A Frequent Observation of Wolff-Parkinson-White Syndrome and Fasciculoventricular Pathways in Patients With Danon Disease.

BACKGROUND: Danon disease is typically associated with cardiomyopathy and ventricular pre-excitation. The study aimed to characterize the clinical profile of Danon disease, analyze electrocardiographic (ECG) and electrophysiologic features, and investigate their association with Wolff-Parkinson-White (WPW) syndrome and fasciculoventricular pathways (FVPs).Methods and Results:Clinical course, family history, ECG and electrophysiological data were collected from 16 patients with Danon disease. Over 0.4-8 years of follow up, 1 female patient died suddenly, and 5 male patients died of progressive heart failure by age 13-20 years. Family history analysis revealed that 3 mothers experienced hospitalization or death for heart failure at age 28-41 years. There was 100% penetrance for ECG abnormalities in 13 patients with original ECGs. Short PR intervals and delta waves were present in 9 and 8 patients, respectively. There were significant age-associated increases in the QRS complex width (r=0.556, P=0.048) and the number of leads with notched QRS (r=0.575, P=0.04). Four patients who underwent electrophysiological studies all had FVPs, and 2 of them still had left-side atrioventricular pathways. CONCLUSIONS: Danon disease causes a malignant clinical course characterized by early death caused by heart failure in both genders and progressive ECG changes as patients age. The pre-excited ECG pattern is related to FVPs and WPW, which is suggestive of extensive cardiac involvement.

Large wounds reconstruction of the lower extremity with combined latissimus dorsi musculocutaneous flap and flow-through anterolateral thigh perforator flap transfer.

BACKGROUND: Management of large wounds of the lower extremities remains a challenge for plastic and reconstructive surgeons. Herein, a surgical technique and clinical algorithm using the combined transfer of a latissimus dorsi (LD) musculocutaneous flap and flow-through anterolateral thigh (ALT) perforator flap for the treatment of extensive soft-tissue defects is described. METHODS: From January 2012 to September 2018, 12 patients (six men and six women) aged 6-37 years, sustained injuries in road traffic accidents with large soft-tissue defects in the lower extremities. Seven cases were Gustillo Anderson type IIIB open fractures and two cases were Gustillo Anderson type IIIC open fractures. Two wounds were located in the knee joint, four in the calf, and six in the ankle and foot. The skin defect size ranged from 25 × 20 cm2 to 36 × 25 cm2 . All patients in this series underwent reconstruction using combined transfer of the LD musculocutaneous flap and flow-through ALT perforator flap, wherein the LD was attached through its pedicle to the distal continuation of the ALT flap. RESULTS: The size of the flow-through ALT perforator flaps ranged from 13.5 × 6.5 cm2 to 31 × 8.5 cm2 . The size of the LD musculocutaneous skin paddle ranged from 25 × 6 cm2 to 34 × 7 cm2 , and that of the muscle paddle ranged from 13 × 3.5 cm2 to 30 × 11 cm2 . One patient experienced postoperative thrombosis of the venous pedicle, and the flap was salvaged after emergency re-exploration and thrombectomy. No other complications were observed postoperatively. The mean follow-up period was 26.8 months. All patients were able to ambulate independently at the end of the follow-up period. CONCLUSIONS: The combined transfer of the LD musculocutaneous flap and flow-through ALT perforator flap ensured adequate surface coverage, making it a feasible procedure for large soft-tissue defects.

Versatile design of compound vastus lateralis muscle and anterolateral thigh musculocutaneous perforator free flaps for customized reconstruction of complex skin and soft tissue defects in the extremities.

