Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. For the controversy of anti-RAS drugs application, we also give theoretical analysis and discussed for drug application. These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies.

Objective To investigate the roles of high-resolution magnetic resonance imaging (HR-MRI) in the diagnosis and treatment of vertebrobasilar dissecting aneurysms (VBDA).Methods From January 2016 to December 2016,62 patients with VBDA admitted to Xuanwu Hospital,Capital Medical University using 3.0 T HR-MRI (3D-TOF-MRA,3D-T1WI,and 3D-T1WI+C sequence) and diagnosed by DSA were analyzed retrospectively.They were divided into either an asymptomatic group (n=18) or a symptomatic group (n=44) according to their medical histories.Their clinical features,imaging features,and the relationship with prognosis were analyzed.Results HR-MRI revealed that the double lumen sign/intimal flap accounted for 27.8% (n=5) and 54.5% (n=24) respectively in the asymptomatic group and symptomatic group.The intramural hematoma accounted for 22.2% (n=4) and 43.2% (n=19) respectively in both groups.The enhancement of aneurysmal wall accounted for 33.3% (n=6) and 77.3% (n=34) in the asymptomatic group and symptomatic group.There were significant differences in the above features between the two groups (all P<0.05).In the symptomatic group,18.2% (n=8) of patients had aneurysm recurrence,which was significantly higher than the asymptomatic group (5.6%,n=1).The difference between the two groups was statistically significant (P<0.05).Conclusions HR-MRI can better reveal the lesion characteristics of VBDA.The rates of aneurysmal wall enhancement and recurrence in symptomatic VBDAs are higher,which indicates that HR-MRI can assess the stability of the aneurysmal wall and identify the prognosis to a certain extent.

Objective To investigate the effect of state anxiety and trait anxiety on attentional orienting of heroin addicts. Methods State anxiety and trait anxiety was measured by State-Trait Anxiety Inventory (STAI). Forty heroin ad?dicts (36 males and 4 females) and 40 healthy controls (36 males and 4 females) participated in cue-target task. Atten?tional orienting and reorienting were measured in valid cue trials and invalid cue trails. Results Heroin addicts had sig?nificantly greater state anxiety [(42.65 ± 6.58) vs. (36.60 ± 8.91)] and trait anxiety [(44.43 ± 7.67) vs. (37.00 ± 8.63)] values than controls (P<0.05). The state anxiety was significantly correlated with orientation RT difference (r=-0.259, P=0.020) and disengaging/reorientation RT difference (r=0.333, P=0.003) in heroin addicts. Trait anxiety was also significantly cor?related with orientation RT difference (r=-0.248, P=0.026) and disengaging/reorientation RT difference (r=0.356, P=0.001) in heroin addicts. Conclusion Heroin addicts have significantly greater anxiety than healthy controls. Both their state anxiety and trait anxiety are associated with attentional orienting and disengaging/reorienting.

Objective To investigate the effect of endovascular treatment of vertebral basilar artery dissecting aneurysms. Methods The clinical data of 40 patients with vertebral basilar artery dissecting aneurysm admitted to Beijing Xuanwu Hospital and Haidian hospital,Capital Medical University from August 2013 to September 2014 were analyzed retrospectively. Their clinical symptoms and imaging were followed up. According to the treatment methods,they were divided into either a stent-assisted coil emboliza-tion group (group A;n = 34)or a parent artery occlusion (group B;n = 6),and according to the clinical symptoms and imaging followed-up,the efficacy was assessed at 1 year after procedure. Results The patients were followed up for 1 year after procedure,29 patients (85. 3%)were improved in group A, 1 (2.9%)was stable,and 4 (11. 8%)deteriorated. All the 4 deteriorated patients died of cerebral infarction complications (at 1 week to 6 months after procedure). The 6 patients in group B were improved compared with before procedure. No intracranial hemorrhage and ischemic events occurred. Conclusion Using the stent-assisted coil embolization technique and the parent artery occlusion technique for the treatment of the vertebral basilar artery dissecting aneurysms are relatively safe and effective.