Clinical challenges and research progress in variants of uncertain significance of inherited cardiovascular diseases

Ya-Ling Han, MD, PhD, was born in Wuhan, Hubei province, in 1953. She graduated from Haebin Medical University in 1978. She received her doctorate in 1994 from Shanghai Second Military Medical University. She was a visiting scholar at the National Heart Center, Singapore. She is currently a professor and the director of the Department of Cardiology, General Hospital of Shenyang Military Region; the director of the Cardiovascular Research Institute; and the director of the Key Laboratory of Acute Severe Cardiovascular Treatment Research of the Chinese People’s Liberation Army. She is the president of the Chinese College of Cardiovascular Physicians and Chairperson-elect of the Chinese Society of Cardiology. Dr Rutherford asks: Could you describe the scope of clinical cardiac care provided in the Department of Cardiology at the General Hospital of Shenyang Military Region? Dr Ya-L ing Han replies : The Department of Cardiology at the General Hospital of Shenyang Military Region, together with the departments of congenital heart disease and cardiovascular surgery, constitute the cardiovascular institute of the People’s Liberation Army, which is among the top 5 centers in China providing comprehensive care for CVD. Our center is located in Northeast China, an area with the highest prevalence of CAD, so the treatment and prevention of CAD is our major focus. We are a busy center: we perform ≈7000 PCIs, 1400 radiofrequency ablations, 550 pacemaker implantations, 900 congenital heart disease interventions, and ≈2500 cardiovascular surgeries annually, with an overall in-hospital mortality rate of <1%. We have pioneered many facets of CVD treatment in China, including PCI for complicated coronary lesions, CTO of coronary arteries, left main coronary disease, treatment of high-risk patients with AMI, novel antithrombotic strategies for coronary patients, and surgical and percutaneous treatment of complicated congenital heart disease. Over the past 2 decades, you and your team have …

Objective To establish a specialized division of labor system for cerebrovascular disease clinical research and verify the effectiveness of specialized division of labor system in the management of cerebrovascular disease clinical research. Methods Using Delphi method to establish the specialized division of labor system of clinical research, identify personnel responsibilities, access mechanism and access standards. Compare two clinical studies that using and not using this system in terms of clinical research management efficiency, effectiveness of the clinical research progress and quality control. Results Specialized division of labor system can reduce the time spent for research design and preparation, improve the research progress and data integrity, reduce the protocol deviation and the loss of subject follow up. Conclusions Specialized division of labor system can improve the efficiency of clinical research management and improve the research progress and quality. Key words: Specialized division of labor system; Clinical research; Effect evaluation

As potential alternatives to conventional antibiotics, antimicrobial peptides have attracted great attention in recent years. This review provides an overview of their characteristics and mechanisms of action, summarizes the current progress in clinical research and challenges in clinical utility. Antimicrobial peptides display robust activity against a wide variety of pathogens, including multidrug resistant bacteria, and are less susceptible to resistance development. Dozens of antimicrobial peptides are currently in various stages of clinical trials. However, some intrinsic drawbacks limit their clinical utility: toxicity, stability and manufacturing costs. Researchers have tried to modify the structure of antimicrobial peptides and worked on developing peptidomimetics. It is believed that antimicrobial peptides and peptidomimetics will play an important role against multidrug resistant bacteria in the future. Key words: Dermcidins; Infection; Drug resistance; Clinical Trial; Peptidomimetics

Chronic eczema is a common skin disease, which can occur in any part of the body, patients often consciously itch intensely, the skin appears to be local thickening, mossy changes and other manifestations, and is easy to recur, which seriously affects the patient's mental health and quality of life. Chinese medicine has a long history and rich experience in the treatment of chronic eczema. This paper summarises the progress of Chinese medicine clinical research in the treatment of chronic eczema, with a view to providing clinical reference.

