1.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
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.
2.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
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.
3.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
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.
4.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
5.Development and Application of a Micro-device for Rapid Detection of Ammonia Nitrogen in Environmental Water
Peng WANG ; Yong TIAN ; Chuan-Yu LIU ; Wei-Liang WANG ; Xu-Wei CHEN ; Yan-Feng ZHANG ; Ming-Li CHEN ; Jian-Hua WANG
Chinese Journal of Analytical Chemistry 2024;52(2):178-186,中插1-中插3
The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.
6.Value of evaluating Graves ophthalmopathy motiliny by MRI T2-mapping
Lu WANG ; Yao FAN ; Jian LONG ; Ming-Qiao ZHANG ; Chun LIU
Medical Journal of Chinese People's Liberation Army 2024;49(1):70-74
Objective To investigate the value of magnetic resonance imaging(MRI)T2-mapping in evaluating the activity of Graves ophthalmopathy(GO).Methods A total of 64 patients with GO in the Department of Endocrinology,the First Affiliated Hospital of Chongqing Medical University from July 2019 to January 2021 were collected.Simple random grouping was performed by computer,with 49 cases as observation subjects,and 15 patients for diagnostic test.According to clinical activity score(CAS),49 GO patients were divided into active group(CAS≥3 points,48 eyes)and inactive group(CAS<3 points,50 eyes).Normal control group(NC group)included 31 patients(62 eyes).All subjects underwent 3.0T orbital MRI T2-mapping.Measuring the T2 relaxation time(T2RT)of superior rectus,inferior rectus,medial rectus,and lateral rectus on five layers behind the eyeball on T2-mapping coronal images,and select the maximum value of T2RT in the five layers for each extraocular muscle to represent the T2RT of this extraocular muscle.Finally,select the maximum T2RT values of the four extraocular muscles,expressed as extraocular muscle maximum T2RT.Compare the differences of the above 5 indicators(superior rectus T2RT,inferior rectus T2RT,medial rectus T2RT,lateral rectus T2RT,extraocular muscle maximum T2RT)between active group,inactive group and NC group.ROC curve was used to analyze the diagnostic value of the above 5 indicators for GO activity assessment,and the diagnostic threshold was obtained.Then,another 15 GO patients were performed for diagnostic tests evaluation to determine the indicators of high diagnostic efficacy and the threshold of diagnostic activity.Results The T2RT of all extraocular muscles in active group were significantly higher than those in inactive group and NC group,the difference was statistically significant(P<0.001).The threshold value of the five indicators were obtained by ROC curve analysis.The maximum T2RT cut-off values of superior rectus muscle,inferior rectus muscle,medial rectus muscle,lateral rectus muscle and extraocular muscles for judging activity were 80.200 ms,97.045 ms,94.355 ms,85.750 ms and 101.385 ms respectively.Another 15 GO patients were performed for diagnostic tests,the indexes with relatively high sensitivity,specificity,positive predictive value and negative predictive value were inferior rectus T2RT and extraocular muscle maximum T2RT,the cut-off values of GO activity were 97.045 ms and 101.385 ms,respectively;the sensitivity were 91.7%and 93.8%,respectively;the specificity all were 80.0%.Conclusions MRI T2-mapping sequence has a good value in assessment of GO activity.The inferior rectus T2RT and extraocular muscle maximum T2RT can be choosed to evaluate the activity of GO.
7.Assessment of health emergency drill capacity for poisoning incidents at the municipal level in Guangdong Province
Jiaxin JIANG ; Shanyu ZHOU ; Xinyu LIU ; Xiaoyong LIU ; Jian HUANG ; Ming LIU ; Yongshun HUANG ; Xudong LI
China Occupational Medicine 2024;51(1):94-98
ObjectiveTo assess the capacity of health emergency drills for poisoning emergencies at the municipal level in Guangdong Province. Methods A total of 21 municipal teams from cities in Guangdong Province participated in the health emergency drill competition, which included comprehensive tests and practical assessments. Results The pass rate for the total score, comprehensive tests, practical assessments of 21 municipal teams was 66.7%, 33.3%, 66.7%, respectively. The pass rate of the comprehensive tests was lower than that of practical assessments (P<0.01). The pass rate for the total score, comprehensive tests, and practical assessments of team from the Pearl River Delta region was higher than those in non-Pearl River Delta regions (88.9% vs 50.0%, 55.5% vs 16.7%, 88.9% vs 50.0%). For the four comprehensive test items, the highest pass rate was for personal protective principles against chemical poisoning (57.1%). For the five practical assessment items, the highest pass rate was for the selection and matching of personal protective equipment and practice of poisoning detection (both 71.4%). Conclusion It is urgent to improve the capacity of health emergency drills at the municipal level in Guangdong Province. Emphasis should be placed on strengthening capacity building in teams from non-Pearl River Delta regions.
8.miR-375 Attenuates The Migration and Invasion of Osteosarcoma Cells by Targeting MMP13
Zhong LIU ; Lei HE ; Jian XIAO ; Qing-Mei ZHU ; Jun XIAO ; Yong-Ming YANG ; Yong-Jian LUO ; Zhong-Cheng MO ; Yi-Qun ZHANG ; Ming LI
Progress in Biochemistry and Biophysics 2024;51(5):1203-1214
ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.
9.Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections
Zhuo-Jun HE ; Yu-Ying CHEN ; Yang ZHOU ; Gui-Qin DAI ; De-Liang LIU ; Meng-De LIU ; Jian-Hui GAO ; Ze CHEN ; Jia-Yu DENG ; Guang-Yan LIANG ; Li WEI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2024;51(7):1604-1617
Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
10.Effect of vitamin C on intestinal flora disorders in Cr(VI)-contaminated mice
Limin ZHANG ; Chen LIU ; Yumei LIU ; Xueqian WU ; Ming SHU ; Jian ZHOU ; Dongqun XU ; Qin WANG ; Wanwei LI ; Xiaohong LI
Journal of Environmental and Occupational Medicine 2024;41(7):807-813
Background Hexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. Objective To investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. Methods Thirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K2Cr2O7, Cr(VI)], and VC+K2Cr2O7 [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K2Cr2O7 solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K2Cr2O7 solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg−1, and the dose of K2Cr2O7 was 1.25 mg·kg−1. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. Results The Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P<0.05), the PD whole tree index in the Cr(VI) group was 27.863±2.399, which was significantly higher than that in the Con group (P<0.05), and the VC intervention significantly reversed the changes of the above indexes due to Cr(VI) exposure (P<0.05). In the β diversity analysis, the principal coordinates analysis (PCoA) results showed a significant separation between the Cr(VI) group and the Con group, and after the VC intervention, there was a retraction of the separation trend and the difference was reduced. The multi-sample similarity dendrogram results showed that the control and the VC groups clustered together first, then with the VC+Cr(VI) group, and finally with the Cr(VI) group. The abundances of Bacteroidetes, Saccharibacteria, and Tenericutes in the intestine of mice in the Cr(VI) group were decreased, and the abundance of Firmicutes was increased; the abundances of Lactobacillus, Alistipes, Bacteroides, and Ruminiclostridium were also increased. Included among these, Bacteroides showed a significantly higher abundance compared to the control mice (P<0.05). Changes in the abundances of phyla and genera of the above mentioned gut microorganisms were reversed after the VC intervention. Conclusion Cr(VI) exposure can lead to intestinal damage and disorganization of the intestinal flora structure in mice, while VC intervention can ameliorate the above changes to a certain extent and normalize the intestinal flora structure.

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