Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective To analyze the clinical characteristics of patients with coronary heart disease complicated by gastrointestinal hemorrhage and explore the independent prognostic factors.Methods The clinical data of patients with coronary heart disease complicated by gastrointestinal hemorrhage who were treated in the department of emergency of the First Affiliated Hospital of Zhejiang University School of Medicine from January 1,2022 to December 31,2023 were collected,including general information:gender,age,smoking history,drinking history,gastrointestinal hemorrhage-related symptoms(hematemesis,melena,hematochezia,hematemesis combined with melena)or positive fecal occult blood test,past medical history[hypertension,diabetes,atrial fibrillation,liver cirrhosis,malignancy,prior gastrointestinal hemorrhage],coronary heart disease treatment history(history of coronary stent implantation,history of coronary artery bypass grafting),history of antithrombotic drugs,vital signs on admission[body temperature,pulse rate,systolic blood pressure,pulse oxygen saturation(SpO2)],laboratory tests[random blood glucose,white blood cell count(WBC),hemoglobin(Hb),platelet count(PLT),C-reactive protein(CRP),serum creatinine(SCr),blood urea nitrogen(BUN),serum albumin(Alb),alanine aminotransferase(ALT),aspartate aminotransferase(AST),MB isoenzyme of creatine kinase(CK-MB),troponin I(TNI),brain natriuretic peptide(BNP),fibrinogen(Fib),prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer,ejection fraction(EF)],treatment process[gastrointestinal hemorrhage management(gastrointestinal endoscopy examination or treatment,vascular interventional therapy),blood transfusion volume(red blood cells,plasma),ICU admission rate and admission time,hospital stay],the causes of gastrointestinal hemorrhage comprehensively inferred from imaging and gastrointestinal endoscopy.According to the treatment outcome,the patients were divided into the cured group and the death group,and the differences in clinical data between the two groups were compared.Multivariate Logistic regression analysis was used to identify the independent influencing factors of death outcome.The receiver operating characteristic(ROC)curves were plotted to compare the predictive value of each factor for prognosis.Results A total of 526 patients were enrolled,including 486 in the cured group and 40 in the death group.The causes of death were multiple organ dysfunction syndrome(22 cases),acute myocardial infarction(7 cases),malignant arrhythmia(2 cases),respiratory failure(2 cases),infection(2 cases),hemorrhagic shock(3 cases),acute cerebral infarction(1 case),and cerebral hemorrhage(1 case).No statistically significant differences were found between the two groups in terms of gender,age,smoking history,excessive drinking history,symptoms(hematemesis,hematochezia,positive fecal occult blood test,hematemesis combined with melena),past medical history(hypertension,atrial fibrillation,liver cirrhosis,tumor history,prior gastrointestinal hemorrhage),coronary heart disease treatment history,antithrombotic drug history,body temperature,pulse rate,SpO2,random blood glucose,WBC,Hb,PLT,ALT,AST,CK-MB,TNI,Fib,APTT,EF,gastrointestinal hemorrhage management,causes of gastrointestinal hemorrhage,red blood cell/plasma transfusion volume,and hospital stay(all P>0.05).Compared with the cured group,the death group had a lower rate of melena as the initial symptom,systolic blood pressure,and serum Alb level[melena rate:32.50%(13/40)vs.66.26%(322/486),systolic blood pressure(mmHg,1 mmHg≈0.133 kPa):104.71±8.52 vs.122.52±22.59,Alb(g/L):30.80(27.60,33.70)vs.34.70(32.65,39.05),all P<0.05],and a higher prevalence of diabetes,higher levels of CRP,SCr,BUN,BNP,PT,D-dimer,a higher ICU admission rate,and a longer ICU stay[diabetes prevalence:70.00%(28/40)vs.29.42%(143/486),CRP(mg/L):94.91(30.69,125.56)vs.2.95(1.17,24.31),SCr(μmol/L):200.0(123.0,407.0)vs.82.5(66.8,112.0),BUN(mmol/L):15.81(14.00,22.21)vs.7.61(5.00,14.49),BNP(ng/L):2 970.50(1 504.25,6 193.50)vs.442.00(141.25,1 590.25),PT(s):13.50(12.60,22.50)vs.12.25(11.58,13.30),D-dimer(μg/L):5601(4115,11352)vs.609(267,1350),ICU admission rate:67.50%(27/40)vs.6.99%(34/486),ICU stay(days):3(2,16)vs.0(0,0),all P<0.05].With clinical outcomes(death,cure)as the dependent variable,variables with statistical significance in univariate analysis were included in the multivariate Logistic regression analysis.The results showed that systolic blood pressure and serum Alb were independent protective factors for death outcome[odds ratio(OR)=0.960,0.818;95%confidence interval(95%CI)was 0.933-0.987,0.719-0.932;P=0.004,0.002;respectively],while CRP and SCr were independent risk factors for death outcome[OR=1.013,1.004;95%CI was 1.006-1.020,1.002-1.006,all P<0.001].Taking death outcome as the state variable and serum Alb,systolic blood pressure,SCr,and CRP as the test variables respectively,the ROC curves were plotted.The results indicated that serum Alb,systolic blood pressure,SCr,CRP and their combined detection all had high predictive efficacy for the death outcome[area under the curve(AUC)=0.825,0.775,0.862,0.819,0.928;95%CI was 0.766-0.885,0.729-0.820,0.818-0.905,0.703-0.934,0.891-0.965;sensitivity was 78.6%,92.8%,85.7%,85.7%,92.9%;specificity was 72.7%,72.5%,78.8%,83.8%,77.8%,all P<0.001].The combined detection of the 4 factors had the highest predictive efficacy(all P<0.05).Conclusions Systolic blood pressure,serum Alb,CRP,and SCr were independent influencing factors for the in-hospital death outcome of patients with coronary heart disease complicated by gastrointestinal hemorrhage.The Logistic regression model constructed based on these factors had better predictive efficacy for death outcome than single factor analysis.

