Objective:To develop a nucleic acid detection system for Helicobacter pylori ( H. pylori) based on recombinase-aided isothermal amplification (RAA) and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated(Cas13a). Methods:Thirty strains of H. pylori, as well as two strains each of Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae were collected from the Emergency General Hospital between 2021 and 2022. The specific primers and CRISPR RNA (crRNA) required for this newly established method were designed based on the conserved region of the ureC gene of H. pylori. Then, the primer pair that produced the least non-specific products was screened out using agarose gel electrophoresis, and the crRNA sequence with the highest cleavage efficiency was screened according to the fluorescence intensity produced by Cas13a cutting fluorescence probe. The RAA-Cas13a nucleic acid detection system was developed, and the limit of detection and the specificity of which were evaluated by detecting gradient dilutions of H. pylori ATCC 43504 genomic DNA and 5 different clinically common pathogens′ genomic DNA. The consistency with quantitative real-time PCR(qPCR) method was obtained by simultaneously detecting clinical strains using this method and established qPCR method. Two-tailed paired t-test was used to compare the fluorescence results between the two groups, and a P value less than 0.05 indicates a statistically significant difference. Results:The established RAA-Cas13a nucleic acid detection system could detect target DNA as low as 10 copies/μl. within 1 hour ( t=11.05, P<0.01), without cross-reaction with the other 5 clinically common strains. That method also showed good consistency compared to the qPCR method, the kappa coefficient=1. Conclusions:A method combining RAA with CRISPR-Cas13a for detecting H. pylori has been established, which can be used for rapid and sensitive identification of H. pylori infection.

Background: and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. Methods: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Results: Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). Conclusion CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Objective:To explore the relationship between thyroid hormone sensitivity and obesity phenotype in people with normal thyroid function.Methods:In this retrospective study, 6155 euthyroid subjects who underwent a health check-up in the First Hospital of China Medical University between January 2017 and December 2018 were included. Participants were categorized into four obesity phenotypes according to body mass index and metabolic status. Thyroid Feedback Quantile-based Index(TFQI), Parametric TFQI, free triiodothyronine to free thyroxine ratio(FT 3/FT 4), and sum activity of peripheral deiodinases(SPINA-GD) were calculated to evaluate thyroid hormone sensitivity. Results:Compared with metabolically healthy non-obese(MHNO) phenotype, the subjects with metabolically healthy obese(MHO) or metabolically unhealthy obese(MUO) phenotype showed higher FT 3/FT 4ratio. Metabolically unhealthy non-obese(MUNO) and MUO subjects showed lower TFQI. After adjusting for confounders, FT 3/FT 4ratio was positively associated with MHO( OR 1.18, 95% CI 1.11-1.26) and MUO phenotype( OR 1.28, 95% CI 1.19-1.39). With 1 s increase of TFQI, the OR for MUNO phenotype was 0.77(95% CI 0.64-0.94). The results of Parametric TFQI and SPINA-GD were similar to TFQI and FT 3/FT 4ratio, respectively. Conclusion:In euthyroid individuals, thyroid hormone sensitivity was positively associated with increased risk for unhealthy obesity phenotypes.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

