Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides

Objective:To investigate the effect of ultra-early enteral nutrition (UEEN) support on the prognosis of young and middle-aged postoperative patients with cerebral hemorrhage.Methods:The clinical data of young and middle-aged patients (aged 18-59 years) admitted to Tianjin Fifth Central Hospital from January 2020 to June 2023 after surgery for intracerebral hemorrhage were retrospectively analyzed, and the general data, nutritional indexes, gastrointestinal complications, neurological function recovery and long-term prognosis of the patients were recorded. According to the time of initiation of enteral nutrition (EN) support, patients were divided into UEEN group (EN implementation within 12 hour after surgery) and early enteral nutrition (EEN) group (EN implementation within 24 to 48 hour after surgery). The differences of the above indexes between the two groups were analyzed and compared.Results:A total of 64 young and middle-aged postoperative patients with cerebral hemorrhage were enrolled, including 32 cases in the UEEN group and 32 cases in the EEN group. There were no significant differences in gender, age, proportion of hypertension and diabetes, Glasgow coma score (GCS) on admission and surgical methods between the two groups. In terms of nutritional indexes, serum total protein, albumin and hemoglobin levels of patients in both groups on day 7 after admission were lower than those on day 1, and higher than those on day 3, and the above indexes levels in UEEN group were significantly higher than those in EEN group on day 7 [total protein (g/L): 63.05±5.79 vs. 59.02±6.63, albumin (g/L): 40.40±5.26 vs. 37.66±4.63, hemoglobin (g/L): 133.33±12.58 vs. 123.80±22.12, all P < 0.05]. In terms of gastrointestinal complications, the incidence of stress ulcer in the UEEN group within 14 days after admission was significantly lower than that in the EEN group [12.5% (4/32) vs. 31.3% (10/32), P < 0.05], but there was no statistically significant difference in feeding intolerance symptoms between the two groups. In terms of neurological recovery and long-term prognosis, GCS scores and Barthel index scores of 14 days after admission were higher than those of 1 day after admission, but there was no statistical significance between the two groups. Six months after surgery, Glasgow outcome scale (GOS) and Barthel index score of the UEEN group were significantly higher than those of the EEN group (GOS score: 3.81±1.06 vs. 3.18±1.07, Barthel index score: 60.78±7.24 vs. 54.52±5.13, both P < 0.05). Conclusion:UEEN support can improve the nutritional level of young and middle-aged postoperative patients with cerebral hemorrhage, reduce the occurrence of postoperative gastrointestinal complications, promote the recovery of neurological function, and improve the long-term prognosis.

The incidence of falls, as well as the consequent fear of falling among aged hemodialysis patients, is notably high. Such fear contributes to both psychosomatic damage and a diminished quality of life, constituting a significant risk factor for mortality in this demographic. This article comprehensively reviews the overview of fear of falling in aged hemodialysis patients, its effects on these individuals, the current prevalence, influencing factors, and intervention measures. It aims to provide a scientific foundation for formulating effective strategies to counteract the fear of falling in aged hemodialysis patients.

Objective: To understand the current situation of suicidal ideation among middle school students in Taiyuan City and its correlation with exposure to social ecological risk factors, so as to provide a reference basis for exploring the causes of suicidal ideation among middle and high school students and formulating effective preventive measures. Methods: A questionnaire survey was conducted among 2 639 middle school students in urban and rural areas of Taiyuan City by multistage stratified random cluster sampling, including general demography characteristics, social ecological risk factors and suicidal ideation. SPSS 26.0 software was used for Chi squared test and binary Logistic regression analysis. Results: The overall detection rate of suicidal ideation was 24.7 %. There were statistically significant differences in the detection rate of suicidal ideation among middle school students in different gender, grade, family residence, maternal education level, perceived family economic conditions, number of close friends, self-perceived academic burden ( χ 2=38.17, 13.44, 10.77, 8.15, 19.76, 18.95, 59.75, P <0.05). After adjusting the general demography characteristics, the binary Logistic regression showed that moderate and high risk in the individual, family and cultural dimension, and high risk in the school dimension of the social ecology were all positively correlated with suicidal ideation among middle school students ( OR=1.38, 2.28, 1.97, 3.28, 1.48, 2.15, 1.71, P <0.05). Conclusion The suicidal ideation among middle school students is related to individuals, families, and schools in the social ecological microsystem, as well as the cultural environment in the macro system. It is necessary to conduct intervention in suicidal ideation at the individual, family, and school levels, meanwhile, strengthening social and cultural construction to reduce the impact of adverse factors on the mental health among adolescents.

