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.

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.

Portal hypertensive biliopathy is a secondary condition of intrahepatic and extrahepatic bile duct abnormalities caused by portal hypertension, especially in extrahepatic portal venous obstruction. Most patients may remain asymptomatic for a long time, while a few may present with symptomatic portal hypertensive biliopathy, such as obstructive jaundice, cholelithiasis with or without cholangitis, gastrointestinal bleeding, and others. Such disease is rare in clinical practice and is prone to misdiagnosis and missed diagnosis. Improper treatment can lead to serious adverse consequences. We report a case of unexpected discovery of bile duct dilation due to abdominal pain, which was ultimately diagnosed as portal hypertensive biliopathy based on the medical history, manifestations of portal hypertension, and imaging examinations, especially intraductal ultrasonography.

Objective:To analyze the relationship between blood urea nitrogen (BUN)/albumin (ALB) ratio (B/A) and prognosis of patients undergoing percutaneous coronary intervention (PCI) guided by ultrasound before operation.Methods:A total of 116 patients who underwent PCI under the guidance of intra-coronary ultrasound in Xianyang Central Hospital from February 2020 to December 2022 were retrospectively selected as the observation group, and 120 healthy people in the same period were selected as the control group. All patients were followed up for 1 year after surgery, and 116 patients were divided into poor prognosis group ( n=33) and good prognosis group ( n=83), taking major adverse cardiovascular events (MACE) as the end point during follow-up. The levels of BUN and ALB in peripheral blood of all subjects were detected after admission, and B/A was calculated. The basic data, biochemical indexes and B/A of each group were analyzed and compared. The predictive value of preoperative BUN, ALB and B/A on postoperative MACE in patients with PCI guided by intra-coronary ultrasound was analyzed by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was used to evaluate the related influencing factors of postoperative MACE in patients with PCI guided by intra-coronary ultrasound. Results:The left ventricular end-diastolic inner diameter (LVEDD), N-terminal B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme (CK-MB), BUN and B/A in the observation group were higher than those in the control group, and left ventricular ejection fraction (LVEF) and ALB were lower than those in the control group (all P<0.05). NT-proBNP, CK-MB, BUN and B/A in the poor prognosis group were higher than those in the good prognosis group, and LVEF and ALB were lower than those in the good prognosis group (all P<0.05). ROC curve results showed that the AUC of peripheral blood BUN, ALB and B/A predicting postoperative MACE in patients with PCI guided by intra-coronary ultrasound were 0.833(95% CI: 0.783-0.883), 0.859(95% CI: 0.809-0.909) and 0.922(95% CI: 0.872-0.972). Multivariate logistic regression analysis showed that LVEF [ OR(95% CI)=1.952(1.317-2.895)], NT-proBNP [ OR(95% CI)=2.625(1.643-4.193)], BUN [ OR(95% CI)=3.353(1.922-5.851)], ALB [ OR(95% CI)=3.792(2.049-7.018)] and B/A [ OR(95% CI)=3.277(2.000-5.370)] were all the influencing factors of postoperative MACE in patients undergoing PCI guided by intra-coronary ultrasound ( P<0.05). Conclusions:The level of B/A in patients with PCI guided by intra-coronary ultrasound increased before surgery, and the high level of B/A is a risk factor for postoperative MACE, which can be used as a biological index to evaluate the postoperative MACE in patients with PCI guided by intra-coronary ultrasound.

Objective:To analyze the relationship between blood urea nitrogen (BUN)/albumin (ALB) ratio (B/A) and prognosis of patients undergoing percutaneous coronary intervention (PCI) guided by ultrasound before operation.Methods:A total of 116 patients who underwent PCI under the guidance of intra-coronary ultrasound in Xianyang Central Hospital from February 2020 to December 2022 were retrospectively selected as the observation group, and 120 healthy people in the same period were selected as the control group. All patients were followed up for 1 year after surgery, and 116 patients were divided into poor prognosis group ( n=33) and good prognosis group ( n=83), taking major adverse cardiovascular events (MACE) as the end point during follow-up. The levels of BUN and ALB in peripheral blood of all subjects were detected after admission, and B/A was calculated. The basic data, biochemical indexes and B/A of each group were analyzed and compared. The predictive value of preoperative BUN, ALB and B/A on postoperative MACE in patients with PCI guided by intra-coronary ultrasound was analyzed by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was used to evaluate the related influencing factors of postoperative MACE in patients with PCI guided by intra-coronary ultrasound. Results:The left ventricular end-diastolic inner diameter (LVEDD), N-terminal B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme (CK-MB), BUN and B/A in the observation group were higher than those in the control group, and left ventricular ejection fraction (LVEF) and ALB were lower than those in the control group (all P<0.05). NT-proBNP, CK-MB, BUN and B/A in the poor prognosis group were higher than those in the good prognosis group, and LVEF and ALB were lower than those in the good prognosis group (all P<0.05). ROC curve results showed that the AUC of peripheral blood BUN, ALB and B/A predicting postoperative MACE in patients with PCI guided by intra-coronary ultrasound were 0.833(95% CI: 0.783-0.883), 0.859(95% CI: 0.809-0.909) and 0.922(95% CI: 0.872-0.972). Multivariate logistic regression analysis showed that LVEF [ OR(95% CI)=1.952(1.317-2.895)], NT-proBNP [ OR(95% CI)=2.625(1.643-4.193)], BUN [ OR(95% CI)=3.353(1.922-5.851)], ALB [ OR(95% CI)=3.792(2.049-7.018)] and B/A [ OR(95% CI)=3.277(2.000-5.370)] were all the influencing factors of postoperative MACE in patients undergoing PCI guided by intra-coronary ultrasound ( P<0.05). Conclusions:The level of B/A in patients with PCI guided by intra-coronary ultrasound increased before surgery, and the high level of B/A is a risk factor for postoperative MACE, which can be used as a biological index to evaluate the postoperative MACE in patients with PCI guided by intra-coronary ultrasound.

