Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

BackgroundThe pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking.MethodsA chronic migraine model was established by repeated inflammatory soup stimulation. Mechanical, periorbital, and thermal pain thresholds were assessed by the application of von Frey filaments and radiant heat. The mRNA and protein expression levels of the dopamine D2 receptor were analyzed by qRT‒PCR and western blotting. Colocalization of the dopamine D2 receptor and the GLUA1-containing AMPAR was observed by immunofluorescence. A dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride), a PI3K inhibitor (LY294002), a PI3K pathway agonist (740YP), and a GLUA1-containing AMPAR antagonist (NASPM) were administered to confirm the effects of the dopamine D2 receptor, the PI3K pathway and GULA1 on central sensitization and the GLUA1-containing AMPAR trafficking. Transmission electron microscopy and Golgi-Cox staining were applied to assess the impact of the dopamine D2 receptor and PI3K pathway on synaptic morphology. Fluo-4-AM was used to clarify the role of the dopamine D2 receptor and PI3K signaling on neuronal calcium influx. The Src family kinase (SFK) inhibitor PP2 was used to explore the effect of Src kinase on GLUA1-containing AMPAR trafficking and the PI3K signaling pathway.ResultsInflammatory soup stimulation significantly reduced pain thresholds in rats, accompanied by an increase in PI3K-P110β subunit expression, loss of dopamine receptor D2 expression, and enhanced GLUA1-containing AMPA receptor trafficking in the trigeminal nucleus caudalis (TNC). The dopamine D2 receptor colocalized with the GLUA1-containing AMPA receptor in the TNC; quinpirole, LY294002, and NASPM alleviated pain hypersensitivity and reduced GLUA1-containing AMPA receptor trafficking in chronic migraine rats. Sulpiride aggravated pain hypersensitivity and enhanced GLUA1 trafficking in CM rats. Importantly, the anti-injury and central sensitization-mitigating effects of quinpirole were reversed by 740YP. Both quinpirole and LY294002 inhibited calcium influx to neurons and modulated the synaptic morphology in the TNC. Additional results suggested that DRD2 may regulate PI3K signaling through Src family kinases.ConclusionModulation of GLUA1-containing AMPA receptor trafficking and central sensitization by the dopamine D2 receptor via the PI3K signaling pathway may contribute to the pathogenesis of chronic migraine in rats, and the dopamine D2 receptor could be a valuable candidate for chronic migraine treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01469-x.     

侵袭性垂体腺瘤MRI与肿瘤上皮钙黏蛋白/连接素复合体相关性研究

目的探讨侵袭性垂体腺瘤MRI与肿瘤上皮钙黏蛋白／连接素复合体（E—eadherin catenin complex）在反映肿瘤侵袭性方面的关系。资料与方法在MR图像上对病理证实的31例垂体腺瘤进行测量。根据肿瘤对周围结构的侵袭程度,计算侵袭性累计分数,并将该结果与肿瘤上皮钙黏蛋白／连接素复合体免疫组织化学法染色结果相比较。结果19例腺瘤β连接素（β-catenin）染色结果与累计侵袭分数呈显著线性负相关（r=-0．477,P=0．039）。上皮钙黏蛋白（E—cadherin）和α连接素（α—catenin）染色结果与累计侵袭分数无显著线性相关（分别是r1=-0．018,P=0．930;r2=0．032,P=0．870）。结论侵袭性垂体腺瘤β-catenin表达的减少程度与MRI显示腺瘤侵袭周围结构的程度呈正相关,MRI结合peatenin表达水平可以更好地评价腺瘤的侵袭性。     

美容相关眼部损伤急性期的临床表现

目的：探讨美容相关眼部损伤急性期的临床表现。

方法： 回顾性研究。收集2016-04/2021-10因美容导致的眼部损伤患者53例89眼,分析患者急性期的临床特征,包括性别、年龄、受伤眼别、临床表现、致伤原因、治疗过程及预后。

结果：纳入53例89眼患者均为女性,年龄22-45(平均28.4±6.7)岁。单眼损伤17例,双眼损伤36例。2种或2种以上眼部损伤可累及同一眼。导致眼部损伤的主要美容操作包括：纹眼线38眼(43%); 嫁接睫毛18眼(20%); 去除假睫毛11眼(12%); 涂睫毛膏8眼(9%); 双重睑手术6眼(7%); 其他8眼(9%)。主要眼部损伤类型包括：角膜损伤56眼(63%); 眼睑接触性皮炎26眼(29%); 结膜炎19眼(21%); 眼睑反应性水肿13眼(15%); 眼表异物12眼(14%); 睑缘细菌性感染10眼(11%); 其他5眼(6%),这其中包括因眼周注射玻尿酸导致视网膜中央动脉阻塞1眼(1%)。74眼经过正规治疗可在1-2 wk内痊愈,3眼出现丝状角膜炎,视网膜中央动脉阻塞1眼预后差。

