Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

Objective:To explore the effectiveness of a hysteroscopic endometrial lesion diagnosis model de-veloped based on deep learning(DL)algorithm combined with gradient-weighted class activation mapping(Grad-CAM)visualization technology.Methods:303 hysteroscopy videos(4781 images)of 291 patients who un-derwent hysteroscopy examination in the Department of Gynecology,Renmin Hospital of Wuhan University from June 1,2021 to December 31,2022 were selected.The dataset was divided into a training set(3703 images)and a test set(1078 images)by weight sampling method.After the training set was used for model learning and train-ing,two model architectures,residual neural network(ResNet18)and efficient neural network(EfficientNet-B0),were selected to verify the model in the test set by five-class and two-class classification tasks,respectively.Tak-ing histopathology as the gold standard,the diagnostic efficacy was evaluated to select the optimal model,and the Grad-CAM layer was embedded in the optimal model to output hysteroscopy images of Grad-CAM.Results:①In the five-class classification tasks,the accuracy of EfficientNet-B0 model(93.23％)was higher than that of Res-Net18 model(84.23％);the area under the curve(AUC)of EfficientNet-B0 model in the diagnosis of five disea-ses,including atypical endometrial hyperplasia,endometrial polyps,endometrial cancer,endometrial atypical hy-perplasia,and submucous myoma,was slightly higher than that of ResNet18 model,and the AUC of both models was almost above 0.980.②In the binary classification task of accuracy and the evaluation of specificity,the two models were similar,both above 93.00％,and the sensitivity of EfficientNet-B0 model(91.14％)was significantly better than that of ResNet18 model(77.22％).③EfficientNet-B0 model combined with Grad-CAM algorithm could identify the abnormal areas in the image.After biopsy and pathological examination,it was confirmed that about 95％of the marked areas in the model's output heatmap were lesion areas.Conclusions:The hysteroscopy di-agnostic model developed by EfficientNet-B0 model combined with Grad-CAM has high diagnostic accuracy,sen-sitivity,and specificity,and has application value in the diagnosis of endometrial lesions.

Objective To explore the effect and mechanism of hydroxysafflor yellow A(HSYA)on autophagy in bEnd.3 cells after oxygen-glucose deprivation(OGD).Methods The bEnd.3 cells were divided into normal group(conventional culture),model group(OGD model),HSYA group(OGD model+75 μmol·L-1 HSYA),3-methyladenine(3MA)group(5 mmol·L-1 3MA+OGD model)and 3 MA+HSYA group(5 mmol·L-1 3 MA+OGD model+75 μmol·L-1 HSYA).The level of apoptosis was determined by TUNEL fluorescence staining;Western blot was used to detect the expression of autophagy,blood brain barrier(BBB)related proteins;real time fluorescence quantitative polymerase chain reaction method for determining the expression of sirtuin-1(SIRT1)and forkhead box protein O3a(FOXO3A)mRNA.Results In the normal group,model group,HSYA group,3MA group and 3MA+HSYA group,the positive cells selected for TUNEL staining were 5.00±1.00,28.00±2.00,21.00±3.00,35.33±2.51 and 29.67±2.52;the expression levels of microtubule-associated protein 1 light chain 3-Ⅱ/-Ⅰ(LC3-Ⅱ/-Ⅰ)were 0.90±0.20,1.34±0.10,1.95±0.14,0.76±0.15 and 1.14±0.09;sequestosome 1(P62)were 0.99±0.02,0.60±0.02,0.38±0.01,0.67±0.04 and 0.54±0.01;occludin were 1.39±0.17,0.62±0.15,1.00±0.09,0.40±0.13 and 0.80±0.15;zonula occludens-1(ZO-1)were 1.63±0.20,0.64±0.06,0.98±0.14,0.37±0.14 and 0.87±0.04;SIRT1 mRNA were 1.00±0.00,0.75±0.07,1.69±0.09,0.31±0.02 and 0.56±0.01;FOXO3A mRNA were 1.00±0.00,0.80±0.05,1.47±0.09,0.40±0.01 and 0.62±0.09,respectively.Significant differences were found between model group and normal group,HSYA group and model group,3MA+HSYA group and 3MA group(P＜0.05,P＜0.01,P＜0.001).Conclusion HSYA may enhance autophagy levels in bEnd.3 cells after OGD through the SIRT1/FOXO3A pathway,inhibit cell apoptosis and alleviate BBB damage.

Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.