Objective To analyze the clinical characteristics of patients with coronary heart disease complicated by gastrointestinal hemorrhage and explore the independent prognostic factors.Methods The clinical data of patients with coronary heart disease complicated by gastrointestinal hemorrhage who were treated in the department of emergency of the First Affiliated Hospital of Zhejiang University School of Medicine from January 1,2022 to December 31,2023 were collected,including general information:gender,age,smoking history,drinking history,gastrointestinal hemorrhage-related symptoms(hematemesis,melena,hematochezia,hematemesis combined with melena)or positive fecal occult blood test,past medical history[hypertension,diabetes,atrial fibrillation,liver cirrhosis,malignancy,prior gastrointestinal hemorrhage],coronary heart disease treatment history(history of coronary stent implantation,history of coronary artery bypass grafting),history of antithrombotic drugs,vital signs on admission[body temperature,pulse rate,systolic blood pressure,pulse oxygen saturation(SpO2)],laboratory tests[random blood glucose,white blood cell count(WBC),hemoglobin(Hb),platelet count(PLT),C-reactive protein(CRP),serum creatinine(SCr),blood urea nitrogen(BUN),serum albumin(Alb),alanine aminotransferase(ALT),aspartate aminotransferase(AST),MB isoenzyme of creatine kinase(CK-MB),troponin I(TNI),brain natriuretic peptide(BNP),fibrinogen(Fib),prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer,ejection fraction(EF)],treatment process[gastrointestinal hemorrhage management(gastrointestinal endoscopy examination or treatment,vascular interventional therapy),blood transfusion volume(red blood cells,plasma),ICU admission rate and admission time,hospital stay],the causes of gastrointestinal hemorrhage comprehensively inferred from imaging and gastrointestinal endoscopy.According to the treatment outcome,the patients were divided into the cured group and the death group,and the differences in clinical data between the two groups were compared.Multivariate Logistic regression analysis was used to identify the independent influencing factors of death outcome.The receiver operating characteristic(ROC)curves were plotted to compare the predictive value of each factor for prognosis.Results A total of 526 patients were enrolled,including 486 in the cured group and 40 in the death group.The causes of death were multiple organ dysfunction syndrome(22 cases),acute myocardial infarction(7 cases),malignant arrhythmia(2 cases),respiratory failure(2 cases),infection(2 cases),hemorrhagic shock(3 cases),acute cerebral infarction(1 case),and cerebral hemorrhage(1 case).No statistically significant differences were found between the two groups in terms of gender,age,smoking history,excessive drinking history,symptoms(hematemesis,hematochezia,positive fecal occult blood test,hematemesis combined with melena),past medical history(hypertension,atrial fibrillation,liver cirrhosis,tumor history,prior gastrointestinal hemorrhage),coronary heart disease treatment history,antithrombotic drug history,body temperature,pulse rate,SpO2,random blood glucose,WBC,Hb,PLT,ALT,AST,CK-MB,TNI,Fib,APTT,EF,gastrointestinal hemorrhage management,causes of gastrointestinal hemorrhage,red blood cell/plasma transfusion volume,and hospital stay(all P>0.05).Compared with the cured group,the death group had a lower rate of melena as the initial symptom,systolic blood pressure,and serum Alb level[melena rate:32.50%(13/40)vs.66.26%(322/486),systolic blood pressure(mmHg,1 mmHg≈0.133 kPa):104.71±8.52 vs.122.52±22.59,Alb(g/L):30.80(27.60,33.70)vs.34.70(32.65,39.05),all P<0.05],and a higher prevalence of diabetes,higher levels of CRP,SCr,BUN,BNP,PT,D-dimer,a higher ICU admission rate,and a longer ICU stay[diabetes prevalence:70.00%(28/40)vs.29.42%(143/486),CRP(mg/L):94.91(30.69,125.56)vs.2.95(1.17,24.31),SCr(μmol/L):200.0(123.0,407.0)vs.82.5(66.8,112.0),BUN(mmol/L):15.81(14.00,22.21)vs.7.61(5.00,14.49),BNP(ng/L):2 