Objective:To explore the clinical phenotype and genetic characteristics of a Chinese Han pedigree with Darier′s disease(DD).Methods:A DD pedigree, who visited Tongji Hospital of Tongji University on October 22, 2023, was selected as the study subject. Clinical data of the pedigree were collected, and whole-genome exom sequencing was performed on the proband. Suspected variant loci were screened, and Sanger sequencing was used to validate the variant in pedigree members. Bioinformatics analysis was performed on the variant loci. This study was approved by the Medical Ethics Committee of Tongji Hospital of Tongji University(Ethics No.K-W-2024-004).Results:① The proband is a 67-year-old female with clinical features of DD, such as keratotic papules in sebaceous areas. ② Whole-genome exom sequencing revealed a missense variant, c. 68G>A (p.Gly23Glu), in the exon 1 of ATP2A2 gene of the proband. Sanger sequencing showed that the proband′s eldest daughter also carried this variant. This variant was not detected in other pedigree members, indicating a co-segregation of the variant with the disease phenotype in the pedigree. ③ According to the interpretation principles of gene variants by the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PS1+ PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusions:The c. 68G>A (p.Gly23Glu) variant in the ATP2A2 gene may be the genetic cause of the disease in this pedigree. This finding further enriches the genetic variant spectrum in DD patients and provides a basis for clinical diagnosis and genetic counseling for patients.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a Chinese Han pedigree with Darier's disease (DD). METHODS: A DD pedigree, who visited Tongji Hospital of Tongji University on October 22, 2023, was selected as the study subject. Clinical data of the pedigree were collected, and whole exome sequencing was performed on the proband. Suspected variant loci were screened, and Sanger sequencing was used to validate the variant in pedigree members. Bioinformatics analysis was performed on the variant loci. This study was approved by the Medical Ethics Committee of Tongji Hospital of Tongji University Ethics No.K-W-2024-004). RESULTS: The proband is a 67-year-old female with clinical features of DD, such as keratotic papules in sebaceous areas. whole exome sequencing revealed a missense variant, c.68G>A (p.Gly23Glu), in the exon 1 of ATP2A2 gene of the proband. Sanger sequencing showed that the proband's eldest daughter also carried this variant. This variant was not detected in other pedigree members, indicating a co-segregation of the variant with the disease phenotype in the pedigree. According to the interpretation principles of gene variants by the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PS1+PM1+PM2_Supporting+PP1+PP3+PP4). CONCLUSION The c.68G>A (p.Gly23Glu) variant in the ATP2A2 gene may be the genetic cause of the disease in this pedigree. This finding further enriches the genetic variant spectrum in DD patients and provides a basis for clinical diagnosis and genetic counseling for patients.
Aged ; Female ; Humans ; Male ; China ; Darier Disease/genetics* ; Exome Sequencing ; Mutation, Missense ; Pedigree ; Phenotype ; East Asian People ; Sarcoplasmic Reticulum Calcium-Transporting ATPases

Objective:To explore the clinical phenotype and genetic characteristics of a Chinese Han pedigree with Darier′s disease(DD).Methods:A DD pedigree, who visited Tongji Hospital of Tongji University on October 22, 2023, was selected as the study subject. Clinical data of the pedigree were collected, and whole-genome exom sequencing was performed on the proband. Suspected variant loci were screened, and Sanger sequencing was used to validate the variant in pedigree members. Bioinformatics analysis was performed on the variant loci. This study was approved by the Medical Ethics Committee of Tongji Hospital of Tongji University(Ethics No.K-W-2024-004).Results:① The proband is a 67-year-old female with clinical features of DD, such as keratotic papules in sebaceous areas. ② Whole-genome exom sequencing revealed a missense variant, c. 68G>A (p.Gly23Glu), in the exon 1 of ATP2A2 gene of the proband. Sanger sequencing showed that the proband′s eldest daughter also carried this variant. This variant was not detected in other pedigree members, indicating a co-segregation of the variant with the disease phenotype in the pedigree. ③ According to the interpretation principles of gene variants by the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PS1+ PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusions:The c. 68G>A (p.Gly23Glu) variant in the ATP2A2 gene may be the genetic cause of the disease in this pedigree. This finding further enriches the genetic variant spectrum in DD patients and provides a basis for clinical diagnosis and genetic counseling for patients.