结论：美容相关眼部损伤见于中青年女性,引发眼部损伤最常见的美容操作是纹眼线,最主要损伤类型为角膜损伤。美容相关眼部损伤多数可以预防,治疗方法有效且总体预后良好。     

缺氧诱导因子HIF-1α、3α在血管瘤不同时期的表达和意义

目的 探讨缺氧在血管瘤不同时期的表达和作用.方法 采用免疫组化SP法测定24例增生期血管瘤和18例消退期血管瘤中缺氧染色阳性率,HIF-1α、HIF-3α、VEGF、Ki-67和细胞凋亡表达情况.结果 24例增生期血管瘤中缺氧染色阳性率为80%(19/24),HIF-1α阳性指数为(23.40±4.73)、HIF-3α为(7.90±2.15)、VEGF为(16.90±3.34)、Ki-67为(57.60±11.33)、细胞凋亡指数为(4.50±1.51);而消退期血管瘤中缺氧染色阳性率为90%(16/18),HIF-1α为(9.50±2.67)、HIF-3α为(19.80±2.43)、VEGF为(2.70±0.32)、Ki-67为(11.20±2.65)、细胞凋亡指数为(11.40±2.67).不同时期血管瘤表达的HIF-1α、HIF-3α、VEGF、Ki-67、细胞凋亡指数均有显著性差别(P＜0.05).结论 缺氧是血管瘤不同时期的普遍现象,但对增殖期血管瘤的作用是通过HIF-1α促进内皮细胞繁殖,而对消退期血管瘤是通过HIF-3α促进其凋亡.     

抑郁症患者情绪词识别对照研究

目的：探讨抑郁症患者和正常对照者在进行情绪词识别时的差异。方法：34例在4周内未用药的抑郁症患者和32名正常对照者进行情绪词识别Go/No-Go测验。结果：抑郁症患者正情绪词识别时,反应时显著长于负性情绪词和正常对照组,遗漏数显著多于负性词和正常对照组。结论：抑郁症患者存在负性情绪偏好。     

The Biomarkers for Predicting Viral Hepatitis-Associated Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and more than half of the newly diagnosed cases are chronic hepatitis B patients. Due to the lack of specific clinical manifestations, many patients are already at an advanced stage at the time of diagnosis and therefore have missed the best time for treatment. Organs in a pathological state usually secrete specific substances into the blood, which can indirectly indicate the pathological state of the organ, so some biological markers in the blood can be used as a tool to predict the incidence of HCC.MethodsThe Research articles related to HCC were collected by searching PubMed databases with the keywords “hepatocellular carcinoma”, “serum biomarker”, “hepatitis B”, “prediction” and “prognosis”, and Additional articles were identified by manual search of references found in the primary articles, followed by a summary and review.ResultsViral hepatitis is the main cause of HCC worldwide, and this phenomenon is particularly prominent in Asian and African populations. A variety of serological markers including M2BPGi, IL-6 and COMP can be used to predict the incidence of long-term HCC in patients. The risk of HCC is dynamic rather than constant, and dynamic detection will help improve prediction accuracy. For hepatitis B patients, HBV DNA load and HBcr Ag are important predictive markers of HCC.ConclusionFor a high-risk population of HCC, early risk prediction is helpful to guide clinical work, and timely adjustments of the screening frequency and treatment plan are helpful to prolong the survival time of HCC patients.     

Evaluation of the Immunogenicity in Mice Orally Immunized with Recombinant Lactobacillus casei Expressing Porcine Epidemic Diarrhea Virus S1 Protein

Porcine epidemic diarrhea (PED), characterized by diarrhea, vomiting, and dehydration, is an acute enteric infectious disease of pigs. The disease is caused by porcine epidemic diarrhea virus (PEDV), which infects the intestinal mucosal surface. Therefore, mucosal immunization through the oral route is an effective method of immunization. Lactic acid bacteria, which are acid resistant and bile-salt resistant and improve mucosal immunity, are ideal carriers for oral vaccines. The S1 glycoprotein of PEDV mediates binding of the virus with cell receptors and induces neutralizing antibodies against the virus. Therefore, we reversely screened the recombinant strain pPG-SD-S1/Δupp ATCC 393 expressing PEDV S1 glycoprotein by Lactobacillus casei deficient in upp genotype (Δupp ATCC 393). Mice were orally immunized three times with the recombinant bacteria that had been identified for expression, and the changes of anti-PEDV IgG and secreted immunoglobulin A levels were observed over 70 days. The results indicated that the antibody levels notably increased after oral administration of recombinant bacteria. The detection of extracellular cytokines on the 42nd day after immunization indicated high levels of humoral and cellular immune responses in mice. The above results demonstrate that pPG-SD-S1/Δupp ATCC 393 has great potential as an oral vaccine against PEDV.     

Burst Pressure Prediction of Subsea Supercritical CO2 Pipelines

To improve transportation efficiency, a supercritical CO₂ pipeline is the best choice for large-scale and long-distance transportation inshore and offshore. However, corrosion of the pipe wall will occur as a result of the presence of free water and other impurities present during CO₂ capture. Defects caused by corrosion can reduce pipe strength and result in pipe failure. In this paper, the burst pressure of subsea supercritical CO₂ pipelines under high pressure is investigated. First, a mechanical model of corroded CO₂ pipelines is established. Then, using the unified strength theory (UST), a new burst pressure equation for subsea supercritical CO₂ pipelines is derived. Next, analysis of the material’s intermediate principal stress parameters is conducted. Lastly, the accuracy of the burst pressure equation of subsea supercritical CO₂ pipelines is proven to meet the engineering requirement by experimental data. The results indicate that the parameter b of UST plays a significant role in determining burst pressure of pipelines. The study can provide a theoretical basis and reference for the design of subsea supercritical CO₂ pipelines.     

超声诊断颌下腺炎的临床应用

目的探讨超声诊断颌下腺炎的临床应用价值。方法选取101例经手术证实的颌下腺炎的超声图像,分析颌下腺的大小、形态、内部回声及彩色血流情况。结果101例颌下腺炎中,急性炎症2例,慢性炎症99例,超声与手术病理结果符合率为98%。结论超声对颌下腺炎的诊断准确率较高,并能与颌下区占位性病变相鉴别。