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.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Objective:To explore the application value of dynamic monitoring of serum thyroid hormone(THs)levels in assessing the condition changes and prognosis of elderly patients with sepsis.Methods:Using a retrospective cohort study,a total of 120 elderly critically ill patients hospitalized in the Department of Critical Care Medicine from April 2020 to April 2023 were selected as research subjects,divided into a sepsis group(60 cases)and a non-sepsis group(60 cases).Sepsis patients were further divided into a survival group(43 cases)and a death group(17 cases)based on 28-day survival status.Serum THs,PCT,IL-6,and Lac were measured on the 1st,5th,and 10th days of hospitalization(d1,d5,dl0)for sepsis patients,and the Sequential Organ Failure Assessment(SOFA)score and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score were recorded.The datas of non-sepsis patients were sampled on d1.The incidence of non-thyroidal illness syndrome(NTIS)was statistically analyzed,and the dynamic changes of serum THs among different groups were compared.The correlation between THs and disease severity,as well as the predictive value of THs for 28-day mortality in sepsis,was analyzed.Results:①The incidence of NTIS was 78.33％(94/120),with a significantly higher incidence in sepsis patients(96.67％,58/60)compared to non-sepsis patients(60.00％),with statistical significance(P＜0.05).②Compared to non-sepsis patients,sepsis patients had significantly lower levels of TSH,T3,FT3,and T4 on d1,while rT3 was significantly elevated,with statistical significance(P＜0.05);the difference in FT4 levels was not statistically significant(P＞0.05).Pearson correlation analysis showed that T3 and T4 were negatively correlated with SOFA and APACHE Ⅱ scores(P＜0.05),while other THs indicators showed no correlation with SOFA and APACHE Ⅱ scores(P＞0.05).ANOVA results indicated that there was no statistically significant difference in T4 levels at the three time points,and its changes showed no obvious linear trend over time(P＞0.05);T3 was significantly lower on d1 than on d5 and d10,and showed an increasing trend with longer hospitalization,while SOFA and APACHE Ⅱ scores were significantly higher on d1 than on d5 and d10,showing a decreasing trend with longer hospitalization(all P＜0.05).③Compared to the survival group of sepsis patients,the death group had significantly higher levels of PCT on d10,IL-6 on d5 and d10,and Lac on d1,d5,and d10(P＜0.05).The death group had significantly lower levels of T3 and T4 on d1,significantly lower levels of TSH,T3,T4,and FT4 on d5,and significantly lower levels of TSH,T3,FT3,T4,and FT4 on d10,with statistical significance(P＜0.05).④Logistic regression analysis showed that independent risk factors for 28-day mortality in sepsis patients included T3 on d1 and T3,FT3,T4,FT4,and IL-6 on d10,with statistical significance(P＜0.05).ROC curve analysis indicated that serum levels of T3,FT3,T4,and FT4 on d10 had certain predictive value for 28-day mortality in sepsis patients(all P＜0.05),with T3,FT3,and FT4 showing good predictive value,and their AUCs were 0.875,0.872,and 0.861,respectively.The combined AUC for predicting 28-day mortality in sepsis patients using T3,FT3,and FT4 on d10 increased to 0.902.Conclusion:The incidence of NTIS was high in elderly sepsis patients,and the serum THs levels and their dynamic changes were closely related to the patients'condition changes.Continuous dynamic monitoring of serum THs levels could help to assess the progression of sepsis,and T3 may serve as an indicator for evaluating the progression and prognosis of sepsis.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To investigate the effects of normal-high blood pressure and Grade 1 hypertension during early pregnancy on preeclampsia(PE)and adverse pregnancy outcomes in pregnant women.Methods A retrospective cohort study was conducted,enrolling 2,562 postpartum women who delivered at the Shiyan Maternal and Child Health Hospital from March 2020 to November 2023 as study participants.Prenatal examination data and delivery medical records were collected for analysis.Women were categorized into three groups based on blood pressure measurements taken before 20 weeks of gestation:normal blood pressure(n=2 029):systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg;normal high blood pressure(n=375):systolic blood pressure 120～139 mmHg or diastolic blood pressure 80～89 mmHg;and Level 1 hypertension(n=158):systolic blood pressure 140～159 mmHg or diastolic blood pressure 