BACKGROUND: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. METHODS: Mice with scleroderma received a single 50 lg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. RESULTS: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. CONCLUSION We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycininduced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

Objectives:To establish a grading model on prognosis of drug-coated balloon (DCB) treatment on femoropopliteal de novo lesions, and assess whether patients at high risk could benefit from combination of directional atherectomy(DA).Methods:The clinical data of 114 patients with femoropopliteal de novo lesions admitted to Department of Vascular Surgery, Peking University People′s Hospital from October 2015 to January 2019 were collected retrospectively. There were 95 patients(108 limbs) underwent DCB treatment, including 66 males and 29 females, aged 71.9 years old(range:48 to 91 years), and 19 patients (21 limbs) underwent DA combined with DCB treatment, including 13 males and 6 females, aged 69.5 years old(range: 62 to 80 years). The demographic data, intraoperative and postoperative conditions of the patients were collected. Cox regression model was performed for modeling and then goodness of fit was tested. Kaplan-Meier estimate was carried out between the two groups for patients at high risk and low risk, respectively.Results:All patients were followed up for more than 24 months. Restenosis occurred on 34 limbs in DCB group and 3 limbs in DA+DCB group. Severe calcification( HR=3.804, 95% CI:2.460 to 5.883), popliteal artery involvement ( HR=2.104, 95% CI:1.368 to 3.236), long lesion ( HR=1.824, 95% CI:1.196 to 2.780), poor runoff( HR=1.736, 95% CI:1.025 to 2.940), chronic kidney disease( HR=1.601, 95% CI:1.040 to 2.463) were independent risk factors of restenosis after DCB treatment, and were defined 3, 2, 1, 1 and 1 points, respectively. Total points≥3 was regarded as high risk group. Kaplan-Meier analysis showed that patients in low risk group did not benefit from DA+DCB comparing with DCB with regard to primary patency at 24 months (77.78% vs. 90.31%, P=0.271) while patients benefited from DA+DCB comparing with DCB in high risk group(88.26% vs. 20.80%, P<0.01). Conclusions:The grading model shows satisfying clinical value. The clinical effect of DA+DCB is better than DCB along in high risk group. Patients at high risk are supposed to receive aggressive vessel preparation like DA.

Objectives:To establish a grading model on prognosis of drug-coated balloon (DCB) treatment on femoropopliteal de novo lesions, and assess whether patients at high risk could benefit from combination of directional atherectomy(DA).Methods:The clinical data of 114 patients with femoropopliteal de novo lesions admitted to Department of Vascular Surgery, Peking University People′s Hospital from October 2015 to January 2019 were collected retrospectively. There were 95 patients(108 limbs) underwent DCB treatment, including 66 males and 29 females, aged 71.9 years old(range:48 to 91 years), and 19 patients (21 limbs) underwent DA combined with DCB treatment, including 13 males and 6 females, aged 69.5 years old(range: 62 to 80 years). The demographic data, intraoperative and postoperative conditions of the patients were collected. Cox regression model was performed for modeling and then goodness of fit was tested. Kaplan-Meier estimate was carried out between the two groups for patients at high risk and low risk, respectively.Results:All patients were followed up for more than 24 months. Restenosis occurred on 34 limbs in DCB group and 3 limbs in DA+DCB group. Severe calcification( HR=3.804, 95% CI:2.460 to 5.883), popliteal artery involvement ( HR=2.104, 95% CI:1.368 to 3.236), long lesion ( HR=1.824, 95% CI:1.196 to 2.780), poor runoff( HR=1.736, 95% CI:1.025 to 2.940), chronic kidney disease( HR=1.601, 95% CI:1.040 to 2.463) were independent risk factors of restenosis after DCB treatment, and were defined 3, 2, 1, 1 and 1 points, respectively. Total points≥3 was regarded as high risk group. Kaplan-Meier analysis showed that patients in low risk group did not benefit from DA+DCB comparing with DCB with regard to primary patency at 24 months (77.78% vs. 90.31%, P=0.271) while patients benefited from DA+DCB comparing with DCB in high risk group(88.26% vs. 20.80%, P<0.01). Conclusions:The grading model shows satisfying clinical value. The clinical effect of DA+DCB is better than DCB along in high risk group. Patients at high risk are supposed to receive aggressive vessel preparation like DA.