BACKGROUND: Compound anterolateral thigh flaps are popular for three-dimensional reconstruction of complex soft tissue defects. We present our 10-year experience using compound vastus lateralis (VL) muscle and anterolateral thigh musculocutaneous perforator (ALTP) flaps, and introduce three versatile customizations of this flap for individualized reconstruction of complex three-dimensional soft tissue defects. METHODS: From May 2008 to June 2017, compound VL muscle and ALTP flaps were performed in 67 consecutive patients aged 14-75 years (62 men and 5 women). The defects were in either the lower (n = 53) or upper extremity (n = 14), and ranged in size from 8 × 4 cm2 to 25 × 6 cm2. Dead space volume ranged from 4 × 2 × 1 cm3 to 20 × 3 × 2 cm3, and all flaps were harvested from patients' thighs as one of three types. In type A, a single perforator supplied both the skin and muscle components, with the vascular bundle penetrating the muscle component. In type B, a single perforator supplied both skin and muscle components with separate branches to the skin and muscle. In type C, separate vessels supplied the skin and muscle. RESULTS: In the 67 patients, 65 flaps survived, and the donor site was closed directly. Vascular compromise occurred in four patients on the first postoperative day. Two flaps were salvaged after emergency re-exploration. Flap loss occurred in two patients, and these defects were repaired using other flaps. The follow-up period ranged from 8 to 60 months (mean, 11.9 months). All flaps had satisfactory appearance and texture, and no patients experienced limited hip and knee joint mobility from the donor site operation. CONCLUSIONS: Compound VL muscle and ALTP flaps are a reliable option to reconstruct complex defects of the extremities. Identifying three flap types allowed for more precise customization to cover complex defects with limited donor site morbidity.

A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia.

BACKGROUND: Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders. METHODS: The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction. RESULTS: We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM. CONCLUSIONS: A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.

Catheter-Based Computed Tomography Angiography in Anterolateral Thigh Perforator Mapping of Chinese Patients.

BACKGROUND: During reconstructive surgery, anterolateral thigh (ALT) flap harvest is challenging due to variation and uncertainty in perforator distribution. We performed a pilot study to identify the predictive value of catheter-based computed tomography angiography (C-CTA) and traditional CTA (T-CTA) in ALT perforator mapping for patients whose ALT perforators were difficult to identify. METHODS: Thirty-four consecutive T-CTA/C-CTA-mapped ALT flaps were evaluated for extremity reconstruction. The perforator location, origin, and course were compared between T-CTA/C-CTA imaging and intraoperative findings. The mapping efficiency of T-CTA and C-CTA was compared thoroughly. RESULTS: Among the 34 ALT thigh flaps, 117 (36) of the 130 perforators identified intraoperatively were visible on C-CTA (T-CTA) in a subgroup of Chinese limb trauma patients with limited activity. C-CTA showed a satisfactory efficiency in perforator mapping, which was much better than the efficiency of T-CTA. C-CTA also showed a much better sensitivity (90.00 vs. 27.69%), specificity (94.74 vs. 66.67%), and accuracy (91.07 vs. 36.69%), and a much lower false-positive (1.68 vs. 26.53%), and false-negative rate (10.00 vs. 72.31%). Moreover, C-CTA could accurately predict the origin and septocutaneous or intramuscular course in all identified perforators. All flaps were elevated successfully and survived. CONCLUSION: C-CTA outperforms T-CTA in the preoperative perforator mapping of ALT flaps in a subgroup of Chinese limb trauma patients. C-CTA should be the method of choice for perforator mapping in patients whose ALT flaps are intended for extremity reconstruction.

Associations between circulating full-length angiopoietin-like protein 8 levels and severity of coronary artery disease in Chinese non-diabetic patients: a case-control study.