90～99 mmHg.The incidence rates of PE and adverse pregnancy outcomes(including cesarean section,placental abruption,spontaneous preterm delivery[before 37 weeks],postpartum hemorrhage,stillbirth after 20 weeks of gestation,Apgar score<7,neonatal admission to the NICU,small for gestational age,macrosomia,and neonatal death within 28 days of birth)were compared and analyzed across the three groups.Cox regression analysis was performed to investigate the impact of early pregnancy blood pressure levels on the risk of PE and adverse pregnancy outcomes.Results(1)Women with normal high blood pressure had a 2.163-fold increased risk of PE compared to women with normal blood pressure(95%CI:1.228～3.809,P=0.007).However,there were no statistically significant differences in the rates of cesarean section(OR=1.341,95%CI:0.528～3.405,P=0.537),placental abruption(OR=1.016,95%CI:0.925～1.115,P=0.740),Apgar score<7(OR=1.422,95%CI:0.976～2.071,P=0.066),spontaneous preterm birth(OR=1.027,95%CI:0.925～1.140,P=0.617),postpartum bleeding(OR=1.141,95%CI:0.873～1.491,P=0.334),stillbirth after 20 weeks of gestation(OR=1.276,95%CI:0.980～1.661,P=0.070),neonatal admission to NICU(OR=1.301,95%CI:0.674～2.511,P=0.432),small for gestational age(OR=1.089,95%CI:0.927～1.279,P=0.299),macrosomia(OR=1.336,95%CI:0.824～2.166,P=0.240),or neonatal death within 28 days of birth(OR=1.275,95%CI:0.918～1.770,P=0.147).(2)Compared to women with normal blood pressure,women with grade 1 hypertension had a significantly higher risk of preeclampsia(OR=3.829,95%CI:1.749～8.385,P<0.001),cesarean section(OR=2.414,95%CI:1.298～4.489,P=0.005),and placental abruption(OR=2.537,95%CI:1.196～5.384,P=0.015).Additionally,they had a higher rate of Apgar score<7(OR=1.829,95%CI:1.069～3.130,P=0.027).No statistically significant differences were observed for spontaneous preterm birth(OR=1.404,95%CI:0.713～2.764,P=0.326),postpartum bleeding(OR=1.236,95%CI:0.845～1.807,P=0.274),stillbirth after 20 weeks of gestation(OR=1.076,95%CI:0.902～1.283,P=0.415),neonatal admission to NICU(OR=1.346,95%CI:0.873～2.075,P=0.178),small for gestational age(OR=1.417,95%CI:0.926～2.168,P=0.108),macrosomia(OR=1.235,95%CI:0.629～2.424,P=0.539),or neonatal death within 28 days of birth(OR=1.275,95%CI:0.918～1.770,P=0.147).(3)ROC analysis shows that when the sample combination was normal high blood pressure(n=375),the predictive/evaluative efficacy AUC of early pregnancy blood pressure values(threshold 139/89)for PE was 0.757.When the sample combination was level 1 hypertension(n=158),the predictive/evaluative efficacy AUC of early pregnancy blood pressure values(threshold 159/99)for four adverse outcomes,including PE,cesarean section,placental abruption,and Asperger's score<7,were 0.789,0.717,0.709,and 0.742,respectively.Conclusion Compared with pregnant and parturient women with normal blood pressure,having a normal high blood pressure or grade 1 hypertension before 20 weeks of pregnancy will significantly increase the risk of PE;in addition,grade 1 hypertension is also associated with a higher incidence of adverse pregnancy outcomes,including cesarean section,placental abruption,and low Apgar score of the newborn.

Objective To investigate the feasibility and safety of bedside transesophageal echocardiography(TEE)-guided atrial septostomy in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods Eight patients(2 females and 6 males)who developed pulmonary edema during VA-ECMO treatment between January 2020 and October 2024 were enrolled.All patients underwent bedside TEE-guided atrial septal puncture,followed by gradual balloon dilation using an Inoue balloon(diameter:18-24 mm).The endpoint for dilation was defined as mean left atrial pressure＜15 mmHg.Post-procedure evaluation included assessment of the septal defect size,mean left atrial pressure,and improvement in bilateral pulmonary edema.Results The mean age of all 8 patients was(43.50±16.84)years old.Atrial septostomy was successfully performed in all patients.The mean balloon dilation diameter was(22.75±2.68)mm,resulting in a mean septal defect size of(6.31±0.37)mm.The mean left atrial pressure significantly decreased from(26.63±1.77)mmHg pre-procedure to(12.75±1.28)mmHg post-procedure(P＜0.001).All patients demonstrated marked improvement in bilateral pulmonary edema,and six patients also showed a significant reduction in the severity of mitral regurgitation following the procedure.No procedure-related complications were observed.Conclusions Bedside TEE-guided atrial septostomy is safe and effective for reducing left heart loading during ECMO support and improving pulmonary edema.