Objective:To compare the early diagnostic value of the indicators of endothelial injury, renal injury, inflammation and coagulation in patients with sepsis-induced acute kidney injury (AKI).Methods:A retrospective study was performed on 119 patients with sepsis from February 2017 to March 2018. Lab tests were performed on patients at admission, which included:ing soluble thrombomodulin (sTM), tissue plasminogen activators and inhibitors (t-PAI-C), antithrombin III (AT-III), thrombin-antithrombin (TAT) complex, plasmin-alpha 2, plasmin inhibitor complex (PIC), fibrin degradation product (FDP), fibrinogen (FIB), D-Dimer, prothrombin time (PT), prothrombin time international normalized ratio (PT-INR), procalcitoni (PCT), white blood cell (WBC), neutrophil (Neu), and platelet count (PLT). The receiver-operating characteristic curve was used to analyze the predictive value of the above indicators, and logistic regression analysis was used to analyze the risk factors of sepsis-induced AKI. A prospective study was conducted from April 2018 to September 2018 and 46 patients were enrolled. The lab tests results retrieved including sTM, t-PAI-C, FDP, AT-III, TAT, PIC, FIB, D-Dimer, PT, PCT, serum cystatin C (Cys C), urine albumin (microalbumin) and albumin to creatinine ratio (ACR), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary N-acetyl-beta-glucosaminidase (uNAG), and urinary retinol-binding protein (uRBP). As same with the previous group, the receiver-operating characteristic curve was used to analyze the diagnostic value of the above indicators, and logistic regression Was used to analyze the risk factors of sepsis-induced AKI.Results:(1) In the retrospective study: sTM, D-Dimer, PCT, PT, and PT-INR were statistically different. sTM, D-Dimer, PCT, PT, and PT-INR had a good diagnostic value for septis-induced AKI, among which, sTM had a highest diagnostic value (AUC: 0.857; 95% CI: 0.790, 0.924), better sensitivity (64.4%) and specificity (91.8%). The high expression of sTM and history of chronic kidney disease were independent risk factors for septis-induced AKI.(2) In the prospective study: PCT, sTM , Cys C, and uNGAL were statistically different. PCT, sTM, Cys C, uNGAL showed good predictive features for septis-induced AKI. sTM had the highest sensitivity (>0.999) while uNGAL had the highest specificity (0.800). The high expression of sTM was an independent risk factor for septis-induced AKI. Conclusions:sTM and uNGAL represent endothelial injury and renal tubular injury respectively. sTM is an independent risk factor of sepsis-induced AKI.

Objective To evaluate the mid-and long-term results of chimney-endovascular aneurysm repair (Ch-EVAR) on efficacy and durability.Methods Data of abdominal aortic aneurysm (AAA) patients receiving Ch-EVAR were retrospectively collected and analyzed.Results From Jan 2011 to Dec 2016,21 patients received Ch-EVAR in our institution including 18 males and 3 females with the average age 74.0 ±6.31 years.One patient died and 20 patients were followed up for an mean period of 53.2 months.During EVAR procedures 14 patients received left renal artery chimney stents,6 patients had right renal artery chimney stents and one did bilateral renal artery chimney stents.Technical success was achieved in all patients (100％).Differences between preoperative and one-week postoperative value of serum creatinine (P =0.639) and estimated glomerular filtration rate (eGFR) (P =0.804) showed no statistical difference.The differences of maximum sac diameter between preoperiation (60.1 ± 13.1 mm) and follow-up (59.2 ± 13.5 mm) was not significant (P =0.826).Six patients died during follow-up and none was aortic events related.All chimney stents were patent.One patient developed late type Ⅱ endoleak and refused reintervention regardless of aneurysm expansion.Conclusion For short hostile neck AAA patients with considerable surgical risk Ch-EVAR may be an effective and durable alternative.

Objective To evaluate thoracic endovascular repair (TEAVR) techniques for the treatment of Stanford type A aortic dissection.Methods From Jan 2010 to Dec 2016,68 cases (male 51,female 17,age 58 ± 9 years) of Stanford type A aortic dissection were treated by endovascular stent grafting.Results Aortic stents were delivered and deployed successfully in all target arteries.48 important aortic arch arteries were reconstructed (brachiocephalic trunk 6,left carotid commond artery 18,left subclavian artery 24).30-day mortality rate was 5.9％ (4/68).Endoleak developed in 13 cases and new stroke in 2 cases.Average follow-up time was 6-112 months.One death occurred after 6-months postoperatively for multiple organ failure.2 cases were new endoleak and 1 case was left upper limb ischemia.Up to the most recent review or death,the false lumen remained thrombosed in all cases.Conclusions Optimized endovascular stent-graft treatment is effective method to treat Stanford type A aortic dissection.

Objective To analyze the long-term curative effect of radical surgery for Budd-Chiari syndrome and the postoperative recurrence risk factors.Method Clinical data of 83 patients treated with radical surgery for Budd-Chiari syndrome through exposure of the entire inferior vena cava of the hepatic segment at Peking University People's Hospital between Jul 2001 and Dec 2010 was studied.Survival rate,patency rate of the inferior vena cava and hepatic vein,and risk factors were analyzed.Results There were 5 perioperative deaths with a mortality rate of 6％.Child-Pugh C liver function (P =0.001) was independently related to the perioperative death.The mean follow-up time was 84 ± 35 (60-173)months.There were 8 patients (10.3％) lost to follow-up.10 patients (12.8％) died during follow-up.Child-Pugh C liver function (P =0.003) was independently related to the follow-up death.24 cases (40％) suffered from recurrence with inferior vena cava restenosis in 12 cases (20％),that of hepatic vein in 2 cases (3.3％),and 10 cases (16.7％)with both inferior vena cava and hepatic vein restenosis.Membranous lesion of inferior vena cava (P =0.004) and inadequate anticoagulation time (P =0.004) were independently related to the recrudescence.Conclusions Long term recurrence of Budd-Chiari syndrome after radical surgery through exposure of the entire inferior vena cava of the hepatic segment is related to membranous lesion of inferior vena cava and inadequate anticoagulation time.