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.

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.

Objective:To explore the effects of different polymers on in vitro biomimetic mineralization of small intestinal submucosa(SIS)scaffolds,and to evaluate the physicochemical properties and bio-compatibility of the SIS scaffolds.Methods:The SIS scaffolds prepared by freeze-drying method were im-mersed in simulated body fluid(SBF),mineralized liquid containing polyacrylic acid(PAA)and mine-ralized liquid containing PAA and polyaspartic acid(PASP).After two weeks in the mineralized solu-tion,the liquid was changed every other day.SBF@SIS,PAA@SIS,PAA/PASP@SIS scaffolds were ob-tained.The SIS scaffolds were used as control group to evaluate their physicochemical properties and bio-compatibility.We observed the bulk morphology of the scaffolds in each group,analyzed the microscopic morphology by environment scanning electron microscopy and determined the porosity and pore size.We also analyzed the surface elements by energy dispersive X-ray spectroscopy(EDX),analyzed the struc-ture of functional groups by Flourier transformed infrared spectroscopy(FTIR),detected the water ab-sorption rate by using specific gravity method,and evaluated the compression strength by universal me-chanical testing machine.The pro-cell proliferation effect of each group of scaffolds were evaluated by CCK-8 cell proliferation method.Results:Under scanning electron microscopy,the scaffolds of each group showed a three-dimensional porous structure with suitable pore size and porosity,and crystal was observed in all the mineralized scaffolds of each group,in which the crystal deposition of PAA/PASP@SIS scaffolds was more regular.At the same time,the collagen fibers could be seen to thicken.EDX analysis showed that the characteristic peaks of Ca and P were found in the three groups of mineralized scaffolds,and the highest peaks were found in the PAA/PASP@SIS scaffolds.FTIR analysis proved that all the three groups of mineralized scaffolds were able to combine hydroxyapatite with SIS.All the scaf-folds had good hydrophilicity.The compressive strength of the mineralized scaffold in the three groups was higher than that in the control group,and the best compressive strength was found in PAA/PASP@SIS scaffold.The scaffolds of all the groups could effectively adsorb proteins,and PAA/PASP@SIS group had the best adsorption capacity.In the CCK-8 cell proliferation experiment,the PAA/PASP@SIS scaffold showed the best ability to promote cell proliferation with the largest number of living cells observed.Con-clusion:Compared with other mineralized scaffolds,PAA/PASP@SIS scaffolds prepared by mineralized solution containing both PAA and PASP have better physicochemical properties and biocompatibility and have potential applications in bone tissue engineering.

Objective The management of high-value medical consumables is a key challenge for healthcare institutions,yet medical record quality control(MRQC)is rarely applied in this area.This study aims to explore the role of MRQC in the management of high-value medical consumables.Methods A joint inspection team for MRQC was formed.Using the"High-Value Consumable Use Informed Consent Checklist,""High-Value Consumable Medical Record Sampling Statistics Table,""Surgical Operation Record Inspection Detail Table,"and"High-Value Medical Consumable Usage List Barcode Inspection Table,"we conducted random checks on the medical records of the top ten departments with high usage of these consumables.The main focus was on the informed consent forms,surgical operation records,barcode labeling of usage lists,and expense lists related to high-value medical consumables.We analyzed the consistency and compliance of registration information,informed consent forms,surgical records,and barcode labels,calculated defect rates for each indicator,identified causes of defects,and implemented quality improvements,including refining regulations and enhancing training;conducting reviews of high-value con-sumable medical records;initiating secondary management of high-value consumables;strengthening supervision;and establis-hing a long-term mechanism.Results Before improvements,the defect rates for informed consent forms,surgical records,and barcode labels were 13.3％,27.9％,and 42.7％,respectively.After improvements,these rates dropped to 1.4％,2.2％,and 1.6％.Comparisons of the three indicators before and after showed significant differences(P＜0.01).Conclusion The appli-cation of MRQC in managing high-value medical consumables is essential.Through medical record checks,we can achieve the"five checks and five correspondences"regarding the registration information of high-value medical consumables,informed con-sent forms,written records in surgical operation records,barcode labeling of usage lists,and expense lists.The key to successful implementation is thorough preparation before inspections,interdepartmental collaboration,problem-oriented self-assessment,strict discipline,and continuous improvement.

Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Objective:To explore the impact of adverse childhood experience on self-injury behavior and the mediating role of self hating in adolescents.Methods:A cross-sectional survey was conducted in 6 high schools and 5 middle schools in Shandong Province from August 1 to December 31, 2022, using the adverse childhood experience questionnaire, self-hating scale and non-suicidal self-injury behavior rating questionnaire for adolescents. A total of 7 313 questionnaires were collected, of which 6 948 were valid. SPSS 22.0 software was used for Spearman correlation analysis, and biased-corrected non-parametric percentile Bootstrap method was used to test the significance of mediating effect.Results:(1) The scores of adverse childhood experience(4.0(2.0, 6.0)), self-hating (22.0 (13.0, 29.0)) and self-injury behavior (12.0 (7.0, 19.0)) in adolescents with self-injury behavior were higher than those without self-injury behavior(0(0, 2.0), 2.0(0, 9.0), 0(0, 1.0)), and the differences were statistically significant ( Z=-21.700, -22.654, -29.519, all P<0.001). (2) Adverse childhood experience was positively correlated with self-hating ( r=0.46, P<0.01) and self-injury behavior ( r=0.47, P<0.01). Self-hating was positively correlated with self-injury behavior ( r=0.51, P<0.01). (3) Adverse childhood experience directly predicted self-injury behavior with a direct effect of 0.163 (95% CI =0.127-0.200, P<0.01)and the effect size of 53.80%(0.163/0.303).Adverse childhood experiences indirectly predicted self-injury behavior through self-hating, with an indirect effect of 0.140 (95% CI=0.122-0.160, P<0.001) and the effect size of 46.20%(0.140/0.303).The total effect was 0.303 (95% CI=0.270-0.336, P<0.001). Conclusions:There is a close relationship between adverse childhood experiences, self-hating and self-injury behavior in adolescents. Adverse childhood experiences can directly predict self-injury behavior, and can also indirectly affect self-injury behavior through self-hating.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

OBJECTIVE To establish the path-based management mode of 5-hydroxytryptamine-3 receptor antagonist （5- HT3RA） in chemotherapy patients， and to improve the rationality of medication in chemotherapy patients. METHODS 5-HT3RA standardized drug use control rules were formulated， with the help of medical intelligence and decision support （MINDS） system， path-based management was carried out for chemotherapy patients using 5-HT3RA in the form of whole-process information capture and prescription pre-review， and whole-process intervention was implemented on medication indications， usage and dosage， course of treatment， etc. The intervention effect was analyzed by comparing the changes in the use of 5-HT3RA without indication， unreasonable usage and dosage， repeated medication， unreasonable course of treatment， and per capita drug cost before and after the implementation of path-based management. RESULTS A total of 9 181 patients were included. After the implementation of path- based management， the proportion of unindicated drugs decreased by 0.48%， and the rate of unreasonable single dosage， unreasonable frequency， repeated medication， unreasonable treatment course （5-HT3RA still used 3 days after chemotherapy） decreased by 10.48%， 0.65%， 1.33% and 0.34%； per capita cost of 5-HT3RA decreased by 13.72 yuan； there were statistical significance （P＜0.05）. CONCLUSIONS 5-HT3RA path-based management mode effectively improves the rationality of medication and provides a new idea for rational clinical drug use.