眶隔后壁-上睑提肌复合体折叠法矫正轻度上睑下垂的临床疗效分析

目的探讨眶隔后壁-上睑提肌复合体折叠法矫正轻度上睑下垂的效果。方法回顾性分析北京大学深圳医院2018年1月至2020年1月收治的轻度上睑下垂患者的临床资料,均由同一术者应用眶隔后壁-上睑提肌复合体折叠法进行治疗,记录术后并发症;术后6个月评估双眼对称性,包括优、良好、差;术后12个月评价上睑下垂矫正效果,包括矫正良好、基本矫正、矫正欠佳、矫正过度。结果共纳入85例患者,男36例,女49例,年龄(25.0±4.1)岁,其中双侧62例,单侧23例。获随访12个月。术后所有患者无血肿、感染、暴露性角膜炎、穹隆结膜脱垂等并发症发生。85例中双眼对称性达优者63例,良好17例,差5例,优良率为94.1%(80/85)。上睑下垂矫正良好72例,基本矫正9例,矫正欠佳4例,手术有效率为95.3%(81/85)。结论应用眶隔后壁-上睑提肌复合体折叠法矫正轻度上睑下垂,操作简单、易掌握,损伤较小,安全而有效。     

Subcutaneous administration of botulinum toxin A reduces formalin-induced pain

Botulinum toxin type A (BoNT-A) produced by the bacterium Clostridium botulinum is a potent inhibitor of acetylcholine release in the neuromuscular junction and has been used to treat many disorders related to excessive muscle contraction. However, BoNT-A has recently been used in pain therapy to treat myofascial pain, low back pain and various types of headaches, including migraine. The purpose of this study is to investigate the antinociceptive effect of BoNT-A and its underlying mechanism in the rat formalin inflammatory pain model. BoNT-A (3.5, 7, 15 and 30 U/kg) or vehicle was administered to the plantar surface of the right hindpaw of male Sprague-Dawley rats. BoNT-A dose-dependently (P<0.05) inhibited formalin-induced nociceptive behavior during phase 2 but not during phase 1 when administered 5 h to 12 days before formalin challenge. The onset of the antinociceptive effect started at 5 h after pre-treatment and this effect lasted for at least 12 days. BoNT-A (7 U/kg) also reduced edema. Consistent with the lack of effect in the formalin phase 1, BoNT-A, at 15 U/kg, had no effect on acute thermal nociception; no local muscle weakness was observed at this dose. Pre-treatment of rats with BoNT-A (3.5, 7 or 15 U/kg) all significantly reduced formalin-evoked glutamate (Glu) release. These results demonstrate that local peripheral injection of BoNT-A significantly reduces formalin-induced nociceptive behaviors with the absence of obvious muscle weakness. Such an antinociceptive effect of BoNT-A is associated with the inhibition of formalin-induced release of Glu (and/or neuropeptides) from primary afferent terminals.     

Formosanin C promotes the curative efficacy of ultrasound-guided radiofrequency ablation in a mouse model of breast cancer

Breast cancer is the leading cause of tumor-associated death among women worldwide, and new therapeutic strategies are required to improve the post-surgery prognosis and quality of life of patients. Radiofrequency ablation (RFA) is a less invasive approach compared with traditional surgical resection to treat malignancies, and the combination of RFA and chemotherapeutic agents, including formosanin C (FC), can synergistically improve the curative effects against breast carcinoma. However, the detailed mechanisms remain unclear. In the present study, nude mice were used to identify the influence of FC on the therapeutic efficacy of RFA for breast cancer. Flow cytometry was performed to demonstrate the proportional alteration of CD8⁺ and CD45⁺ T cells with different biomarkers, including CD107a, IFNγ and TNFα. It was demonstrated that FC enhanced the therapeutic efficacy of RFA in breast cancer, while RFA combined with FC improved the proportion of IFNγ⁺ and TNFα⁺ CD8⁺ T cells and CD107a⁺ CD8⁺ T cells in tumor-infiltrating lymphocytes, thus increasing the immune responses caused by surgery and chemotherapy. The present study indicated that FC may promote the curative efficacy of ultrasound-guided RFA against breast tumor by regulating adaptive immune responses.     

Anti-ovarian cancer potential of phytocompound and extract from South African medicinal plants and their role in the development of chemotherapeutic agents

Ovarian cancer (OC) accounts for the highest tumor-related mortality among the gynecologic malignancies. Most of the OC patients diagnosed with advanced-stage (III and IV) this situation creates panic and provokes an emergency to discover a new therapeutic strategy. Plants that possess medicinal properties are gaining attention as they are enriched with various chemical compounds that are potential to treat various diseases. It is a prolonged process to provide innovative and significant leads against a range of pharmacological targets for a human disease management system. Though challenges and difficulties are faced in the development of a new drug, the emergence of combinatorial chemistry is providing a new ray of hope and also, the executed effort in discovering the drug, and a chemical compound has been remarkably successful. This review discussed the role of medicinal plants that are native of South Africa in treating the Ovarian Cancer and in drug discovery.     