The mission of the ANRS (the French National Agency for Research on AIDS and viral hepatitis) is to coordinate research, schedule appropriate events and meetings and fund projects on HIV and viral hepatitis. The Agency was created in 1988 to coordinate research on HIV/AIDS and as of 1 January 1999, the ANRS’ mission was expanded to include the task of coordinating and funding hepatitis C basic science and public health research. This role was expanded at the beginning of 2005 to all research on hepatitis B and C. Within a relatively limited time-frame, the ANRS was able to transfer its acquired HIV experience and adapt its reactivity and flexibility to the issues presented by hepatitis B and C clinical and public health research. As such, since 1999, the ANRS has funded 32 therapeutic trials, 31 physiopathological clinical research projects, four cohorts and over 300 basic research projects in the field of viral hepatitis. To reinforce research in the Middle East and Africa in 2007, the Agency created the ANRS site in Egypt, dedicated to clinical and basic research on hepatitis C genotype 4 (HCV-4). The ANRS-funded projects led by university or clinical researchers result in, on average, 500 peer-reviewed publications per year on both HIV and viral hepatitis research, half of which are published in journals with an impact factor >5. At an international level, a survey carried out by Inserm shows that France is ranked second for hepatitis research (9.3% of total publications). In 2011, the ANRS dedicated approximately 22% of its global budget to research in the domain of viral hepatitis. The ANRS funds research projects in all disciplines including basic research projects, pre-clinical, clinical studies and projects in social sciences. Moreover, the ANRS is currently funding a vaccine research programme for Hepatitis C, carried out at the Vaccine Research Institute (VRI) in partnership with Université Paris Est Créteil. In basic research, several aspects of hepatitis entry, assembly, replication and interaction with host cells are ANRS research priorities. In particular, the ANRS funds research in the following areas: The ANRS also supports a consortium of research groups devoted to the development and standardization of animal models, including humanized mouse models for studying viral hepatitis. In addition, in collaboration with Inserm and the Universities of Paris VI and XI, the ANRS has set up a genomic platform on the site of the Pitié-Salpetrière Hospital. The platform is set up for ultra-deep sequencing for genotype/phenotype association studies. The platform provides support for both hepatitis and HIV research. Despite notable progress in clinical research in the field of B and C viral hepatitis in recent years, a number of questions regarding patient care and the evolution of the disease remain unanswered. The ANRS therefore remains thoroughly involved in therapeutic trials, cohorts and physiopathology studies in the domain of viral hepatitis. The ANRS supervises a unique clinical network in the field of viral hepatitis research in France, comprising 28 clinical units. Moreover, the agency funds 23 staff positions for Clinical Research Associates. The current patient register for HBV-/HCV-infected individuals is over 69 000; 700 patients are included in clinical trials and 2700 in cohorts, not including HIV/hepatitis co-infected patients. The ANRS has strong ties with patient associations and community-based organisations, namely CHV (Collectif Hépatites Virales), which regroups several hepatitis organisations, including in particular SOS Hépatites. The associations provide advice on study protocols, in particular on trial information and patient consent sheets. In general terms, patient care needs to be improved, and patients with treatment-failure need to be able to access novel combinations of molecules. Inversely, patients with successful therapies could benefit from simplified or shorter drug regimens. Among our current priorities in clinical research on viral hepatitis are: Treatment options for chronically infected persons are at a paradigm shift. The two first-generation protease inhibitors, boceprevir and telaprevir, have been released in 2011 and are now to be used in the real-world. More than 70 new products directed against hepatitis B virus (HBV) and hepatitis C virus (HCV) are under clinical development. The ANRS has played a strong role in this therapeutic development by providing innovative support to the hepatitis community. Viral Hepatitis mono-infection The author has no disclosure.

Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with brain metastases

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC.

Glycated albumin and its variability: Clinical significance, research progress and overall review

Diagnosis of cracked tooth: Clinical status and research progress.

Patent Foramen Ovale (PFO), a common cardiac abnormality, has been established as the most prevalent cause of Cryptogenic Stroke (CS). In 2022, the American Society of Cardiovascular Angiography and Interventions (SCAI) officially defined PFO-induced CS as PFO-Associated Stroke (PFO-AS), whose onset characteristics and treatment methods are currently the focus of pertinent clinical research. Previously, the pathogenesis of PFO-AS was commonly believed to be related to Paradoxical Embolism (PDE) or in situ thrombosis. Recently, atrial heart disease, which could lead to abnormal cardiac structure and circulating biomarker accumulation, potentially causing vascular endothelial injury and promoting thrombosis, has also been associated with the pathogenesis of PFO-AS. Therefore, PFO-AS could be the outcome of multiple pathogenesis mechanisms. Furthermore, significant research progress has been made in elucidating the pathogenic PFO gene. Nonetheless, additional in-depth research is still required to better elucidate the precise mechanisms underlying PFO-AS. Notably, the clinical and imaging characteristics of PFO-related Ischemic Stroke (IS) are slightly different from those of other IS causes. Furthermore, the assessment of the correlation between PFO and stroke mostly relies on The Risk of Paradoxical Embolism Score (RoPE) and PFO-Associated Stroke Causal Likelihood classification (PASCAL) system, which could be a limitation. Additionally, PFO examinations mainly relied on cardiac anatomy evaluation in the past, highlighting another potential gap. Moreover, recent research suggests that PFO closure may increase the risk of Heart Failure (HF) with preserved Ejection Fraction (HFpEF). Conversely, after 2017, four Randomized Controlled Trials (RCTs): CLOSE, RESPECT, REDUCE, and DEFENSE-PFO, demonstrated that transcatheter PFO closure is more effective in preventing various risk events than conventional pharmacotherapy. This review comprehensively summarizes the latest research progress on PFO-AS pathogenesis, treatment, prevention, and management decisions, providing a valuable clinical reference.