970.50(1 504.25,6 193.50)vs.442.00(141.25,1 590.25),PT(s):13.50(12.60,22.50)vs.12.25(11.58,13.30),D-dimer(μg/L):5601(4115,11352)vs.609(267,1350),ICU admission rate:67.50%(27/40)vs.6.99%(34/486),ICU stay(days):3(2,16)vs.0(0,0),all P<0.05].With clinical outcomes(death,cure)as the dependent variable,variables with statistical significance in univariate analysis were included in the multivariate Logistic regression analysis.The results showed that systolic blood pressure and serum Alb were independent protective factors for death outcome[odds ratio(OR)=0.960,0.818;95%confidence interval(95%CI)was 0.933-0.987,0.719-0.932;P=0.004,0.002;respectively],while CRP and SCr were independent risk factors for death outcome[OR=1.013,1.004;95%CI was 1.006-1.020,1.002-1.006,all P<0.001].Taking death outcome as the state variable and serum Alb,systolic blood pressure,SCr,and CRP as the test variables respectively,the ROC curves were plotted.The results indicated that serum Alb,systolic blood pressure,SCr,CRP and their combined detection all had high predictive efficacy for the death outcome[area under the curve(AUC)=0.825,0.775,0.862,0.819,0.928;95%CI was 0.766-0.885,0.729-0.820,0.818-0.905,0.703-0.934,0.891-0.965;sensitivity was 78.6%,92.8%,85.7%,85.7%,92.9%;specificity was 72.7%,72.5%,78.8%,83.8%,77.8%,all P<0.001].The combined detection of the 4 factors had the highest predictive efficacy(all P<0.05).Conclusions Systolic blood pressure,serum Alb,CRP,and SCr were independent influencing factors for the in-hospital death outcome of patients with coronary heart disease complicated by gastrointestinal hemorrhage.The Logistic regression model constructed based on these factors had better predictive efficacy for death outcome than single factor analysis.

The superior mesenteric artery (SMA) is one of the visceral branches of the abdominal aorta. It has multiple branches to supply blood and nutrition to the intestinal segment, and these form an anastomosis with each other. SMA injuries are usually classified as major visceral artery injuries, and have an incidence of <1%. The clinical manifestations of patients with SMA injuries include intra-abdominal bleeding and peritoneal irritation. The compromised blood supply can lead to intestinal ischemia and perforation. These injuries are often not diagnosed in time and have significant mortality rates of 25%‍-‍68% due to the lack of specific features (Maithel et al., 2020). Not only that, but patients with less severe trauma or no visible damage on initial examination may still have clinically significant intra-abdominal injuries (Nishijima et al., 2012). Emergency departments often encounter multiple cases that require urgent diagnosis and treatment (Li et al., 2021; Zhang et al., 2021; Zhou et al., 2021), and therefore, it is imperative to diagnose and manage these rare injuries expeditiously.
Humans ; Mesenteric Artery, Superior/surgery* ; Abdominal Injuries/diagnosis* ; Intestines

Objective To assess the value of prenatal ultrasonography on fetal forearm and crus malformations by studying the ultrasonographic characteristic in relation to methods of examination. Methods All fetus were evaluated by using a systematic continuous sequence approach (SCSA) with ultrasonography. A close attention was paid on shapes, structures and movement of fetal forearm and crus, and fetus specimens after induced labor were rescanned by ultrasonography under the condition of mimic intra-uterus. Results Thirty of 33 cases (90.9%) with fetal forearm and crus malformations (totally 48 of 54 limb anormalies, 88.9%) were correctly diagnosed by prenatal ultrasonography. Six limb malformations of 3 cases were missed. Conclusion Our study demonstrates that the malformations of forearm and crus detected with prenatal ultrasonography are highly accordant with the malformations revealed in fetus in vitro. It is important to abide by the SCSA in ultrasonographic diagnosis of fetal forearm and crus malformation.