Internal carotid artery stenosis: hemodynamics in the ipsilateral ACA affects CT angiography manifestations.

Objective: This study aimed to evaluate whether CT angiography (CTA) manifestations in anterior cerebral artery a1 segment (A1) were related to the hemodynamics in patients with internal carotid artery stenosis (ICAS). Methods: A total of 97 cases were selected. The degree of ICAS and symmetry of A1 were evaluated by CTA examination. Hemodynamic indexes were detected by transcranial Doppler (TCD). The differences in CTA presentations of A1 and hemodynamics between the vessels on the stenotic and contralateral sides were analyzed according to the different degrees of stenosis. The degree of ICAS according to the different manifestations of A1 and the hemodynamics of A1's adjacent vessels were also analyzed. Results: In the case of unilateral ICAS, the difference in Vm of A1 between the stenotic and the contralateral side was the most significant relative to the stenosis degree. When unilateral ICAS was ≥70%, the presentation of A1 on the stenotic side was more slender or non-visualized compared to that on the contralateral side, while in cases with unilateral stenosis <70% or bilateral stenosis with a similar degree of stenosis, A1 were mainly symmetrical. When A1 on the side of ICAS was slender or non-visualized, the Vm of A1 was significantly slower than that on the contralateral side (P < 0.001). Conclusion: The CTA manifestations of A1 on the side of ICAS embodied the overall changes of the intracranial hemodynamics after ICAS. A combination of TCD and CTA examination of A1 can assist in judging the location and degree of ICAS.

Generation and characterization of QLS22001, a humanized monoclonal antibody that neutralizes IL-17A and IL-17F with an extended half-life.

Therapeutic intervention to block IL-17A signaling has proven to be an effective treatment for numerous autoimmune diseases, including psoriasis, psoriatic arthritis, and axial spondylarthritis. Among the IL-17 family members, IL-17F, which shares 55% sequence homology with IL-17A, has been reported to functionally overlap with IL-17A in many inflammatory diseases. In this study, we describe the generation and characterization of QLS22001, a humanized monoclonal IgG1 antibody with an extended half-life and high affinity for both IL-17A and IL-17F. QLS22001 effectively blocks IL-17A and IL-17F mediated signaling pathways both in vitro and in vivo. Briefly, the YTE (M225Y/S254T/T256E) modification was introduced into the Fc fragment of QLS22001 WT Fc to prolong its half-life, and the resulting construct was named QLS22001. Functionally, it significantly inhibits IL-17A- and IL-17F-stimulated signaling in cell-based IL-6 release and reporter assays. The dual neutralization of the endogenous IL-17A and IL-17F produced by Th17 cells, as opposed to the selective blockade of IL-17A alone, results in a greater suppression of inflammatory cytokine secretion, according to in vitro blockade assays. Furthermore, in an in vivo mouse pharmacodynamic study, QLS22001 blocked human IL-17A-induced mouse keratinocyte chemoattractant (KC) release. In cynomolgus monkey pharmacokinetics evaluation, QLS22001 showed linear pharmacokinetic characteristics with a mean half-life of 31.2 days, while its parent antibody, QLS22001 WT Fc, had a mean half-life of 17.2 days. In addition, QLS22001 does not induce cytokine release in a human whole-blood assay. Collectively, these data provide a comprehensive preclinical characterization of QLS22001 and support its clinical development.

Improvements in Nerve Dissection Surgery Methodology for Spasmodic Torticollis Treatment.

Spasmodic torticollis is the most common focal dystonia and is characterized by aberrant involuntary contraction of muscles of the neck and shoulders, which greatly affects patients' quality of life. Consequently, patients with this condition often desire treatment to alleviate their symptoms. The common clinical treatments for spasmodic torticollis include interventions such as drug therapy, botulinum toxin injections, and surgery. Surgical treatment is feasible for patients who do not respond well to other treatments or who are resistant to drugs. The gradual improvement of surgeons' understanding of anatomy and the ongoing developments in surgical techniques since their advent in the 1640s have resulted in many innovative surgical approaches that have led to improvements in the treatment of spasmodic torticollis. Previously used surgical treatments that result in uncertain outcomes, various postoperative complications, and serious damage to motor functions of the head and neck have gradually been discontinued. Nerve dissection surgery is the most common surgical treatment for spasmodic torticollis. This article reviews existing research on nerve dissection surgery for the treatment of spasmodic torticollis and the history of its development, along with the advantages and disadvantages of various surgical improvements. This article aims to provide clinicians with practical advice.

UHPLC-MS/MS method for pharmacokinetic and bioavailability determination of five bioactive components in raw and various processed products of Polygala tenuifolia in rat plasma.

