MicroRNA and long noncoding RNA involvement in gout and prospects for treatment

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are both types of noncoding RNA. They have been demonstrated to be involved in the regulation of various human inflammatory diseases and can be used as biomarkers for disease diagnosis and prognosis, and even be developed into new drugs. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Recent studies have shown that miRNAs and lncRNAs mediate the progress of gout. Based on the pathogenesis of gout, including hyperuricemia, MSU deposition, acute gouty arthritis and gouty bone erosion, this paper reviewed the role of miRNAs and lncRNAs in the processes and the possible therapeutic targets of miRNAs and lncRNAs in gout.     

Clinical differentiation between acute renal infarction and acute ureteral stone in the emergency department: A single-center retrospective case-control study

BackgroundFew studies have compared renal infarction (RI) and ureteral stone (US), so there is insufficient evidence for emergency clinicians (ECs) to quickly suspect RI during the first assessment. Therefore, we compared the initial clinical presentation and laboratory findings of these diseases in the emergency department (ED) to determine a factor that may indicate RI.MethodsThis single-center retrospective case-control study included 42 patients with acute RI and 210 with US who visited the ED from 2014 to 2020. Medical record data from first ED arrival were investigated, and clinical presentations, blood and urine test results obtained in the ED were compared and analyzed using logistic regression analysis.ResultsECs never suspected the initial diagnosis of RI as RI. The most common initial diagnosis was US (40.5%). Among patients with US, 150 patients (71.4%) were suspected of having US (p < 0.001). Abdominal pain (61.9%) was the most common chief complaint in the RI group, and flank pain (73.8%) was the most common in the US group (p < 0.001). 27 factors showed significant differences between the groups. Among those, age ≥ 70 years (odds ratio [OR]: 311.2, 95% confidence interval [CI]: 2.0–47,833.1), history of A-fib (OR: 149872.8, 95% CI: 289.4–7.8E+07), fever ≥37.5 °C (OR: 297.3, 95% CI: 3.3–27,117.8), Cl⁻ ≤ 103 mEq/L (OR: 9.0, 95% CI: 1.0–80.1), albumin ≤4.3 g/dL (OR: 26.6, 95% CI: 2.1–330.3), LDH ≥500 IU/L (OR: 17.9, 95% CI: 1.8–182.5), and CRP ≥0.23 mg/dL (OR: 7.5, 95% CI: 1.1–52.3) showed significantly high ORs, whereas urine RBCs (OR: 0, 95% CI: 0–0.02) showed a low OR (p < 0.05). The regression model showed good calibration (chi-square: 6.531, p = 0.588) and good discrimination (area under the curve = 0.9913).ConclusionsWhen differentiating acute RI from US in the ED, age ≥ 70 years, history of A-fib, fever ≥37.5 °C, LDH ≥500 IU/L, Cl⁻ ≤ 103 mEq/L, albumin ≤4.3 g/dL, CRP ≥0.23 mg/dL and negative urine RBC result suggest the possibility of RI.     

Role of thoracic and abdominal tomography in identifying a potential source of infection in patients with acute fever of unknown focus

ObjectivesThe objective of this study was to evaluate the relationship between clinical features and the presence of infection on thoracic and abdominal tomography (CT) scans in emergency department (ED) patients with acute febrile illness without apparent source.MethodsPatients aged 18 years and over who presented to ED with acute fever of unknown origin between January 1, 2020 and December 31, 2020 and underwent CT imaging (thoracic and abdomen) as a diagnostic test were included in the study retrospectively. Acute fever of unknown origin was defined as the absence of a history or physical examination finding that could explain the possible cause of fever, normal values of parameters that would suggest an infection in the urine analysis, and absence of infiltration on chest X-ray. The patients were divided into two groups according to the presence and absence of a source of infection on CT. The clinical and demographic data of the patients were evaluated. The effect of clinical factors on the presence of infection in CT scans was determined using the logistic regression analysis.ResultsAmong the 173 patients included in the study, the CT scans were positive for the source of infection in 31.2% (n = 54) and negative in 68.8% (n = 119). In the multiple logistic regression analysis, age ≥ 65 years [odds ratio (OR): 2.72, 95% confidence interval (CI):1.15–4.35, p < 0.001), presence of comorbidity (OR:2.37, 95%CI:1.08–4.14, p = 0.033), and procalcitonin positivity (PCT) (OR: 2.54, 95%CI: 1.29–4.95, p = 0.006) were identified as risk factors for the presence of infection in CT.ConclusionPatient's age, presence of comorbidity and PCT level should be considered when deciding on the use of CT in determining the source of infection in acute febrile patients without clinical clues.     

