Detection rate and shunt grading with synchronous testing of contrast transcranial Doppler and contrast transthoracic echocardiography: Preliminary findings.

Patent foramen ovale, a common congenital atrial septal defect, may lead to cardiac right-to-left shunting (RLS), which has been associated with various diseases. Reliable techniques for detecting RLS are essential for diagnosis and assist with treatment decision-making. Contrast transcranial Doppler (c-TCD), contrast transthoracic echocardiography (c-TTE), and contrast transesophageal echocardiography can be used to detect RLS. However, it is still unclear which ultrasound modalities are the most practical and cost-effective. To evaluate the efficacy of synchronous c-TCD and c-TTE in detecting cardiac RLS. We prospectively designed and continuously recruited 100 patients with cryptogenic stroke, migraines, transient ischemic attack, unexplained syncope, or dizziness admitted at the First Affiliated Hospital of Shenzhen University between February 2020 and August 2020. Ninety-five patients underwent synchronous c-TCD and c-TTE (during a single contrast-enhanced ultrasound session). We compared synchronous test results with the results of c-TCD alone and c-TTE alone. Ninety-five patients successfully underwent synchronous c-TCD and c-TTE, with the data analyzed for each individual. The positive detection rates of Grade I, II, and III shunts with synchronous c-TCD and c-TTE were higher than those with c-TTE or c-TCD alone (P = .047, P = .002, and P = .024, respectively). Overall, the positive detection rates of synchronous tests, c-TCD alone, and c-TTE were 69.5%, 51.6%, and 31.6%, respectively (P = .000, and P = .012). Among the 66 patients who were double-RLS-positive (both c-TTE and c-TCD showed positive results), as detected by the synchronous test, 26 (39.3%) patients who underwent c-TTE alone had higher shunt grades detected than those who underwent c-TCD alone. Conversely, 5 (7.6%) patients who underwent c-TCD alone had higher shunt grades detected than those who underwent c-TTE alone (P = .000). Synchronous c-TCD and c-TTE testing can significantly improve the detection rate, accuracy, and test process efficacy for quantifying RLS, and reduce the testing risk, workload, and medical costs.

Efficacy and safety of intensified antithrombotic therapy followed by stenting in treatment of highly severe stenosis accompanied by thrombosis in carotid atherosclerosis.

OBJECTIVE: This study explored the efficacy and safety of intensified antithrombotic therapy followed by stenting in treatment of highly severe stenosis accompanied by thrombosis in patients with carotid atherosclerosis (CAS). METHODS: This study recruited a total of 24 CAS patients between June 2016 and November 2020 in the research group, who had highly severe stenosis accompanied by in situ thrombosis and were treated with intensified antithrombotic treatment followed by stenting. The control group included 17 patients treated with stent angioplasty immediately after diagnosis with stenosis and thrombosis between January 2012 and May 2016. The efficacy and safety of treatment were compared between these two groups. RESULTS: The thrombus completely disappeared in 22 out of 24 patients (91.67%) in the research group after intensified antithrombotic treatment followed by stenting. Two patients still had the thrombus, but the volume was significantly reduced compared to that pre-treatment. The incidence of clinical events and new infarctions in the research group was significantly lower than that in the control group. In addition, the research group had significantly lower incidence of embolus antedisplacement and blocking the emboshield during the operation than the control group. There were no significant differences in the incidence of long-term complications and mortality between these two groups. The clinical prognosis of patients in the research group was significantly better than that of those in the control group within 3 months after treatment. CONCLUSION: Intensified antithrombotic therapy followed by stenting can effectively reduce the risk of perioperative complications in CAS patients with highly severe stenosis accompanied by thrombosis and improve the long-term clinical prognosis of patients without increasing the risk of bleeding.

CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum.

