Rapid spread of mannan to the immune system,skin and joints within 6 hours after local exposure

Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic, because at least some of them induce Ps-, PsA- and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in-vivo transport and spread of mannan labelled with fluorine-18 [¹⁸F]. The results showed that mannan was transported to joints (knee) and bone marrow (tibia) of mice within 6 h after intraperitoneal injection. The time it took to transport mannan, and its presence in blood, indicated cellular transport of mannan within the circulatory system. In addition, mannan was filtered mainly through the spleen and liver. [¹⁸F]fluoromannan was excreted via kidneys, small intestine and, to some extent, the mouth. In conclusion, mannan reaches joints rapidly after injection, which may explain why mannan-induced inflammatory disease is targeted to these tissues.     

Bands of Fontana are caused exclusively by the sinusoidal path of axons in peripheral nerves and predict axon path; evidence from rodent nerves and physical models

The precise cause of the bands of Fontana, striations on peripheral nerves visible to the naked eye, has been the subject of debate for hundreds of years. Some researchers have described them as reflecting the sinuous course of nerve fibres passing through nerves, and others have proposed that endoneurial collagen and sheaths surrounding nerves play a role in their appearance. We hypothesised that the bands are caused exclusively by reflection of light from the surfaces of nerve fibres travelling in phase in sinusoidal waveforms through peripheral nerves. We aligned images of obliquely illuminated nerves with confocal images of axons in those nerves, and the numbers and positions of the bands precisely matched the axonal waves. We also developed three‐dimensional models of nerves with representations of the sinusoidal path of axons at their surface. We observed patterns resembling the bands of Fontana when these models were obliquely illuminated. This provides evidence that the bands of Fontana can be caused by light reflected sinusoidal path of axons alone. We subsequently describe a mechanism of band production based on our observations of both nerves and models. We report that smaller diameter nerves such as phrenic nerves and distal branches of sciatic nerves have shorter band intervals than larger nerves, such as proximal trunks of sciatic nerves, and that shorter band intervals correlate with longer axons per unit length of nerve, which suggests a greater tolerance to stretch. Inspection of banding patterns on peripheral nerves may permit prediction of axon length within nerves, and assist in the interpretation of nerve conduction data, especially in diseases where axon path has become altered.     

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter,randomized, open-label,phase 2 trial

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).     

Tumor Mutation Burden,Immune Cell Infiltration,and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors.Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model.Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis.Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635.Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.     

Increased intracranial hemorrhage of mechanical thrombectomy in acute ischemic stroke patients with atrial fibrillation

Journal of Thrombosis and Thrombolysis - The impact of atrial fibrillation (AF) on outcomes of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is controversial, and with a paucity of...     

枕下三角的超声解剖学研究

目的探讨枕下三角境界及内容物的检查方法与超声解剖学特点,为临床检查枕下三角提供超声影像学资料。方法对100例健康成年人枕下区进行超声检查,描述枕下三角境界的超声判定及解剖关系;阐述枕大神经的走行特点,测量头下斜肌表面枕大神经的横截面积;记录椎动脉V3段管腔内径(D)、收缩期峰值流速(PSV)、舒张期末流速(EDV)、阻力指数(PI)。结果 (1)寰椎后结节左侧约1 cm处纵切声像图显示寰椎后弓呈"短弧形"强回声,其后上方为头后大直肌、后下方为头下斜肌,三者分别构成枕下三角的底、内上界和外下界。(2)寰椎侧块处纵切声像图显示侧块为"平台样"强回声结构,其后方为椎动脉V3段、下方紧接寰椎后弓;后弓后方为头下斜肌、后上方为头上斜肌,头上斜肌构成三角的外上界,后弓与椎动脉V3段之间为枕下神经所在区域。(3)枕大神经长轴声像图显示神经从头下斜肌下缘发出后向内上走行于头下斜肌及头后大直肌与头半棘肌之间;不同性别头下斜肌表面枕大神经横截面积两侧比较,差异均无统计学意义(P>0.05)。(4)寰椎侧块处横切声像图显示椎动脉V3段呈"倒U形"绕侧块进入枕骨大孔,排除发育不良者,测V3段D为(3.52±0.39)mm、PSV及EDV分别为(43.33±9.05)、(21.87±5.86)cm/s、RI为(0.49±0.11)。结论超声是检查枕下三角及其内容物的理想方法。