OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective: To explore a simple, effective, and safe method for excluding false positives and identifying infections by comprehensively evaluating blood donors with reactive HIV screening results, thereby providing a basis for developing management strategies for such donors. Methods: HIV testing data of blood donors from our laboratory from January 2022 to December 2024 were collected. The results of ELISA and nucleic acid testing (NAT) were combined with confirmatory results from the CDC and analyzed. Results: A total of 605 929 samples were tested for HIV over the three-year period, with 682 reactive samples (reactive rate: 11.25 per 10 000). All were sent to the CDC for Western blot (WB) confirmation, resulting in 53 confirmed positives ((confirmed positive rate: 7.77%). Among these, 619 samples showed isolated HIV Ag&Ab reactivity with non-reactive NAT (HIV Ag&Ab+-&HIV RNA or NAT NR), with a confirmed infection rate of 0%; 9 samples showed dual HIV Ag&Ab reactivity with non-reactive NAT (HIV Ag&Ab++&HIV RNA NR or NAT NR), also with 0% confirmed infection; 52 samples showed dual HIV Ag&Ab reactivity and reactive NAT (HIV Ag&Ab++&HIV RNA R or NAT R), all confirmed as positive (100% infection rate); and 2 HIV Ag&Ab dual-reactive samples without NAT detection were also confirmed infected (100%). For all four HIV Ag&Ab assays, the S/CO values in the true positive group with dual reactivity were significantly higher than those in the false-positive groups (P<0.05). The S/CO distributions for both single-reactive false positives and dual-reactive false positives were narrow, with the upper box (Q3, 75th percentile) below optimal cutoff values in all cases (The optimal cutoff values for the four reagents were 5.00, 11.67, 8.50, and 20.90, respectively). Conclusion: Blood donors with positive NAT results in HIV blood screening are permanently deferred. Donors with dual positive HIV Ag&Ab but negative NAT results are classified and managed based on the S/CO values of HIV Ag&Ab and the optimal screening thresholds. Donors with single positive HIV Ag&Ab but negative NAT results are placed under evaluation status and retain their eligibility to donate blood. Optimizing the management measures for blood donors and establishing a scientific stratified management and assessment mechanism can effectively maintain the stability of the blood donor team.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: Renal allograft rejection, either acute or chronic, is prevalent among many recipients. This study aimed to identify multiple Doppler ultrasound parameters for predicting renal allograft rejection. Materials and Methods: Between November 2021 and April 2022, 61 renal allograft recipients were studied prospectively after excluding two patients with dual transplants and seven with hydronephrosis. The analysis excluded 11 cases (10 due to missing Doppler data or pathology reports and one due to a high interquartile range/median dispersion value), resulting in a final analysis of 50 patients. Clinical characteristics, color Doppler imaging, superb microvascular imaging, and shear-wave imaging parameters were assessed by three experienced genitourinary radiologists. The Banff classification of the biopsy tissue served as the reference standard. Univariable and multivariable logistic regression, contingency matrices, and multiple machine-learning models were employed to estimate the associations. Results: Fifty kidney transplant recipients (mean age, 53.26±8.86 years; 29 men) were evaluated. Elasticity (≤14.8 kPa) demonstrated significant associations for predicting the combination of (borderline) T cell-mediated rejection (TCMR) categories (Banff categories 3 and 4) (p=0.006) and yielded equal or higher area under the receiver operating characteristics curve (AUC) values compared to various classifiers. Dispersion (>15.0 m/s/kHz) was the only significant factor for predicting the combination of nonTCMR categories (Banff categories 2, 5, and 6) (p=0.026) and showed equal or higher AUC values than multiple machine learning classifiers. Conclusion Elasticity (≤14.8 kPa) showed a significant association with the combination of (borderline) TCMR categories, whereas dispersion (>15.0 m/s/kHz) was significantly associated with the combination of non-TCMR categories in renal allografts.

Objective: This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance. Methods: We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations. Results: A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes. Conclusion Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.

Background and Objectives: Obstructive sleep apnea (OSA) has been associated with an increased risk of cancer in various organs. OSA is also linked to chronic inflammation in the biliary tract and pancreas, a well-established risk factor for carcinogenesis in these organs. However, its relationship with biliary tract and pancreatic cancers remains unclear and has been rarely investigated. Therefore, we aimed to evaluate whether OSA serves as an independent risk factor for these malignancies by analyzing a nationwide healthcare claims database in South Korea. Methods: A retrospective cohort study was conducted using the Korean National Health Insurance Service (KNHIS) database. Adults aged ≥20 years who were newly diagnosed with OSA (ICD-10: G47.30) between 2007 and 2014 were identified and propensity score-matched (1:5) with controls based on age, sex, and comorbidities. Individuals with pre-existing cancer diagnoses were excluded. The primary endpoints were the incidence of overall cancer, biliary tract cancer (C23–C24), and pancreatic cancer (C25). Cox proportional hazards regression models were used to calculate hazard ratios (HRs), adjusting for demographic and clinical factors. Results: A total of 1,191,444 individuals were included, comprising 198,574 patients diagnosed with OSA and 992,870 matched controls. OSA was associated with an increased overall cancer incidence (HR, 1.132; 95% confidence interval [CI], 1.097–1.169); however, it was not significantly associated with pancreatic cancer (HR, 0.941; 95% CI, 0.823–1.072) or biliary tract cancer (HR, 0.931; 95% CI, 0.751–1.142). Subgroup analyses stratified by sex and age revealed no statistically significant associations across these groups. Conclusion Our findings do not support OSA as an independent risk factor for biliary tract or pancreatic cancers.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.