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.Association of cumulative pulse pressure levels with the risk of metabolic syndrome
Peimeng ZHU ; Jingfeng CHEN ; Su YAN ; Youxiang WANG ; Haoshuang LIU ; Jiaoyan LI ; Suying DING
Chinese Journal of Endocrinology and Metabolism 2024;40(10):858-866
Objective:To explore the potential correlation between cumulative pulse pressure (cumPP) level and metabolic syndrome (MetS), and to provide insights for MetS management.Methods:A total of 3 968 subjects who underwent health checkup were selected to form a research cohort, and the data were categorized into three groups based on the tertiles of cumPP levels. Cox proportional hazards regression model was employed to analyze the association between different cumPP levels and the incidence of new-onset MetS. Results:The risk of MetS increased with the increased tiers of the cumPP levels (2.5%, 4.3%, and 4.6%, Ptrend<0.001) during the median follow-up period of 2.16 years. Spearman rank correlation analysis showed that cumPP was positively correlated with waist circumference, systolic blood pressure, diastolic blood pressure and fasting plasma glucose (all P<0.05). The Cox proportional hazards regression adjusted model showed that the risk of MetS in Q2 and Q3 was higher than that in Q1 in the total population, and the same results were observed in males (all P<0.05), while there was no statistical significance in females. Model 3 of the total population adjusted for a variety of confounding factors displayed a higher risk of MetS in Q3 compared with that in Q1[1.654 (95% CI 1.272-2.151) ]. When stratified by sex, and the risk of MetS in Q3 was 1.665 times higher than that in Q1 (95% CI 1.245-2.227), while there was no statistically significant risk in female. According to the visual nomogram of independent risk factors screened by multivariate analysis based on Cox proportional hazards regression model, the incidence of MetS at 1 year, 2 years, and 3 years was 0.18%, 3.97% and 7.39%, respectively. In addition, the dose-response curve was plotted according to cumPP, suggesting that the risk of MetS gradually increased with the increase of cumPP in the total population. Subgroup analyses based on baseline systolic blood pressure levels showed that higher cumPP levels were associated with a higher risk of developing MetS, regardless of whether systolic blood pressure was abnormal. Conclusions:Elevated cumPP levels is significantly related to the incidence of new-onset MetS. Maintaining pulse pressure within an appropriate range over long term is crucial for the management of MetS.
5.Glutamyl transpeptidase trajectories and new-onset metabolic syndrome: A cohort study
Youxiang WANG ; Jingfeng CHEN ; Su YAN ; Jiaoyan LI ; Haoshuang LIU ; Qian QIN ; Tiantian LI ; Suying DING
Chinese Journal of Endocrinology and Metabolism 2023;39(2):112-117
Objective:To explore the association between glutamyl transpeptidase (GGT) trajectories and new-onset metabolic syndrome to provide insights for the prevention and treatment of metabolic syndrome.Methods:A total of 3 209 subjects who met the inclusion criteria were enrolled in the study cohort of physical examination population. The GGT levels before follow-up were classified by R LCTMtools program into 3 GGT trajectory groups: low-stable group, medium-stable group and high-stable group. Cox proportional hazards regression model was used to analyze the correlation between different GGT trajectories and new-onset metabolic syndrome.Results:At the end of follow-up in 2020, the cumulative incidence of metabolic syndrome was 7.0%, and the incidence of metabolic syndrome in the low-stable group, medium-stable group and high-stable group were 3.9%, 11.4%, and 15.0%, respectively, showing a growth trend ( P<0.001). After adjusting for multiple confounding factors by Cox proportional hazards regression model, the risk of metabolic syndrome in medium-stable group and high-stable group increased in the total population. The hazard ratios (95% CI)for the high stable group in males and the medium-stable group in females were 1.67(1.07-2.60) and 3.29(1.14-9.53), respectively, compared with their respective low-stable group. Conclusion:Elevated longitudinal trajectory of GGT is a risk factor for new-onset metabolic syndrome, the risk of metabolic syndrome in the total population increased with the increase of long-term GGT level. It is recommended to maintain the long-term level of GGT at about 28 U/L in males and 14 U/L in females, respectively, to achieve the goal of early prevention of metabolic syndrome.
