Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective To propose a classification method for ultrasound images of pedicle screw canals based on radiomics analysis,and to evaluate the integrity of the screw canal.Methods With thoracolumbar spine specimens from 4 fresh cadavers,50 pedicle screw canals were pre-established and ultrasound images of the canals were acquired.A total of 2 000 images(1 000 intact and 1 000 damaged canal samples)were selected.The dataset was randomly divided in a 4∶1 ratio using 5-fold cross-validation to form training and testing sets(consisting of 1 600 and 400 samples,respectively).Firstly,the optimal radius of the region of interest was identified using the Otsu's thresholding method,followed by feature extraction using pyradiomics.Principal component analysis and the least absolute shrinkage and selection operator algorithm were employed for dimensionality reduction and feature selection,respectively.Subsequently,3 machine learning models(support vector machine[SVM],logistic regression,and random forest)and 3 deep learning models(visual geometry group[VGG],ResNet,and Transformer)were used to classify the ultrasound images.The performance of each model was evaluated using accuracy.Results With a region of interest radius of 230 pixels,the SVM model achieved the highest classification accuracy of 96.25%.The accuracy of the VGG model was only 51.29%,while the accuracies of the logistic regression,random forest,ResNet,and Transformer models were 85.50%,80.75%,80.17%,and 75.18%,respectively.Conclusion For ultrasound images of pedicle screw canals,the machine learning model performs better than the deep learning model as a whole,and the SVM model has the best classification performance,which can be used to assist physicians in diagnosis.

Objective:To observe the effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in patients with knee osteoarthritis(KOA)due to wind-cold-dampness Bi-impediment. Methods:A total of 101 patients with KOA due to wind-cold-dampness Bi-impediment were divided into an acupuncture-medication group and a Chinese medication group using the random number table method.Fifty cases in the Chinese medication group took oral Fang Feng Xi Bi Tang for treatment,and 51 cases in the acupuncture-medication group received additional warming triple needling therapy.The symptom score of traditional Chinese medicine(TCM),inflammatory factor levels,and motor function of the knee joint were compared before and after treatment.The clinical efficacy was also compared between the two groups after treatment. Results:Three cases in the acupuncture-medication group and 2 cases in the Chinese medication group dropped out during the study,and the two groups each had 48 cases being included in statistical analysis ultimately.The total effective rate was 95.8%in the acupuncture-medication group,higher than 79.2%in the Chinese medication group,and the between-group difference was statistically significant(P<0.05).After treatment,the TCM symptom score dropped in both groups(P<0.05)and was lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β dropped after the intervention in both groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The scores of knee pain intensity,knee joint stiffness,and diurnal functioning decreased after treatment in the two groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05). Conclusion:Warming triple needling plus Fang Feng Xi Bi Tang can reduce inflammatory responses,improve daily functioning ability,and enhance the quality of life in patients with KOA due to wind-cold-dampness Bi-impediment.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective To investigate the effects of different dosages of atorvastatin, rosuvastatin, and simvastatin in elderly patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods A total of 180 patients with STEMI undergoing PCI were prospectively selected as study subjects and divided into group A, group B, group C, group D, group E, and group F using a random number table method, with 30 patients in each group. The group A received low-dose simvastatin orally, the group B received high-dose simvastatin orally, the group C received low-dose atorvastatin orally, the group D received high-dose atorvastatin orally, the group E received low-dose rosuvastatin orally, and the group F received high-dose rosuvastatin orally. The levels of serum inflammatory factors[interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP)], myocardial injury markers[creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP)], cardiac function indicators[left ventricular ejection fraction (LVEF), cardiac index (CI), cardiac output (CO)], as well as the ST-segment resolution, occurrence of adverse cardiovascular events, and adverse reactions were compared among the groups. Results At 1 day and 1 month postoperatively, the levels of IL-6, hs-CRP, and TNF-α decreased successively in groups A, B, C, D, E, and F(P < 0.05). At 1 day and 1 month postoperatively, the levels of cTnT, CK-MB, and NT-proBNP also decreased successively in the groups A, B, C, D, E, and F (P < 0.05). At 1 month postoperatively, the LVEF, CO, and CI increased successively in the groups A, B, C, D, E, and F (P < 0.05). The proportions of patients with ST-segment resolution successively increased in the groups A, B, C, D, E, and F (P < 0.05). There were no statistically significant differences in the total incidence of adverse cardiovascular events and adverse reactions among the groups (P>0.05). Conclusion Both low-dose and high-dose atorvastatin, rosuvastatin, and simvastatin can effectively relieve inflammation reactions, improve myocardial function, and promote ST-segment resolution in elderly patients with STEMI undergoing PCI, with high-dose rosuvastatin showing the best effect.