Clinical research progress in bariatric and metabolism research had promoted the development in clinical practice. In U. S and Europe, pivotal scientific questions had been explored by clinical researchers, which brought the updating of guidelines, accumulation in key evidences, promotion of the consensus of metabolic benefits, following further development in scientific area. Compared to U. S and Europe, clinical practice in bariatric and metabolic surgery development in China started later. Clinical research in China just developed into initial phase with few achievements with high quality and breakthrough contribution. However, with wider practice, larger patient population and higher quality of surgery, clinical research in bariatric and metabolic surgery in China will go to a new stage through clinical research with standardized guidance, broad cooperation and clinical data digitalization and standardization.

To review current status of clinical application and research progress of different anticoagulants in perioperative period of free flap transplantation. A comprehensive review of recent relevant literature was conducted, focusing on clinical research concerning the application of anticoagulants in the perioperative period of free flap transplantation. The administration route, timing, dosage selection, effectiveness, and safety of commonly used and novel anticoagulants were summarized. At present, the anticoagulants mainly used in the perioperative period of free flap transplantation include drugs for venous thrombosis prophylaxis, drugs for arterial thrombosis prophylaxis, and physical/colloidal anticoagulants, etc. The administration strategies can be classified into two major categories: single-agent anticoagulation and combined anticoagulation. Single-agent anticoagulation mainly includes unfractionated heparin, low-molecular-weight heparin, aspirin, and novel anticoagulants. Combined anticoagulation is commonly a synergistic anticoagulation regimen dominated by heparin drugs, combined with aspirin, different antiplatelet drugs, and expansion agents. Studies indicate that perioperative anticoagulant administration can effectively reduce the risk of thrombosis in free flaps and improve the overall flap survival rate. However, significant differences exist in the impact of drug types, administration routes, initiation timing, and dosage intensity on efficacy and bleeding risk. A unified, standardized application protocol has not yet been established. In addition, there has been a growing number of studies on novel anticoagulant drugs. However, their superiority and optimal application strategies in the field of free flap transplantation still necessitate more high-quality evidence. Perioperative anticoagulation therapy represents one of the key strategies for improving the survival rate of free flaps. However, there is still a lack of high-level evidence to establish a standard protocol. Future research should focus on the optimization of individualized anticoagulation strategies, the validation of the effectiveness of new anticoagulants, and the exploration of the advantages of different anticoagulation strategies. At the same time, attention should be paid to balancing anticoagulation and bleeding risks to promote the standardization of clinical practice and the improvement of treatment safety.

Postoperative pain after spine surgery (POPSS) is a critical issue that affects patient recovery and quality of life, increasing the risk of complications such as thrombosis. The side effects of traditional pain management methods, such as intravenous opioid administration, limit their clinical application. Therefore, it has become essential to explore and investigate new pain management strategies. We conducted a review of the relevant literature on fascial plane blocks (FPBs) in postoperative pain management after spine surgery, sourced from CNKI and PubMed, with a search period from June 25, 2020, to April 20, 2025. Additionally, we manually examined the references of the included studies to identify any potentially overlooked literature. The review findings indicate that FPBs are a novel regional anesthesia technique and a key component of multimodal analgesia. With precise analgesic effects, ease of operation, high safety, and few complications, FPBs have become a research focus in postoperative pain management for spine surgery. This article provides a comprehensive review of the characteristics of postoperative spine pain, the anatomical basis of FPBs, clinical research progress, controversial studies and limitations, as well as future research directions, aiming to offer valuable references for both clinical practice and research.

Cardiovascular disease is the greatest threat to human life and health. The past decade has seen remarkable progress in clinical and basic cardiovascular research, and many areas of opportunity are promising. The pace of current progress in clinical and basic research is such that remarkable improvement in the quality and length of life for those at risk for cardiovascular disease is likely.

Simple SummaryIn recent years, chimeric antigen receptor (CAR)-T-cell therapy has achieved good results in hematological malignancies. Clinical trials on anti-MSLN CAR-T cells have shown that they have a high safety profile but limited efficacy. This article reviews the clinical research status, obstacles, progress and challenges of anti-MSLN CAR-T-cell therapy and summarizes the relevant strategies to improve the efficacy and safety of anti-MSLN CAR-T-cell therapy.Chimeric antigen receptor (CAR)-T-cell therapy is a kind of adoptive T-cell therapy (ACT) that has developed rapidly in recent years. Mesothelin (MSLN) is a tumor-associated antigen (TAA) that is highly expressed in various solid tumors and is an important target antigen for the development of new immunotherapies for solid tumors. This article reviews the clinical research status, obstacles, advancements and challenges of anti-MSLN CAR-T-cell therapy. Clinical trials on anti-MSLN CAR-T cells show that they have a high safety profile but limited efficacy. At present, local administration and introduction of new modifications are being used to enhance proliferation and persistence and to improve the efficacy and safety of anti-MSLN CAR-T cells. A number of clinical and basic studies have shown that the curative effect of combining this therapy with standard therapy is significantly better than that of monotherapy.