Objective:To analyze the factors affecting the relative height change of the patella after primary robotic-assisted total knee arthroplasty (R-TKA).Methods:The data of 97 patients with osteoarthritis of the knee treated with R-TKA admitted from June 2021 to March 2022 were retrospectively analyzed, including 15 males and 82 females, aged 70.0±5.4 years (range, 58-80 years). The bone resection parameters of the robotic system were recorded intraoperatively, including the bone resection amount of the medial and lateral distal femur, medial and lateral posterior femoral condyle and medial and lateral tibial plateau. The Blackburne-Peel index (BPI) and Caton-Deschamps index (CDI) were used to measure the preoperative and postoperative relative patellar height on lateral radiographs, as well as the posterior tibial slope (PTS) and the change in patellar ligament length before and after surgery. The relationship between the change in relative patellar height and the variables of interest was analyzed using partial correlation and multiple linear regression.Results:The mean postoperative CDI was lower than preoperatively (0.79±0.15 vs. 0.91±0.13, t=9.69, P<0.001), and the percentage of patients with postoperative CDI<0.6 was higher than preoperatively (9.3% vs. 0; χ 2=12.92, P<0.001); the differences in mean postoperative BPI and percentage of patients with postoperative BPI<0.45 were not statistically significant compared to preoperatively (0.69±0.13 vs. 0.71±0.17, t=1.35, P=0.182; 11.3% vs. 17.5%, χ 2=1.50, P=0.220). The mean patellar ligament length on the first postoperative day was 2.29 mm shorter than preoperatively, there was a statistically significant difference ( t=5.90, P<0.001). Partial correlation analysis showed that the amount of patellar ligament length change was positively correlated with the amount of BPI and CDI change ( r=0.84, P<0.001; r=0.70, P<0.001), and the amount of PTS change and the mean distal femoral bone resection were negatively correlated with the amount of BPI ( r= -0.41, P<0.001; r=-0.32, P=0.002) and CDI ( r=-0.23, P=0.029; r=-0.25, P=0.017) change. In contrast, the amount of posterior femoral condyle bone resection and tibial plateau bone resection did not correlate with the change of BPI and CDI. Multiple linear regression analysis showed that the amount of patellar ligament length change, PTS change and the distal femoral bone resection were factors influencing the change of BPI ( β=0.03, P<0.001; β=-0.01, P<0.001; β=-0.02, P=0.021) and CDI ( β=0.02, P<0.001; β=-0.01, P=0.001; β=-0.02, P=0.008). Conclusion:Amount of patellar ligament length change, PTS change and the distal femoral bone resection are factors affecting the BPI. In order to obtain a better relative patellar height in the primary R-TKA, attention should be paid to the adjustment of the distal femoral bone resection and PTS, while taking the necessary measures to reduce the postoperative patellar ligament length changes.

With the rapid development of healthcare big data and artificial intelligence technology, how to utilize the massive medical data generated based on clinical diagnosis and treatment has become an important issue to be solved in the field of clinical research. Clinical diagnosis and treatment data is an essential part of healthcare big data, and also the main field of healthcare big data research. With the continuous deepening and extensive development of informatization, hospitals have accumulated a large number of patient-centered clinical diagnosis and treatment data. Deeply mining and analyzing these data through big data technology can provide reference for precise diagnosis and treatment, and standardized prevention and control of diseases. However, conducting relevant research still faces many difficulties and blockages, such as the increased risk of data leakage or abuse, and the difficulty in implementing informed consent. To safely, legally and efficiently utilize clinical diagnosis and treatment data to conduct clinical research and fully tap into the value of these precious medical resources, a tertiary hospital in Beijing has built a research big data platform and developed relevant systems to effectively solve the problems of blockages and difficulties in the application of rich clinical resources to clinical research, and improve the service quality of medical institutions and the conversion rate of scientific research achievements. By introducing the key points and management methods in the implementation of clinical research based on the scientific research big data platform, analyzing and exploring the existing problems and improvement measures, this paper aimed to provide theoretical basis and system reference for high-quality and efficient health and medical big data clinical research, inspire and promote the continuous improvement of medical research management, and promote the development of medical and health science and technology innovation.

The 24th National Conference of Neurology of Chinese Medical Association was held in Zhuhai City, Guangdong Province during September 23-26,2021.The conference adopted a combination of online and offline methods, with a total of 2 plenary meetings, 20 special seminars, 284 invited reports, 382 papers exchanged at the conference and 1 088 papers exchanged on the wall. The conference focused on cerebrovascular diseases, epilepsy, cognitive disorders, myopathy, peripheral neuropathy, neurodegenerative diseases, nerve infectious diseases, demyelinating diseases, neuroimmune diseases, genetic and metabolic nerve diseases, nerve rehabilitation, anxiety and depression, headache, sleep disorders, nerve nursing, nerve intervention, neuroimaging, neuroelectrophysiology, translational medicine, precision medicine and other related nervous system diseases. There were more than 7 000 participants who attended this conferece.

Atherosclerosis is one of the most common cardiovascular and cerebrovascular diseases, and it is also an important cause of stroke. However, the research on the pathogenesis of atherosclerosis is still incomplete. Single cell technology, as an emerging technology in the study of differences in cell biology, has become a new tool and provides a new way of exploring the etiology of atherosclerosis. This article reviewed the research progress of single cell sequencing technology in atherosclerosis in recent years.

Background: and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. Methods: Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. Results: Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

Humans ; Ischemic Attack, Transient ; Recurrence ; Risk Factors ; Stroke/epidemiology*