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.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

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 understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.Methods:From January 2017 to March 2022,151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study,microcolumn gel card test was used for irregular antibody screening,and antibody specificity identification was further performed in some antibody-positive subjects.Results:The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91％(1 375/151 471),0.23％(355/151 471)was detected in the first trimester,0.05％(71/151 471)in the second trimester,and 0.63％(949/151 471)in the third trimester.The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester,and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester.The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11％(689/1 375),which was the highest,the suspicious positive was 18.69％(257/1 375),and the positive was 31.20％(429/1 375).The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group,however,in the third trimester,the proportion of suspicious positive and weakly positive was lower than the first trimester,while,the proportion of positive was higher than the first trimester,and the difference was statistically significant(P＜0.001).Among the irregular antibody screening positive pregnant women,the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy≤1.Among 60 pregnant women who underwent antibody identification,the distributions of the antibodies were as follows:Rh blood group system accounted for 23.33％(14/60),Lewis system 43.33％(26/60),Kidd system 3.33％(2/60),MNS system 16.67％(10/60),P1PK system 1.67％(1/60),autoantibodies 1.67％(1/60),and 4 cases was unable to identify(6.67％,4/60).Among specific antibodies,the anti-Lea was the most common(30.00％),followed by anti-E(16.67％)and anti-M(16.67％).Conclusion:The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds,understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.

Objective:To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area,and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion.Methods:The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method,and 48 122 males in the same period were taken as controls.The data were analyzed by Chi-square test.Results:There were 112 870 cases(99.64％)of RhD+in 113 283 samples.In RhD+cases,CCDee(48.39％)and CcDEe(32.88％)were the main phenotypes.The first case of D--phenotype in Chongqing area was detected.413 cases(0.36％)of RhD-were detected,with ccdee(52.78％)and Ccdee(33.41％)as the main phenotypes.Compared with RhD-group,RhD+group showed statistically significant difference in Rh phenotype distribution(P＜0.01).Among 65 161 maternal samples,the positive rate of 5 antigens of Rh blood group from high to low was D＞e＞C＞c＞E,and there was no significant difference compared with male samples(P＞0.05).There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women,as well as between pregnant/postpartum women with different ABO blood groups(P＞0.05).In pregnant and postpartum women,there was no significant difference in distribution of Rh phenotype among the normal pregnancy population,the population with adverse pregnancy history,the population using human assisted reproductive technology(ART)and the population with infertility(P＞0.05).There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors(P＞0.05).In RhD positive pregnant and postpartum women,the probability of finding compatible blood for CcDEe phenotype was 100％,the probability of finding compatible blood for CCDee,CcDee and CCDEe phenotypes was 45％-60％,the probability of finding compatible blood for ccDEE,ccDEe and CcDEE phenotypes was 5％-10％,and the probability of finding compatible blood for other phenotypes was lower than 0.5％.The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99％of patients.Conclusion:Rh phenotype detection should be carried out for pregnant and postpartum women,and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.

Objective:To evaluate the clinical efficacy of Xiaozheng Granules(XZG)combined with Jingqiankang Bacterio-static Gelatin(JBG)on chronic prostatitis of the damp-heat and blood-stasis type based on infrared thermography(IRT).Methods:This study included 120 cases of chronic prostatitis with damp-heat and blood stasis treated in the First Affiliated Hospital of Henan U-niversity of Chinese Medicine with oral XZG(the control group,n=60)or oral XZG combined with anal administration of JBG(the trial group,n=60),both for 4 weeks.We obtained the NIH-CPSI and traditional Chinese medicine(TCM)syndrome scores of the patients,measured the temperatures in the belt-vessel,lower focal and inguinal regions by IRT before and after treatment,recorded the adverse reactions during the treatment,and compared them between the two groups of patients.Results:Compared with the base-line,the NIH-CPSI and TCM syndrome scores were significantly decreased in the two groups of patients after treatment(P<0.05),even more significantly in the trial than in the control group(P<0.05),and after 1 hour of treatment,the temperatures in the Xia-jiao([34.09±0.34]vs[33.60±0.40]℃,P<0.05)and the groin region([34.49±0.28]vs[33.78±0.30]℃,P<0.05)were remarkably reduced in the trial group,but showed no significant change in the control group(Xiajiao region:[34.02±0.29]vs[34.05±0.26]℃,P>0.05;groin region:[34.54±0.25]vs[34.51±0.22]℃,P>0.05).After 4 weeks of treatment,the temperatures in the Xiajiao and groin regions were even lower in the trial([33.13±0.41]℃ and[33.21±0.29]℃ )and the control group([33.42±0.25]℃ and[33.86±0.29]℃ )than the baseline and those after 1 hour of treatment(P<0.05),and still more significantly in the former than in the latter group(P<0.05).The total effectiveness rate was markedly higher in the trial group than in the control(88.14％ vs 77.19％,P<0.05),and no obvious adverse reactions were observed in neither group.Conclusion:XZG combined with JBG is a safe and effective treatment of chronic prostatitis with damp-heat and blood-stasis,which can significantly reduce the NIH-CPSI and TCM syndrome scores and IRT temperatures in the lower focal and in-guinal regions of the patients.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease(CHD)in offspring.Methods The parents of children with simple CHD aged 0 to 1 year(n=683)were recruited as the case group,while the parents of healthy children aged 0 to 1 year(n=740)served as the control group.A case-control study was conducted,and a questionnaire was used to collect information on perinatal exposures.After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching,the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined,as well as the cumulative effects of smoking and drinking on CHD risk.Results Maternal active smoking(OR=2.91,95%CI:1.60-5.30),passive smoking(OR=1.94,95%CI:1.56-2.42),and alcohol consumption(OR=2.59,95%CI:1.89-3.54),as well as paternal smoking(OR=1.52;95%CI:1.22-1.90)and drinking(OR=1.48,95%CI:1.19-1.84),were associated with an increased risk of CHD in offspring.There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring(P>0.05).The more parents'smoking and drinking behaviors during the perinatal pregnancy,the higher the risk of CHD in their offspring(OR=1.50,95%CI:1.36-1.65).Conclusions Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring,and there is a cumulative effect on CHD risk,suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.