The association between the disruption of motor imagery and the number of depressive episodes of major depression

Background

Mental rotation performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. Previous studies suggest depressive patients present the correlates of impaired behavioural performance for mental rotation and psychomotor disturbance. The aim of this study is to compare the mental rotation abilities of patients with a first episode of depression, recurrent depression and healthy control subjects with regard to hand tasks.

Methods

We tested 32 first episode of depression, 38 recurrent depression and 36 healthy control subjects by evaluating the performance of depressed patients with regard to the hand mental rotation tasks.

Results

First, the first episode and recurrent depression subjects were significantly slower and made more errors than controls in mentally rotating hands. Second, the first depressive episode but not the recurrent depression displayed the same pattern of response times to stimuli at various orientations relative to control subjects in the hand task. Third, in particular, recurrent depression subjects were significantly slower and made more errors during the mental transformation of hands than first depressive episode relative to control subjects and the differences were significantly larger in female than male subjects in the mental rotation hand task.

Limitations

Patients were on antidepressant medication.

Conclusions

These results suggest that the impaired behavioural performance for mental representation processing are related to the number of previous episodes. Moreover, the recurrent major depressive episodes may contribute to the reinforcement of cognitive impairments and further the development or maintenance of mental representation dysfunctions, especially in female patients. A deficit on mental rotation in the depressive patients may be potential biomarkers for recurrence chronically.     

微波消融联合载阿霉素微泡靶向击破在小鼠H22肝癌治疗中的效果观察

【摘要】 目的 观察微波消融（MWA）联合载阿霉素微泡靶向击破治疗小鼠H22肝癌皮下瘤的效果。 方法 制备空白微泡和载阿霉素微泡,检测其理化特性。流式细胞仪分析不同给药方式下体外细胞内药物浓度。构建BALB/c小鼠H22肝癌皮下瘤模型,将72只荷瘤小鼠随机均分为单纯MWA组（A组）、MWA+阿霉素组（B组）、MWA+空白微泡组（C组）、MWA+载阿霉素微泡组（D组）,其中C、D组微泡经低频超声击破。记录小鼠肿瘤体积变化,构建Kaplan-Meier生存曲线,比较心、肾组织内药物浓度。病理切片检测各组残存活性肿瘤区微血管密度（MVD）和Ki-67表达,并进行统计学分析。结果 体外细胞实验显示,低频超声靶向击破微泡技术能显著提高肿瘤细胞内药物浓度（P=0.011）;体内实验显示,D组抑制肿瘤生长显著优于A组（P=0.008 5）,B组、D组小鼠生存时间均比A组显著延长（P=0.009,P=0.003）,同时D组心、肾组织内药物浓度均显著降低（P=0.012,P=0.045）。D组残存活性肿瘤区MVD与A组相比显著降低（P＜0.000 1）,B、D组肿瘤细胞Ki-67表达均显著降低（P＜0.001）。结论 MWA联合载阿霉素微泡超声靶向击破可提高肝癌细胞内药物浓度,抑制肿瘤增殖和微血管生成,弥补单纯MWA治疗适形性不足,同时降低药物心、肾不良反应。     

Formononetin Inhibited the Inflammation of LPS-Induced Acute Lung Injury in Mice Associated with Induction of PPAR Gamma Expression

Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice.     

Paeoniflorin Attenuates Lipopolysaccharide-Induced Permeability of Endothelial Cells: Involvements of F-Actin Expression and Phosphorylations of PI3K/Akt and PKC

This study aimed to investigate the effects of paeoniflorin, the main active ingredient of the medicinal plant Paeonia lactiflora Pall., on the permeability of endothelial cells induced by lipopolysaccharide (LPS) and the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were stimulated by LPS. Extravasated FITC-dextran reflecting permeability was assessed by multimode microplate reader, and the migration of bis-carboxyethyl-carboxyfluorescein acetoxy-methyl-labeled human acute monocytic leukemia cell line and leukemia cell line cells through HUVECs were analyzed by fluorescence microscopy. The phosphorylations of phosphatidylinositol 3-kinase (PI3K)/Akt, protein kinase C (PKC), and cofilin in HUVECs were assessed by western blotting, and the F-actin level was detected by laser scanning confocal microscopy. After LPS stimulation, inflammatory endothelial cells exhibited significantly increased permeability. Paeoniflorin (10, 30, and 100 μM) inhibited dextran extravasation and leukocyte migration through HUVECs induced by LPS in a concentration-dependent manner. Moreover, paeoniflorin was able to suppress the phosphorylations of PI3K/Akt, PKC, and cofilin, as well as F-actin reorganization in HUVECs induced by LPS. These findings revealed that paeoniflorin partly blocked LPS-induced endothelium permeability, supporting a new explanation for its anti-inflammatory effects.     