During the gene editing process mediated by CRISPR/Cas9, precise genome editing and gene knock-in can be achieved by the homologous recombination of double-stranded DNA (dsDNA) donor template. However, the low-efficiency of homologous recombination in eukaryotic cells hampers the development and application of this gene editing strategy. Here, we developed a novel CRISPR/Cas9-hLacI donor adapting system (DAS) to enhance the dsDNA-templated gene editing, taking the advantage of the specific binding of the LacI repressor protein and the LacO operator sequence derived for the Escherichia coli lactose operon. The codon-humanized LacI gene was fused as an adaptor to the Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus lugdunensis Cas9 (SlugCas9-HF) genes, and the LacO operator sequence was used as the aptamer and linked to the dsDNA donor template by PCR. The Cas9 nuclease activity after the fusion and the homology-directed repair (HDR) efficiency of the LacO-linked dsDNA template were firstly examined using surrogate reporter assays with the corresponding reporter vectors. The CRISPR/Cas9-hLacI DASs mediated genome precise editing were further checked, and we achieved a high efficiency up to 30.5% of precise editing at the VEGFA locus in HEK293T cells by using the CRISPR/SlugCas9-hLacI DAS. In summary, we developed a novel CRISPR/Cas9-hLacI DAS for dsDNA-templated gene editing, which enriches the CRISPR/Cas9-derived gene editing techniques and provides a novel tool for animal molecular design breeding researches.
Humans ; Animals ; Gene Editing ; CRISPR-Cas Systems/genetics* ; HEK293 Cells ; Homologous Recombination ; DNA

Objective:To study the clinical and laboratory characteristics of neonatal isolated sulfite oxidase deficiency (ISOD).Methods:An infant with neonatal ISOD admitted to our hospital was retrospectively analyzed. Using key words "isolated sulfite oxidase deficiency", "SUOX gene", "Infant, newborn", databases including CNKI, Wanfang database, National library and literature center of science and technology, China science paper online, PubMed, Web of Science and EMBASE (up to January 2021) were searched and literature review was conducted. The clinical manifestations, laboratory results, treatment and prognosis were analyzed.Results:Our patient was a full-term male infant with eye movement disorder, refractory seizures, feeding difficulties, increased muscle tone, developmental retardation and microcephaly. Urine sulfite paper-strip test was positive. Uric acid was normal. Whole exon sequencing (WES) revealed SUOX c.475G>T and c.1201A>G compound heterozygous mutations. Cranial MRI showed multiple encephalomalacia and brain atrophy at 5-month of age. The infant died at 8-month. In the literature review, a total of 29 articles and 32 cases of neonatal ISOD were found. 87.5% of the cases developed symptoms within 1-week after birth. All had convulsive seizures. Some of them had feeding difficulties, muscle tone changes, developmental retardation, microcephaly and ectopia lentis. Cranial imaging showed white matter cystic lesions and brain atrophy. Laboratory examination showed elevated urinary sulfite and S-sulfocysteine. Uric acid and xanthine/hypoxanthine were normal. Blood homocysteine was decreased. 23 cases received genetic testing and all of them had SUOX mutations. The treatment was mainly symptomatic relief and supportive treatment. During follow-up, 15 cases died, 13 cases survived and 4 cases were unknown. All the surviving children had drug-resistant convulsions and developmental retardation.Conclusions:Neonatal ISOD may present with refractory convulsions, feeding difficulties and developmental retardation. Cystic white matter changes and brain atrophy may be seen on cranial imaging. Elevated urinary sulfites, decreased blood homocysteine and normal uric acid are important clues for diagnosis. Genetic testing is helpful for early diagnosis.

Objective:To explore the perioperative effect of radial artery as a sequential graft in coronary artery bypass grafting(CABG).Methods:The clinical data and perioperative complications of 109 patients, who underwent radial artery(RA) or great saphenous vein(SVG) as a sequential graft during CABG from April 2020 to December 2020 in Beijing Anzhen Hospital, were analyzed, there were 86 males and 23 females, aged from 39 to 79 years, with an average of(61.1±8.0)years old. According to the graft materials, they were divided into the RA group(n=47) and SVG group(n=62).Results:There were no significant differences between the two groups in age, gender, comorbidities, echocardiographic results, transplant vascular indexes, coronary angiography results, and operation methods(on-pump or off-pump, use of left internal mammary artery, number and distribution of distal anastomoses)( P>0.05). There were also no significant difference between the two groups in ICU stay, postoperative hospital stay and drainage with 24 hours after CABG( P>0.05). The incidence of postoperative cerebrovascular events, postoperative infection and secondary thoracotomy in the RA group were higher than that in the SVG group. The incidence of myocardial infarction, postoperative ventricular arrhythmia and postoperative IABP assistance in the SVG were higher than that in the RA group, but the difference was not statistically significant( P>0.05). Conclusion:The application of radial artery as a sequential graft during CABG does not increase the risk of perioperative complications, and the patients recover smoothly.

Objective    To explore coronary angiographic characteristics in patients with symptomatic recurrence after coronary artery bypass grafting (CABG). Methods    We performed a retrospective study of 997 patients with symptomatic recurrence after CABG in Beijing Anzhen Hospital from 2010 to 2020. There were 762 males and 235 females, with an average age of 62.41±8.70 years. Results    There was a high prevalence of risk factors like hypertension, diabetes and a history of smoking. Diseased arterial grafts accounted for 27.44% while saphenous vein graft 54.40%; 240 (24.07%) patients had all patent grafts. The main lesion characteristics of diseased grafts were chronic total occlusion lesions (79.57%). Most patients had more diseased native vessels after CABG than before. The type C coronary artery disease in native vessels relevant to ischemic area occurred in 674 (67.60%) patients; 525 (52.66%) patients with recurrent symptom after CABG had both diseased grafts and diseased native vessels. Conclusion     Graft status in patients with symptomatic recurrence after CABG is worse than we expected. The majority have newly developed lesions both in grafts and native vessels. Native vascular lesions will continue to progress after CABG.