Purpose: This study aimed to compare mortality rates after discharge between the patients with non-ST-elevation myocardial infarction (NSTEMI) and those with ST-elevation myocardial infarction (STEMI), and identify each mortality risk factors in these two types of myocardial infarction. Materials and Methods: Between 2011 and 2015, 13105 consecutive patients were enrolled in the Korea Acute Myocardial Infarction-National Institute of Health registry (KAMIR-NIH); 12271 patients with acute myocardial infarction met the inclusion criteria and were further stratified into the STEMI (n=5828) and NSTEMI (n=6443) groups. The occurrence of mortality and cardiac mortality at 3 years were compared between groups, and the factors associated with mortality for NSTEMI and STEMI were evaluated. Results: The comparison between these two groups and long-term follow-up outcomes showed that the cumulative rates of allcause and cardiac mortality were higher in the NSTEMI group than in the STEMI group [all-cause mortality: 10.9% vs. 5.8%; hazards ratio (HR), 0.464; 95% confidence interval (CI), 0.359–0.600, p<0.001; cardiac mortality: 6.6% vs. 3.5%, HR, 0.474; 95% CI, 0.344–0.654, p<0.001, respectively). In the NSTEMI group, low left ventricular ejection fraction (LVEF; <40%), no percutaneous coronary intervention (PCI), old age (≥65 years), and low hemoglobin level (<12 g/dL) were identified as risk factors for 3-year mortality. In the STEMI group, old age, low glomerular filtration rate (<60 mL/min/1.73 m2 ), low LVEF, high heart rate (>100 beats/min), no PCI, and low hemoglobin level were identified as the risk factors for 3-year mortality. Conclusion The NSTEMI group had higher mortality compared to the STEMI group during the 3-year clinical follow-up after discharge. Low LVEF and no PCI were the main risk factors for mortality in the NSTEMI group. In contrast, old age and renal dysfunction were the risk factors for long-term mortality in the STEMI group.

Purpose: This study aimed to compare mortality rates after discharge between the patients with non-ST-elevation myocardial infarction (NSTEMI) and those with ST-elevation myocardial infarction (STEMI), and identify each mortality risk factors in these two types of myocardial infarction. Materials and Methods: Between 2011 and 2015, 13105 consecutive patients were enrolled in the Korea Acute Myocardial Infarction-National Institute of Health registry (KAMIR-NIH); 12271 patients with acute myocardial infarction met the inclusion criteria and were further stratified into the STEMI (n=5828) and NSTEMI (n=6443) groups. The occurrence of mortality and cardiac mortality at 3 years were compared between groups, and the factors associated with mortality for NSTEMI and STEMI were evaluated. Results: The comparison between these two groups and long-term follow-up outcomes showed that the cumulative rates of allcause and cardiac mortality were higher in the NSTEMI group than in the STEMI group [all-cause mortality: 10.9% vs. 5.8%; hazards ratio (HR), 0.464; 95% confidence interval (CI), 0.359–0.600, p<0.001; cardiac mortality: 6.6% vs. 3.5%, HR, 0.474; 95% CI, 0.344–0.654, p<0.001, respectively). In the NSTEMI group, low left ventricular ejection fraction (LVEF; <40%), no percutaneous coronary intervention (PCI), old age (≥65 years), and low hemoglobin level (<12 g/dL) were identified as risk factors for 3-year mortality. In the STEMI group, old age, low glomerular filtration rate (<60 mL/min/1.73 m2 ), low LVEF, high heart rate (>100 beats/min), no PCI, and low hemoglobin level were identified as the risk factors for 3-year mortality. Conclusion The NSTEMI group had higher mortality compared to the STEMI group during the 3-year clinical follow-up after discharge. Low LVEF and no PCI were the main risk factors for mortality in the NSTEMI group. In contrast, old age and renal dysfunction were the risk factors for long-term mortality in the STEMI group.

Glomerular filtration rate (GFR) is an important indicator of renal failure. However, regarding delta GFR in acute myocardial infarction (AMI) is rare. In this study, it was examined whether the delta GFR had an adverse effect on outcomes in patients with AMI and multivessel disease (MVD). Among 13,105 consecutive patients enrolled in the Korea Acute Myocardial Infarction–National Institute of Health registry, 2619 with AMI and MVD who underwent percutaneous cardiac intervention (PCI) were assigned to the better delta GFR (group I, n=1432 [54.7%]) or worse delta GFR (group II, n=1187 [45.3%]) groups and followed for 3 or more years. The mean age of group I was lower than that of group II (62.64±11.52 years vs. 64.29±11.64 years; p<0.001). On multivariate analysis, delta GFR (hazard ratio, 1.50; 95% confidence interval, 1.05-2.13; p=0.024) was a negative risk factor for adverse cardiac events. Age over 65 years (p< 0.001), history of MI (p=0.008), low hemoglobin (p<0.001), high triglyceride (p=0.008), low high-density lipoprotein cholesterol (p=0.002), and low left ventricular ejection fraction (LVEF) (p<0.001) were prognostic factors for major adverse cardiac events (MACE). In patients with a GFR <60 mL/min/1.73 m2, mortality was increased by 0.9% in the multivessel PCI group and 0.7% in the IRA-only PCI group at the 1-year follow-up. According to the 3-year clinical follow-up analysis, prognosis was better in better delta GFR patients with AMI and MVD who underwent PCI than in worse delta GFR patients.