6.Clinical and epidemiological analysis of 18 cases of Japanese spotted fever in Zigui County
Ping GONG ; Xin CHEN ; Junlin LU ; Haixia SHI ; Youxiang KOU ; Changzhen WANG ; Faming GONG ; Xuefen QIN ; Jiannan ZHOU ; Xuebing LIN
Chinese Journal of Laboratory Medicine 2023;46(2):150-154
Objective:The epidemiological and clinical characteristics of 18 cases of Japanese spotted fever (JSF) in Zigui County were analyzed in order to improve the prevention and treatment of JSF.Methods:This is a case series analysis. The epidemiological and clinical data, laboratory tests and imaging characteristics of 18 JSF cases with median age of 60 years (54, 68) identified by The People′s Hospital of Zigui from April 2021 to August 2022 were collected and analyzed retrospectively.Results:Most (17/18) of the patients were farmers and all had a field exposure history. The patient′s onset was from April to October. Spring and autumn were the seasons with the highest incidence of JSF. The first symptoms of patients were high fever, headache, and fatigue. Of the 18 cases, 15 had a rash and 12 presented an eschar and 3 had neither rash nor eschar. In addition, 10 of 18 cases experienced edema of both lower extremities, and 3 got disturbance of consciousness. Laboratory tests found that 15 patients had abnormal white blood cells and 11 patients had decreased platelets. C-reactive protein, procalcitonin, D-dimer, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase were elevated in all patients; 13 patients with elevated alanine aminotransferase, 14 patients with elevated aspartate transamination. Kidney damage caused by Rickettsia japonica infection showed by abnormal proteinuria in 11 of the patients. Conclusions:The most common clinical manifestations of JSF are non-specific indications such as high fever, chills, fatigue, headache. The eschar and rash, which are the main features of Rickettsia infection, are not present in all patients, resulting delay of diagnosis or misdiagnosis. Medical workers should be more alert to rickettsial infections in patients with fever of unknown origin, especially in seasons of high incidence of spotted fever. Early diagnosis and correct antibiotic treatment shall be given according to the patient′s clinical manifestations, laboratory results and imaging test to control disease progression.
7.The bidirectional relationship between long-term dynamic alanine aminotransferase level and metabolic associated fatty liver disease
Jingfeng CHEN ; Zhuoqing WU ; Su YAN ; Youxiang WANG ; Xiaoqin SONG ; Suying DING
Chinese Journal of Endocrinology and Metabolism 2023;39(12):1028-1036
Objective:To explore the relationship between the long-term dynamic change in alanine aminotransferase(ALT) level and metabolic associated fatty liver disease(MAFLD).Methods:A retrospective study was conducted on 6 864 subjects who underwent four consecutive physical examinations from 2017 to 2020 in a cohort study of physical examination population in Henan Province. The relation between ALT level and the shift of MAFLD risk was analyzed using a multi-state Markov model, and the bidirectional relationship between ALT level and MAFLD was explored using a random intercept cross-lagged model.Results:Multi-state Markov model after adjusting for confounding factors showed that the risk of MAFLD in ALT Q2, Q3, Q4 group was gradually higher than that in Q1 group; Compared with health status, non-alcoholic fatty liver disease and MAFLD status gradually increased the risk of ALT shifting from normal to abnormal. The random intercept cross-lagged model after adjusting for confounding factors showed that there was a significant positive bidirectional relationship between MAFLD and ALT level. The cross-lag effect of MAFLD→ALT level was 0.083(95% CI 0.078-0.087), and the cross-lag effect of ALT→MAFLD was 0.044(95% CI 0.039-0.050). And with the extension of time, the cross-lag effect gradually decreased. Conclusions:There is a significant bidirectional relationship between the long-term dynamic change of ALT level and MAFLD. The occurrence of MAFLD is more likely to increase the risk of elevated ALT level, emphasizing the need for enhanced early prevention and treatment of MAFLD.