High expression of miR-195 is related to favorable prognosis in cytogenetically normal acute myeloid leukemia

Background

Acute myeloid leukemia (AML) is a heterogeneous blood disease with poor treatment effect and high recurrence rate. With the deepening of non-coding RNA research, more and more miRNAs have been found to participate in various physiological processes of tumors. In this study, we tried to find the miRNA related to the prognosis of AML.

Methods

Collect gene expression data and clinical information of AML patients in the Cancer Genome Atlas database for statistical analysis. The expression level of miR-195 of each patient was standardized by logCPM and then produced as a box plot according to subtype classification. TargetScan was used to predict the target genes of miR-195, and these genes were subjected to GO pathway enrichment analysis by Metascape. Differential miRNAs were screened through the DESeq2 package in the R language. Survival rates were estimated using the Kaplan–Meier method and the log-rank test. The multivariate Cox proportional hazard models of EFS and OS were established.

Results

We found that the expression of miR-195 was the lowest in cytogenetically normal (CN-) AML, and high expression of miR-195 only promoted the prognosis of chemotherapy-only CN-AML patients (EFS: P?=?0.016; OS: P?=?0.035). Multivariate analysis showed that miR-195^high was a favorable and independent factor for CN-AML (both P?<?0.05). Further analysis showed that miR-195 may affect signal transduction through ANHAK2 in AML.

Conclusion

We found that high expression of miR-195 can increase prognosis time of chemotherapy-only CN-AML patients, providing a new possibility for treatment.

     

Transesophageal Echocardiography of Intracardiac Thrombus in Congenital Heart Disease and Atrial Flutter: The Importance of Thorough Examination of the Fontan

Transesophageal echocardiography (TEE) is used in atrial flutter or fibrillation (AFF) before electric cardioversion to detect intracardiac thrombi. Previous studies have described the use of TEE to diagnose intracardiac thrombi in the left atrium and left atrial appendage, which has an incidence of 8 % among patients without congenital heart disease (CHD). In their practice the authors have noted a significant incidence of intracardiac thrombi in other structures of patients with CHD and AFF. This study aimed to determine the incidence and location of intracardiac thrombi using TEE in patients with CHD requiring electric cardioversion of AFF and to compare the use of TEE and transthoracic echo (TTE) to detect intracardiac thrombus in this population. A retrospective chart review of TEE and TTE findings for all patients with CHD who had electric cardioversion of AFF at our institution from 2005 to 2013 was conducted. The diagnosis, presence, and location of intracardiac thrombus were determined. The TEE and TTE results were compared. The study identified 27 patients with CHD who met the study entry criteria at our institution between 2005 and 2013. Seven of these patients had a single ventricle with Fontan palliation. All the patients presented with AFF and had TEE before electric cardioversion. No patients were excluded from the study. The patients ranged in age from 2 to 72 years (median, 21 years) and weighed 17–100 kg (median, 65 kg). The duration of AFF before TEE and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days). Intracardiac thrombus was present in 18 % (5/27) of the patients and in 57 % (4/7) of the Fontan patients with AFF. No embolic events were reported acutely or during a 6-month follow-up period. Among patients with CHD who present with AFF, a particularly high incidence of intracardiac thrombi is present in the Fontan patients that may be difficult to detect by TTE. Thorough TEE examination of the Fontan and related structures is indicated before electric cardioversion of AFF. The incidence of intracardiac thrombus in CHD patients is more than double that reported in non-CHD patients.     

Crystallization scale purification of α7 nicotinic acetylcholine receptor from mammalian cells using a BacMam expression system

Aim:

To report our methods for expression and purification of α7 nicotinic acetylcholine receptor (α7-nAChR), a ligand-gated pentameric ion channel and an important drug target.

Methods:

α7-nAChRs of 10 different species were cloned into an inducible BacMam vector with an N-terminal tag of a tandem maltose-binding protein (MBP) and a TEV cleavage site. This α7-nAChR fusion receptor was expressed in mammalian HEK293F cells and detected by Western blot. The expression was scaled up to liters. The receptor was purified using amylose resin and size-exclusion chromatography. The quality of the purified receptor was assessed using SDS-PAGE gels, thermal stability analysis, and negative stain electron microscopy (EM). The expression construct was optimized through terminal truncations and site-directed mutagenesis.

Results:

Expression screening revealed that α7-nAChR from Taeniopygia guttata had the highest expression levels. The fusion receptor was expressed mostly on the cell surface, and it could be efficiently purified using one-step amylose affinity chromatography. One to two milligrams of the optimized α7-nAChR expression construct were purified from one liter of cell culture. The purified α7-nAChR samples displayed high thermal stability with a Tm of 60 °C, which was further enhanced by antagonist binding but decreased in the presence of agonist. EM analysis revealed ring-like structures with a central hydrophilic hole, which was consistent with the pentameric assembly of the α7-nAChR channel.

Conclusion:

We have established methods for crystallization scale expression and purification of α7-nAChR, which lays a foundation for high-resolution structural studies using X-ray crystallography or single particle cryo-EM analysis.