Publications by authors named "Q-Z Yang"
Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.
View Article and Find Full Text PDFConsensus on the lung cancer management after third-generation EGFR-TKI resistance.
Lancet Reg Health West Pac
December 2024
Article Synopsis
- Lung cancer is the most common type of cancer in the Asia-Pacific region, with non-small cell lung cancer (NSCLC) making up about 85% of cases, and a significant mutation rate of 40-60% in Asian patients with lung adenocarcinoma.
- Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) have improved treatment for NSCLC with mutations, but managing resistance to these drugs is still a major issue with no standardized guidelines.
- A set of recommendations has been developed, integrating international guidelines and regional clinical experiences, to help healthcare providers classify resistance, conduct clinical testing, and devise treatment strategies for patients struggling with resistance to third-generation EGFR-TKIs.
Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.
Methods: Patients with ischemic stroke presenting 4.
DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.
View Article and Find Full Text PDFBackground: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.
Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.
Background: In the traditional computed tomography (CT) simulation process, patients need to undergo CT scans before and after injection of iodine-based contrast agent, resulting in a cumbersome workflow and additional imaging dose. Contrast-enhanced spectral CT can synthesize true contrast-enhanced (TCE) images and virtual noncontrast (VNC) images in a single scan without geometric misalignment. To improve work efficiency and reduce patients' imaging dose, we studied the feasibility of using VNC images for radiotherapy treatment planning, with true noncontrast (TNC) images as references and explored its dosimetric advantages compared to using TCE images.
View Article and Find Full Text PDFArticle Synopsis
- The study aimed to evaluate how tourniquet usage impacts surgical time, muscle injury, and pain after ACL reconstruction.
- Researchers conducted a systematic review of randomized controlled trials, extracting data on various factors such as operative time and postoperative pain across seven studies with 471 participants.
- Findings indicated that tourniquet use reduced surgery duration but was linked to increased muscle injury markers (higher CPK levels) and greater postoperative pain and blood loss.
Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.
Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.
Article Synopsis
- A study was conducted to find out the best systolic blood pressure targets for patients over 50 with type 2 diabetes and high cardiovascular risk, comparing intensive treatment (target <120 mm Hg) to standard treatment (target <140 mm Hg) over 5 years.
- Out of 12,821 patients, the intensive treatment group had a lower average systolic blood pressure after one year (121.6 mm Hg) compared to the standard group (133.2 mm Hg), resulting in significantly fewer major cardiovascular events.
- Despite the lower overall events in the intensive group, there were more cases of symptomatic hypotension and hyperkalemia, but the rates of serious adverse events were similar in both groups.
Background: We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy.
Methods: We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery.
Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.
View Article and Find Full Text PDFPurpose To explore the role of cardiac MRI feature tracking (FT) and T1 mapping in predicting sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and to investigate their possible incremental value beyond ARVC risk score. Materials and Methods The retrospective study analyzed 91 patients with ARVC (median age, 36 years [IQR, 27-50 years]; 60 male, 31 female) who underwent cardiac MRI examinations between November 2010 and March 2022. The primary end point was the first occurrence of sustained VA after cardiac MRI to first VA, with censoring of patients who were alive without VA at last follow-up.
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- Zorifertinib is an experimental cancer drug that targets mutations in the EGFR gene and has shown effectiveness in patients with lung cancer that has spread to the brain.
- A phase 3 trial compared zorifertinib to standard treatments and found that it significantly extended the time patients lived without the disease worsening (progression-free survival).
- Results indicate that zorifertinib may be a better first-line treatment option for non-small cell lung cancer due to its ability to improve survival and manage side effects effectively.
Article Synopsis
- - Recent advancements in synthesizing organofluorine compounds have primarily focused on traditional methods, but this study introduces a novel enzymatic approach using iron-catalyzed radical transfer for creating C-F bonds.
- - The researchers repurposed an enzyme called HppE to effectively catalyze a specific type of fluorination to produce chiral benzylic fluoride products, achieving high efficiency and selectivity.
- - The study's findings suggest that the rate-determining step is related to activating the N-F bond, and the effectiveness of the process increases with the presence of sodium azide, improving the reaction's spatial dynamics.
Purpose: To investigate the effectiveness and maintenance of perceptional learning (PL) on vision improvement in keratoconus (KC) patients corrected with spectacles.
Design: Randomized, double-blind clinical trial.
Methods: Non-progressive KC patients 9 years of age or older who had best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.
Article Synopsis
- * Pulmonary long COVID was observed in 8.7% and 17.8% of patients at 1- and 2-year visits, while renal long COVID affected 15.2% and 23.9% of patients, respectively.
- * A machine learning model accurately predicted these long COVID outcomes using initial clinical and multi-omics data, and proteomics identified specific biomarkers linked to lung and kidney issues.
All-RNA-mediated targeted gene integration methods, rendering reduced immunogenicity, effective deliverability with non-viral vehicles, and a low risk of random mutagenesis, are urgently needed for next-generation gene addition technologies. Naturally occurring R2 retrotransposons hold promise in this context due to their site-specific integration profile. Here, we systematically analyzed the biodiversity of R2 elements and screened several R2 orthologs capable of full-length gene insertion in mammalian cells.
View Article and Find Full Text PDFUltrasound Characteristics Can Predict Response to Biologics Therapy in Stricturing Crohn's Disease.
Clin Transl Gastroenterol
August 2024
Article Synopsis
- Stricture, a common issue in Crohn's disease, can hinder effective treatment, making it crucial to identify which patients won't respond well to biologic therapy.
- This study analyzed ultrasound features of strictures in 43 patients, looking at factors like bowel wall thickness and creeping fat, to determine their association with treatment outcomes over at least a year.
- Findings indicated that specific ultrasound characteristics, especially a creeping fat wrapping angle greater than 180°, could predict the need for surgery and the likelihood of achieving steroid-free clinical remission in these patients.
Background: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown.
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- Nonsurgical treatments like the levonorgestrel intrauterine device (LIUD) are being explored for managing endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC), highlighting a need for long-term efficacy data.
- In a study of 43 patients initially responding to LIUD, 39% relapsed, with significant factors for shorter duration of response including younger age and lack of response at the 6-month mark.
- Molecular analysis during the study revealed changes in immune cell populations and pathways involved in relapse, suggesting immune mechanisms play a crucial role in the treatment's effectiveness.
Article Synopsis
- A phase 2 trial tested neoadjuvant SHR-1701, with or without chemotherapy, in patients with unresectable stage III non-small-cell lung cancer (NSCLC), showing promising results.
- The treatment achieved a post-induction objective response rate of 58% and an 18-month event-free survival rate of 56.6%, with surgical patients showing even better outcomes.
- Overall, 25% of patients underwent successful surgery, indicating that neoadjuvant therapy could enable surgical intervention for patients who initially had unresectable tumors.
Article Synopsis
- The study evaluates the effectiveness of neoadjuvant immunotherapy combined with chemotherapy in patients with localized EGFR-mutant non-small cell lung cancer (NSCLC) through a phase 2 trial involving 18 participants.
- Interim results show that while many patients had positive radiological responses, only 44% reached major pathological response, and there were no cases of complete response.
- The research indicates that certain T cell populations are linked to resistance against immunotherapy and suggests that monitoring circulating tumor DNA (ctDNA) could help identify patients less likely to respond to such treatments.
Background And Objectives: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes.
Methods: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China.
Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.
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