8.Construction of severe fever with thrombocytopenia syndrome virus recombinant pseudoviruses and effect of Gc glycosylation on viral infectivity
Xiaowen CHONG ; Zequn WANG ; Mengting CHEN ; Mengyu DU ; Xiaoying XU ; Youxiang MA ; Hongling WEN
Chinese Journal of Experimental and Clinical Virology 2023;37(6):583-591
Objective:To explore the relationship between severe fever with thrombocytopenia syndrome virus (SFTSV) Gc and its N-glycosylation site and viral infectivity, a recombinant pseudovirus containing SFTSV Gc glycosylation site mutant was constructed.Methods:The eukaryotic expression vectors pcDNA3.1(+ )-GC, PCDNA3.1(+ )-GC(N291Q), PCDNA3.1(+ )-GC(N352Q) and PCDNA3.1(+ )-GC (N374Q) were constructed by site-directed mutagenesis and homologous recombination. After their successful expression in 293T cells, we infected VSVΔG-Fluc*G pseudovirus, constructed four recombinant pseudoviruses and tested their effects on the cell force of infection.Results:Double digestion identification and sequence determination confirmed the successful construction of eukaryotic expression vectors pcDNA3.1 (+ )-Gc, pcDNA3.1 (+ )-Gc(N291Q), pcDNA3.1 (+ )-Gc(N352Q) and pcDNA3.1 (+ )-Gc(N374Q). Indirect immunofluorescence and Western Blotting result indicated the successful expression of all the four recombinant plasmids. SFTSV Gc recombinant pseudoviruses are specific for infecting Vero cells. Pseudovirus infection capacity was decreased significantly after the glycosylation site mutation, and the mutant strain with the glycosylation site at position 352 had the lowest level of infectivity ( P<0.001, P=0.001). Conclusions:The glycosylation site of SFTSV Gc may be associated with the infectious effect of the viral infection, and the amino acid mutation at position 352 has the greatest effect on the viral infectivity.
9.The effects of linalool on transient receptor potential vanilloid 1 pathway and its role in alleviating visceral hypersensitivity in rats with irritable bowel syndrome
Chong WANG ; Guohua LI ; Yin ZHU ; Xu SHU ; Youxiang CHEN
Chinese Journal of Digestion 2023;43(8):545-552
Objective:To observe the effects of linalool on central and alleviating peripheral nervous system through transient receptor potential vanilloid 1 (TRPV1) pathway and its role in alleviating visceral hypersensitivity in irritable bowel syndrome (IBS).Methods:Thirty-six female newborn Sprague-Dawley (SD) rat pups in specific pothogen free was selected, among which 30 rats were used for behavioral experiments and 6 rats for electrophysiological experiment. In behavioral experiments, 30 newborn SD rats were randomly divided into normal control group (0.2 mL 0.9% sodium chloride solution was injected into the colorectal), neonatal colonic inflammation (NCI) group (0.2 mL 0.5% acetic acid was injected into the colorectal), linalool 20, 50 and 100 mg/kg groups (after NCI model successfully established, the rat were gavaged with linalool 20, 50 or 100 mg/kg at 5 weeks old). At 6 weeks old, abdominal withdrawal reflex (AWR) and pressure value of pain threshold (inflation pressure value at AWR score of 3) was observed by colorectal distention test. One hour after behavioral experiments, the expression of TRPV1 at protein level in colonic mucosa and spinal cord of each group was detected by Western blotting and immunohistochemistry. In electrophysiological experiment, female SD rats aged 6 to 7 weeks were selected to make in vitro transverse sections of the spinal cord. Five to eight neurons were randomly selected from each rat for whole-cell patch-clamp recording. The effects of linalool, tetrodotoxin and anti capsaicinand on the spontaneous excitatory postsynaptic current (sEPSC) of substantiagelatinosa neurons was recorded. Independent sample t test and paired t test were used for statistical analysis. Results:The AWR score of rats in NCI group was higher than those in normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group at 40 mmHg (1 mmHg=0.133 kPa) pressure (2.5±0.2 vs. 1.0±0.3, 1.5±0.3, 1.5±0.2, and 1.5±0.2, respectively), at 60 mmHg pressure the AWR score was higher than those in normal control group, linalool 50 mg/kg group and linalool 100 mg/kg group (3.8±0.2 vs. 2.3±0.4, 2.3±0.5, and 2.0±0.3, respectively), and the differences were statistically