP降低仍然与CAS发生的风险增加相关(均P＜0.05).进一步按糖化血红蛋白(≤7.0％、＞7.0％)分层后分析,糖化血红蛋白＞7.0％组的患者SDNN、RMSSD、LF、TP的降低与CAS发生的风险增加相关(P＜0.05),而在糖化血红蛋白≤7.0％组,仅RMSSD、PNN50有统计学意义(P＜0.05).结论:2型糖尿病患者HRV参数SDNN、RMSSD、LF、TP降低与CAS发生的风险增加有关,且糖化血红蛋白＞7.0％的患者有更多的HRV参数(SDNN、RMSSD、LF、TP)与 CAS相关.

目的 探讨自制血小板凝胶联合常规方法治疗糖尿病足的临床疗效.方法 选取海南西部中心医院2018年8月至2021年8月收治的糖尿病足患者105例,按随机数字表法分为观察组(53例)和对照组(52例).两组患者均予常规降糖、抗感染治疗,观察组患者加用自制血小板凝胶治疗,均连续治疗3个月.结果 观察组总有效率为92.45％,显著高于对照组的76.92％(P<0.05).治疗后,观察组患者的血管内皮生长因子,碱性成纤维细胞生长因子、胰岛素样生长因子-1水平均显著高于对照组(P<0.05);观察组患者的单核细胞趋化蛋白-1、Toll样受体4、高迁移率族蛋白1水平均显著低于对照组(P<0.05);观察组患者的糖尿病患者生存质量特异性量表(DMQLS)评分显著高于对照组(P<0.05).观察组与对照组的不良反应发生率相当(9.43％比15.38％,P>0.05).结论 自制血小板凝胶联合常规方法治疗糖尿病足,可提升生长因子水平,降低炎性因子水平,提高患者的生活质量.

Hepatocellular carcinoma (HCC) is one of the most common subtypes of malignant liver tumors, characterized by high morbidity and mortality. Due to its poor diagnosis strategy and inefficient clinical intervention, HCC has brought terrible life experiences for patients worldwide. Finding novel curative agents for HCC is urgently needed. In the current study, we hypothesized that lncRNA PANTR1 participates in HCC initiation or progression. Our study found that lncRNA PANTR1 was upregulated in HCC tumor tissues and abundantly expressed in HCC cell lines. PANTR1 knockdown inhibited cell growth and migration, promoted cell apoptosis in vitro, and suppressed tumor cell growth in vivo. Moreover, our results suggest that downregulated PANTR1 inhibited the Warburg effect in HCC cells. Underlying mechanisms of PANTR1 in HCC progression were investigated. PANTR1 acted as a competent sponge for miR-587 and downregulated miR-587 expression in HCC cells. Further, MiR-587 directly targets BCL2A1. lncRNA PANTR1 promotes HCC progression via mediating the miR-587-BCL2A1 axis. Our study identified a novel lncRNA PANTR1/miR-587/BCL2A1 axis in HCC progression. We might provide a new target for HCC basic research and clinical management.