AIM To investigate the ameliorative effects of Compound Fufangteng Mixture(CFM)on cyclophosphamide(CTX)-induced immunosuppression in mice.METHODS Forty-eight male C57BL/6J mice were randomly divided into the blank control group,the model group,the levamisole hydrochloride group(40 mg/kg)and the low-dose,medium-dose and high-dose CFM groups(3.75,7.5,10 g/kg),with 8 mice in each group,and given respective intervention orally once daily for 14 days.On the 5th to 7th day of administration,with the blank control group given normal saline intraperitoneally,the other groups underwent intraperitoneal CTX injections(80 mg/kg).24 hours after the last administration,organ indices of thymus and spleen were calculated;splenic histopathological alterations were assessed by HE staining;serum levels of IL-2,IL-6 and IgG were quantified using ELISA;splenic CD4+,CD8+T lymphocytes,alongside CD86+and CD206+macrophages populations were analyzed by flow cytometry;and splenic expression of CD4,CD8 and F4/80 was evaluated by immunohistochemical staining.RESULTS In CTX-treated mice,CFM administration mitigated body weight loss;enhanced thymus weight and thymic index;ameliorated splenic immune cell populations,elevated serum levels of cytokines IL-2,IL-6 and IgG in serum;and upregulated splenic levels of CD45+CD3+T lymphocytes and F4/80+CD11b+macrophages,alongside increasing the expression of CD4,CD8 and F4/80 surface markers.CONCLUSION CFM alleviates CTX-induced immunosuppression state in mice by modulating immune cells,restoring immune function and enhancing anti-inflammatory and tissue repair capabilities.

Objective To investigate the feasibility and safety of bedside transesophageal echocardiography(TEE)-guided atrial septostomy in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods Eight patients(2 females and 6 males)who developed pulmonary edema during VA-ECMO treatment between January 2020 and October 2024 were enrolled.All patients underwent bedside TEE-guided atrial septal puncture,followed by gradual balloon dilation using an Inoue balloon(diameter:18-24 mm).The endpoint for dilation was defined as mean left atrial pressure＜15 mmHg.Post-procedure evaluation included assessment of the septal defect size,mean left atrial pressure,and improvement in bilateral pulmonary edema.Results The mean age of all 8 patients was(43.50±16.84)years old.Atrial septostomy was successfully performed in all patients.The mean balloon dilation diameter was(22.75±2.68)mm,resulting in a mean septal defect size of(6.31±0.37)mm.The mean left atrial pressure significantly decreased from(26.63±1.77)mmHg pre-procedure to(12.75±1.28)mmHg post-procedure(P＜0.001).All patients demonstrated marked improvement in bilateral pulmonary edema,and six patients also showed a significant reduction in the severity of mitral regurgitation following the procedure.No procedure-related complications were observed.Conclusions Bedside TEE-guided atrial septostomy is safe and effective for reducing left heart loading during ECMO support and improving pulmonary edema.

Objective To investigate the short-term efficacy of 3D-printed artificial vertebral body combined with PEEK-Cage implantation in anterior cervical surgery for ossification of the posterior longitudinal ligament of the cervical spine(OPLL).Methods The clinical data of 15 patients with OPLL who underwent anterior cervical surgery with 3D-printed artificial vertebral body and PEEK-Cage implantation in the Fifth Department of Orthopaedics,Liaoning Provincial People's Hospital from September 2022 to June 2023 was retrospectively analyzed.The surgical time,intraoperative blood loss,postoperative drainage volume,bed rest time,hospital stay,and surgery-related complications of patients were analyzed.The Japanese Orthopaedic Association(JOA)score and visual analogue scale(VAS)score of patients were counted before surgery,3 days after surgery,1 month after surgery and 6 months after surgery.The changes of Cobb angle of fusion segment of patients were recorded before surgery,3 days after surgery,1 month after surgery and 6 months after surgery.Results All 15 patients successfully completed the surgery.The surgical time was 130 to 160 minutes,with an average of(148.68±10.04)minutes.The intraoperative blood loss was 50 to 200 mL,with an average of(130.0±18.8)mL.The postoperative drainage volume was 220 to 980 mL,with an average of(270.0±24.6)mL.The bed rest time was 3 to 11 days,with an average of(3.6±2.8)days.The hospital stay was 7 to 16 days,with an average of(8.2±2.6)days.All patients'incisions healed in the first stage,and no infection occurred.One patient suffered from dural sac tear during surgery;4 patients had dysphagia after surgery;1 patient suffered from muscle weakness of one limb after surgery;Hematoma formed in the incision of cervical spine in 1 patient 3 days after surgery.At 3 days,1 month,and 6 months after surgery,the Cobb angle,VAS score and JOA score of 3 patients with myeloid symptoms and upper limb root pain were significantly improved compared with those before surgery(P<0.05),and the Cobb angle and JOA score of 12 patients with only myeloid symptoms were significantly improved compared with those before surgery(P<0.05).Conclusion 3D-printed artificial vertebral body combined with PEEK-Cage implantation in anterior cervical surgery is an effective method for the treatment of OPLL,which can significantly relieve patients'pain and improve their dysfunction in a short time,with good stability and fusion effect.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.