significant ( t=4.39, 2.45, 3.16, 3.16, 3.31, 2.88 and 5.97; P=0.001, 0.034, 0.010, 0.010, 0.008, 0.028, and<0.001). The pain threshold of rats in NCI group was lower than those of normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group ((35.8±2.0) mmHg vs. (55.8±1.5), (49.2±2.4), (53.3±2.1), and (55.0±1.8) mmHg, respectively), and the differences were statistically significant ( t=-7.91, -4.28, -6.01, and -7.06; P<0.001, =0.002, <0.001, and <0.001). The results of Western blotting showed that the relative expression of TRPV1 at protein level in colorectal tissues of rats in NCI group was higher than those of normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group (0.86±0.03 vs. 0.32±0.03, 0.68±0.01, 0.45±0.03, and 0.56±0.02, respectively), and the relative expression of TRPV1 at protein level in spinal dorsal horn was higher than those of normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group (0.91±0.02 vs. 0.34±0.03, 0.72±0.03, 0.51±0.06, and 0.63±0.05), and the differences were statistically significant ( t=12.44, 5.14, 9.68, 7.69, 19.14, 5.13, 6.72, and 5.60; P<0.001, <0.001, <0.001, <0.001, <0.001, <0.001, =0.001, and <0.001). There were no statistically significant differences in the frequency and the outward current of sEPSC in neurons of same glial region among rats with 2 mmol/L linalool gavaged for 4 minutes, 0.5 μmol/L tetrodotoxin and 2 mmol/L linalool gavaged for 4 minutes ( n=5, (23.84±4.81) Hz vs. (20.54±5.71) Hz, (7.60±0.35) pA vs. (7.62±0.75) pA, both P>0.05). The frequency of sEPSC administered with 2 mmol/L linalool gavaged for 4 minutes was higher than that of neurons in the same glial area administered with 10 μmol/L capsazepine and 2 mmol/L linalool gavaged for 4 minutes ( n=5, (20.17±2.55) Hz vs.(14.09±2.98) Hz), and the difference was statistically significant ( t=3.58, P=0.021); however there was no statistically significant difference in the outward current ((7.42±0.78) pA vs. (7.03±1.32) pA, P>0.05). Conclusion:Linalool can relieve visceral hypersensitivity in IBS partially through TRPV1 pathway, which may be related to the hyperpolarization of the membrane potential of neurons in glial region.
10.Endoscopic submucosal dissection and gastrectomy for early gastric cancer: a Meta-Analysis
Chao ZHONG ; Jianyu YANG ; Qirui LI ; Qiang WANG ; Youxiang CHEN ; Guohua LI
China Journal of Endoscopy 2017;23(5):57-63
Objective To compare the difference of the effects and safety of endoscopic submucosal dissection (ESD) and surgery for early gastric cancer. Methods We searched the Pubmed, CBM, Embase, Cochrane Library, CNKI, CQVIP and WanFang data from January 1990 to June 2016 studies comparing endoscopic resection with gastrectomy for treatment of early gastric cancer. We selected the eligible studies according the including and excluding criteria. The quality of the included studies was assess using the Newcastle-Ottawa Scale (NOS), then using Revman 5.3 to make the Meta analysis. Result The meta-analysis enrolled 12 studies with 4331 patients, all of the studies were retrospectively analyzed. The result of the meta-analysis showed that there were no significant difference regarding the recurrence rate [(22/2586, 0.85%) vs (6/1134, 0.53%), P = 0.370] and five-year survival rate [(852/909, 93.72%) vs (707/746, 94.77%), P = 0.340] between endoscopic resection and gastrectomy. Gastrectomy was associated with higher en bloc resection rate, which were 100.00% and 92.23% respectively. However, gastrectomy was also related to longer operative time (SMD = -3.04, 95%CI: -3.64 ~ -2.45, P = 0.000) and hospital stay (SMD = -2.53, 95%CI: -3.73 ~ -1.32, P = 0.000). The postoperative complication was also higher than endoscopic, which were (45/816, 5.50%) vs (101/686, 14.72%) respectively. Conclusion There were no significant difference regarding recurrence rate and five-year survival rate between endoscopic and gastrectomy. While the en bloc resection rate was lower than gastrectomy, endoscopic offers a shorter hospital stay, shorter operative time with minimal invasive and fewer operating and postoperative complications than gastrectomy. Endoscopic should be recommended as a standard treatment for early gastric cancer with indications.

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