甲氟喹对胶质瘤细胞的放射增敏作用

目的:研究甲氟喹对胶质瘤细胞的放射增敏作用,并对其机制进行初步探索。方法:取指数生长期的胶质瘤U251细胞,采用CCK-8检测法研究甲氟喹作用后U251细胞的存活率;细胞克隆形成实验评估甲氟喹对U251细胞的放射增敏效果;流式细胞技术检测甲氟喹联合X射线作用后U251细胞的活性氧水平和细胞凋亡率,探索联合作用下U251细胞的死亡机制。结果:甲氟喹对胶质瘤细胞具有良好的放射增敏效果,其对U251细胞的最大放射增敏比为1.64。X射线联合甲氟喹作用于U251细胞后,细胞的凋亡水平增加,活性氧水平增加,活性氧抑制剂谷胱甘肽能抑制X射线联合甲氟喹作用诱导的U251细胞凋亡。结论:甲氟喹对U251细胞有放射增敏作用,其作用机制可能为通过增加细胞活性氧水平、诱导细胞凋亡导致放射敏感性增加。     

调强放射治疗“end to end”质量控制核查中应用针尖电离室测量小野剂量的初步研究

目的:在调强放射治疗“end to end”质量核查中,探讨应用针尖电离室对调强放射治疗小野照射进行绝对剂量测量的研究。方法:选择3省20家医院,将放有热释光剂量计TLD（距模体表面距离约7.5 cm）和胶片的国际原子能机构（IAEA）模体进行CT扫描,图像导入放射治疗计划系统（TPS）中,设计治疗计划,进行7野等中心调强照射,MLC照射野大小>2 cm×2 cm且<4 cm×4 cm。同时针尖电离室（0.015 cc）放在固体水模体距模体表面7.5 cm下进行点剂量绝对剂量验证:（1）将治疗计划中射野角度归零平移到固体水模体中进行剂量验证;（2）治疗计划射野角度不归零时为实际治疗照射方向,平移到固体水模体中进行绝对剂量验证。结果:在调强放射治疗多叶光栅小野照射的固体水模体中,用针尖电离室测量的绝对剂量与TPS计算得到的绝对剂量比较,7野照射方向归为零度时,比较偏差<5%;实际照射方向时,比较偏差<5%。验证后的计划,在IAEA模体上进行实际7野调强治疗,模体中的高剂量靶区胶片（Gafchromic EBT3 film）绝对剂量通过率均≥90%（Gamma分析:3%, 3 mm）,TLD偏差<7%。均符合IAEA提出的标准。结论:在调强放射治疗多叶光栅小野照射时,可以应用针尖电离室作为绝对剂量验证的一个方法。     

妊娠期糖尿病患者血清FAP4、25(OH)D水平与新生儿结局的关系

目的探究妊娠期糖尿病(GDM)患者血清脂肪酸结合蛋白质4(FAP4)、25-羟维生素D[25(OH)D]水平与新生儿结局的关系。方法选取2018年3月至2020年4月本院收治的GDM患者102例(观察组),另选取同期在本院生产的健康孕妇83例(对照组),比较两组的血脂相关指标、血糖相关指标、胰岛素抵抗指数(HOMA-IR)、血清FABP4、25(OH)D水平,采用受试者工作特征(ROC)曲线分析血清FABP4、25(OH)D水平预测新生儿结局的应用价值。结果观察组的总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FPG)和餐后2 h血糖(2 h PG)水平均高于对照组,高密度脂蛋白胆固醇(HDL-C)和HOMA-IR水平均低于对照组,差异有统计学意义(P<0.05);两组的胎儿窘迫、胎儿生长受限、新生儿窒息和低体重出生发生率比较差异无统计学意义(P>0.05),观察组的新生儿不良结局总发生率高于对照组,差异有统计学意义(P<0.05);观察组的血清FABP4水平高于对照组,25(OH)D水平低于对照组,差异有统计学意义(P<0.05);观察组两亚组患者血清FABP4、25(OH)D水平比较,结局不良组患者的血清FABP4水平明显高于结局良好组,25(OH)D水平明显低于结局良好组,差异有统计学意义(P<0.05);ROC曲线分析结果显示,FABP4、25(OH)D的曲线下面积(AUC)分别为0.660和0.715,对新生儿结局均有一定的预测能力(P<0.05)。结论 GDM患者血清FABP4、25(OH)D水平与新生儿不良结局有关,二者对GDM患者新生儿不良结局具有一定的预测价值。