CONTEXT: Sibiricose A5 (A5), sibiricose A6 (A6), 3,6'-disinapoyl sucrose (DSS), tenuifoliside A (TFSA) and 3,4,5-trimethoxycinnamic acid (TMCA) are the main active components of Polygala tenuifolia Willd. (Polygalaceae) (PT) that are active against Alzheimer's disease. OBJECTIVE: To compare the pharmacokinetics and bioavailability of five active components in the roots of raw PT (RPT), liquorice-boiled PT (LPT) and honey-stir-baked PT (HPT). MATERIALS AND METHODS: The median lethal dose (LD50) was evaluated through acute toxicity test. The pharmacokinetics of five components after oral administration of extracts of RPT, LPT, HPT (all equivalent to 1.9 g/kg of RPT extract for one dose) and 0.5% CMC-Na solution (control group) were investigated, respectively, in Sprague-Dawley rats (four groups, n = 6) using UHPLC-MS/MS. In addition, the absolute bioavailability of A5, A6, DSS, TFSA and TMCA after oral administration (7.40, 11.60, 16.00, 50.00 and 3.11 mg/kg, respectively) and intravenous injection (1/10 of the corresponding oral dose) in rats (n = 6) was studied. RESULTS: The LD50 of RPT, LPT and HPT was 7.79, 14.55 and 15.99 g/kg, respectively. AUC 0- t of RPT, LPT and HPT were as follows: A5 (433.18 ± 65.48, 680.40 ± 89.21, 552.02 ± 31.10 ng h/mL), A6 (314.55 ± 62.73, 545.76 ± 123.16, 570.06 ± 178.93 ng h/mL) and DSS (100.30 ± 62.44, 232.00 ± 66.08, 197.58 ± 57.37 ng h/mL). The absolute bioavailability of A5, A6, DSS, TFSA and TMCA was 3.25, 2.95, 2.36, 1.17 and 42.91%, respectively. DISCUSSION AND CONCLUSIONS: The pharmacokinetic and bioavailability parameters of each compound can facilitate future clinical studies.

UHPLC-MS/MS method for simultaneous determination of Radix Polygalae glycolipids and organic acids in rat plasma and application in a pharmacokinetic study.

Radix Polygala (Yuanzhi in Chinese) is well-known in traditional Chinese medicine (TCM) and has been used for treatment of depression, brain protection, and memory improvement for thousands of years. This plant medicine is rich in saponins, glycolipids, and organic acids. The purpose of the current study was to develop a rapid, accurate, and sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the following seven active components of Radix Polygala extracts in rat plasma: sibiricose A5 (A5); sibiricose A6 (A6); 3,6'-disinapoyl sucrose (DSS); tenuifoliside A (TFSA); tenuifoliside B (TFSB); tenuifoliside C (TFSC); and 3,4,5-trimethoxycinnamic acid (TMCA). Then, the pharmacokinetics were studied following oral administration. Plasma samples were precipitated with methanol. Chromatographic separation was successfully performed on a thermo C18 column (100 × 3.0 mm, 3 µm) with a mobile phase consisting of acetonitrile and 10 mmol/L of an ammonium acetate aqueous solution. Seven analytes were detected by multiple reaction monitoring (MRM) with an electrospray ionization source in the positive mode. The transitions of m/z were 517.1/174.9, 547.0/204.9, 753.2/205.2, 681.3/443.3, 667.2/205.1, 767.4/529.2, 236.8/103.2, and 136.9/92.9 for A5, A6, DSS, TFSA, TFSB, TFSC, TMCA, and salicylic acid (IS), respectively. The method validation showed good linearity in the range of 1-2000 ng/mL and LLOQs of 1 ng/mL for the 7 components in plasma. The accuracy, precision, and stability of QC samples were all within allowable ranges. In addition, no significant matrix effect was observed using this method. For the first time, the validated method has been successfully applied to the pharmacokinetic study of the seven components of Radix Polygala extracts in rat plasma. Moreover, this method may be applied for detecting prescriptions that contain Radix Polygala or other plant medicines that include one or more components above. The results of the pharmacokinetic study of the seven ingredients will provide important guidance to clinical medicine regarding Radix Polygala and prescriptions include Radix Polygala.

Fingerprint and multi-ingredient quantitative analyses for quality evaluation of hawthorn leaves and Guang hawthorn leaves by UPLC-MS

ABSTRACT This paper aimed to evaluate the quality of hawthorn leaves and Guang hawthorn leaves by an UPLC-MS method from two aspects, fingerprint analysis and multi-ingredient quantification. Chromatographic separation was carried out on an UPLC system, the standardized characteristic fingerprints was established by Similarity Evaluation System for chromatographic fingerprinting of traditional Chinese medicine and cluster analysis. Eight components were simultaneously determined by mass spectrometry in multiple reaction-monitoring mode. The method was validated in terms of linearity (R2 > 0.9971), intraday and interday precision (RSD < 2.0%), repeatability (RSD < 2.3%), stability (RSD < 2.5%) and recovery (96.2-103.8%). The developed method was successfully applied to the quality evaluation between hawthorn leaves and Guang hawthorn leaves, and there were differences in the component and the content, hawthorn leaves and Guang hawthorn leaves cannot substitute each other in clinical medication.