Joubert syndrome (JS) is a recessive ciliopathy in which all affected individuals have congenital cerebellar vermis hypoplasia. Here, we report that CEP120, a JS-associated protein involved in centriole biogenesis and cilia assembly, regulates timely neuronal differentiation and the departure of granule neuron progenitors (GNPs) from their germinal zone during cerebellar development. Our results show that depletion of Cep120 perturbs GNP cell cycle progression, resulting in a delay of cell cycle exit in vivo. To dissect the potential mechanism, we investigated the association between CEP120 interactome and the JS database and identified KIAA0753 (a JS-associated protein) as a CEP120-interacting protein. Surprisingly, we found that CEP120 recruits KIAA0753 to centrioles, and that loss of this interaction induces accumulation of GNPs in the germinal zone and impairs neuronal differentiation. Importantly, the replenishment of wild-type CEP120 rescues the above defects, whereas expression of JS-associated CEP120 mutants, which hinder KIAA0753 recruitment, does not. Together, our data reveal a close interplay between CEP120 and KIAA0753 for the germinal zone exit and timely neuronal differentiation of GNPs during cerebellar development, and mutations in CEP120 and KIAA0753 may participate in the heterotopia and cerebellar hypoplasia observed in JS patients.

Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway.

BACKGROUND: The role of macrophages in rheumatoid arthritis (RA) and its mechanism have attracted much attention in RA pathogenesis. Macrophages accumulate in the synoviums of RA, and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages, leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction, which has made macrophages a potential target of RA drugs. Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity. It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio. AIM: To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA. METHODS: Elderly patients with RA and joint effusion were selected, including 10 men and 25 women, with an average age of 66.37 ± 4.42 years. Patients were treated with oral administration of 25 mg Iguratimod (Iremod, State Food and Drug Administration Approval No. H20110084) twice daily for 12 wk. Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment. Venous blood and joint effusion fluid were collected, mononuclear macrophages were extracted and expression of cell surface markers CD86, CD64, CD163, and CD206 was analyzed by flow cytometry. The concentration of inflammatory factors interleukin (IL)-6, IL-1ß, transforming growth factor-ß, and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay. Expression of mononuclear cells inhibitor of nuclear factor-κB (IκB) and phosphorylated IκB in peripheral blood was analyzed by western blotting. RESULTS: Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly. The percentage of cell surface markers CD86 and CD64 decreased significantly, and the percentage of CD163 and CD206 increased significantly (P < 0.05). The inflammatory factors IL-6 and IL-1ß decreased significantly, and transforming growth factor-ß and IL-4 increased significantly. Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment, and its phosphorylation level was significantly decreased (P < 0.05). CONCLUSION: Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway, thus improving symptoms of RA.

[High-dose immunosuppression and autologous peripheral blood stem cell transplantation for immunological reconstitution in two patients with primary Sjögren's syndrome].

OBJECTIVES: To assess the safety and efficacy of high-dose immunosuppression and autologous peripheral blood cell transplantation (APBSCT) in severe and refractory primary Sjögren's syndrome (pSS) and to analyze immune reconstitution in pSS. METHODS: Two patients with severe and refractory primary pSS were included in this study. They suffered still with active pSS despite the use of prednisone and immunosuppression agents. A regimen of high-dose immunosuppression and APBSCT was carried out for them. Dynamic T cell subgroup was tested with flow cytometry before and after PBSCT and the diversity of T cell receptor repertoire and CDR3 spectrum with RT-PCR and genescan. RESULTS: Both of the pSS cases underwent PBSCT smoothly. Clinical assessments showed improvement. Immune reconstruction lagged behind hematopoietic reconstitution. The skew of T cell receptor repertoire was somewhat corrected and CDR3 spectrum changed from oligoclonality to poly-clonality. CONCLUSION: High dose chemotherapy (HDC) and APBSCT are feasible and safe and can result in short-term or middle-term improvement of disease in patients with severe pSS which is refractory to conventional treatment. It is observed in this study that immune reconstruction recovered 3 moths after the treatment. Long-term efficacy of HDC + PBSCT in pSS should be studied in large number of cases with follow up of longer time.