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.

Portal hypertensive biliopathy is a secondary condition of intrahepatic and extrahepatic bile duct abnormalities caused by portal hypertension, especially in extrahepatic portal venous obstruction. Most patients may remain asymptomatic for a long time, while a few may present with symptomatic portal hypertensive biliopathy, such as obstructive jaundice, cholelithiasis with or without cholangitis, gastrointestinal bleeding, and others. Such disease is rare in clinical practice and is prone to misdiagnosis and missed diagnosis. Improper treatment can lead to serious adverse consequences. We report a case of unexpected discovery of bile duct dilation due to abdominal pain, which was ultimately diagnosed as portal hypertensive biliopathy based on the medical history, manifestations of portal hypertension, and imaging examinations, especially intraductal ultrasonography.

Sjogren's syndrome is a chronic inflammatory autoimmune disease characterized by invasion of exocrine glands such as lacrimal gland and salivary gland and high lymphocyte infiltration. Interstitial cystitis is a chronic cystitis disease with frequent micturition, urgency, nocturia and/or pelvic pain as its main clinical manifestations, and its pathological changes are bladder submucosal ulcer and fibrosis as its main manifestations. Sjogren's syndrome complicated with interstitial cystitis is not uncommon. Anti-muscarinic type 3 acetylcholine receptor (M3R) antibody will not only cause gland dysfunction, but also play an important role in the pathogenesis of interstitial cystitis. The pathogenesis may include: ①Immune inflammation accompanied by mast cells and neurogenic inflammation with up-regulation of bladder sensory nerve. ②The detrusor contraction function is impaired, which induces ATP release and stimulates sensory nerve outflow.

Due to the virtues of no stutter peaks, low rates of mutation, and short amplicon sizes, insertion/deletion (InDel) polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications (Wang et al., 2021). Herein, a self-developed panel of 43 InDel loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing (HCB) including 301 random healthy individuals. The lengths of amplicons at 43 InDel loci in this panel ranged from 87 to 199 bp, which indicated that the panel could be used as an effective tool to utilize highly degraded DNA samples for human identity testing. The loci in this panel were validated and performed well for forensic degraded DNA samples (Jin et al., 2021). The combined discrimination power (PD) and combined probability of exclusion (PE) values in this panel indicated that the 43 InDel loci could be used as the candidate markers in personal identification and parentage testing of HCB. In addition, population genetic relationships between the HCB and 26 reference populations from five continents based on 19 overlapped InDel loci were displayed by constructing a phylogenetic tree, principal component analysis (PCA), and population genetic structure analysis. The results illustrated that the HCB had closer genetic relationships with the Han populations from Chinese different regions.
Beijing ; China ; Forensic Genetics/methods* ; Gene Frequency ; Genetics, Population ; Humans ; INDEL Mutation ; Phylogeny

The clinical data of a case with late-onset isolated sulfite oxidase deficiency(ISOD)admitted in the Department of Neurology, Children′s Hospital, Zhejiang University School of Medicine in July 2021 were retrospectively analyzed.Fifteen previously published cases of late-onset ISOD were also reviewed.The patient was a girl, who was hospitalized because of " motor regression with mental retardation for 5 days" at 1 year old.The manifestations of the patient were extrapyramidal symptoms, regression of motor development and seizures.The level of urinary sulfites in the patient was increased.Magnetic resonance imaging (MRI) features were bilateral pallidus and substantia nigra.Gene sequencing suggested a pure missense mutation of the sulfite oxidase( SUOX) gene c. 650(exon5)G>A(p.Arg217Gln). In 16 cases of late-onset ISOD, the median age at onset and diagnosis was 10.5 months and 34.0 months, respectively.The common clinical manifestations were hypotonia (13 cases), seizures (10 cases), movement disorders (9 cases), and ectopia lentis (6 cases). The most common brain MRI feature was pallidus changes (11 cases), followed by lesions of substantia nigra (5 cases), and cerebral atrophy (4 cases). Fourteen cases of late-onset ISOD showed a positive urinary sulfite test.The missense mutation of the SUOX gene was found in 9 cases.It suggested that brain MRI involvement of bilateral pallidus, high excretion of urine sulfites and the missense mutation of the SUOX gene were important diagnostic clues for late-onset ISOD.