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8), which is a novel hormone produced in liver and adipose tissue, is involved in regulating lipid metabolism. Patients with diabetes and coronary artery disease (CAD) have remarkably higher levels of ANGPTL8 than those with only diabetes. However, no studies have investigated the involvement of ANGPTL8 in CAD in Chinese non-diabetic individuals. Therefore, we investigated full-length circulating ANGPTL8 levels in patients with CAD and the association between ANGPT8 levels and severity of CAD in Chinese individuals without diabetes. METHODS: We performed a case-control study in 149 Chinese non-diabetic subjects, including 80 patients with CAD and 69 controls. The Gensini stenosis scoring system was used to assess the severity of CAD. Circulating full-length ANGPTL8 levels were measured by an enzyme-linked immunosorbent assay kit. The associations between circulating full-length ANGPTL8 levels and CAD were determined by multivariate logistic regression analysis. The association between ANGPTL8 levels and Gensini scores was determined by multivariate linear regression analysis. RESULTS: Circulating full-length ANGPTL8 levels were significantly higher in Chinese non-diabetic patients with CAD compared with controls (665.90 ± 243.49 vs 462.27 ± 151.85 pg/ml, P < 0.001). After adjusting for confounding factors, we found that circulating full-length ANGPTL8 levels were an independent risk factor for CAD (odds ratio = 2.002/100 pg ANGPTL8, 95% CI 1.430-2.803, P < 0.001) and circulating ANGPTL8 levels were positively associated with the Gensini score (ß = 5.701/100 pg ANGPTL8, 95% CI 1.306-10.096, P = 0.012). CONCLUSIONS: This study shows that the circulating ANGPTL8 levels are significantly increased in patients with CAD compared with controls in Chinese non-diabetic individuals. Circulating full-length ANGPTL8 levels are an independent risk factor for CAD and they are positively associated with the severity of CAD. Trial registration This study was registered in the Chinese Clinical Trial Registry (No. ChiCTR-COC-17010792).

SYNTAX Score-II Predicts Long-Term Mortality in Patients Who Underwent Left Main Percutaneous Coronary Intervention Treated With Second-Generation Drug-Eluting Stents.

The aim of this study was to evaluate the capacity of the SYNTAX Score-II (SS-II) to predict long-term mortality in patients undergoing left main percutaneous coronary intervention (LM-PCI) treated with second-generation drug-eluting stents (DES).Data from 487 consecutive patients with de novo left main coronary artery disease undergoing PCI were retrospectively studied. The patients were divided into tertiles according to the SS-II: low SS-II tertile (SS-II ≤ 22), intermediate SS-II tertile (SS-II of 23 to 30), and high SS-II tertile (SS-II ≥ 30). The survival curves were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the possible associations between the SS-II and the rates of long-term mortality. The predictive ability of the SS-II for mortality was assessed and compared with the SYNTAX score (SS) alone by an area under the receiver operator curve (AUC).The overall SS-II was 27.3 ± 9.1. At a mean follow-up of 5.1 years, the long-term mortality was 6.0%. The rates of mortality were 2.4%, 3.4%, and 11.6%, respectively (P < 0.0001) in the low, intermediate, and high SS-II tertiles. The cardiac mortality rates were 1.8%, 1.4%, and 8.1%, respectively (P = 0.002) among patients in the 3 groups. By multivariate analysis, SS-II was an independent predictor of the long-term mortality (hazard ratio: 1.56, 95% confidence interval: 1.05 to 2.32; P = 0.03). The AUC demonstrated a substantially higher predictive accuracy of the SS-II for mortality compared with the SS alone (AUC was 0.689 and 0.596, respectively).In patients with LM-PCI treated with a second-generation DES, the SS-II is an independent predictor of long-term mortality and demonstrates a superior predictability compared with the SS alone.

Synthesis and biological evaluation of novel pyrazoline derivatives as potent anti-inflammatory agents.

Twenty-eight pyrazoline derivatives, which originated from pyranochalcones, have been synthesized and evaluated for their inhibitory potency on the production of inflammatory mediator nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Among them, three compounds (1c, 11c, and 15c) exhibited potent inhibitory effects on NO production and iNOS activity superior to positive control Indomethacin, with 1c being most efficacious. Furthermore, 1c could suppress the progress of carrageenan-induced hind paw edema at a dosage of 50 mg/kg/day and dose-dependently ameliorate the development of adjuvant-induced arthritis (AIA). Docking study confirmed that 1c was an iNOS inhibitor with good binding into the active site of murine iNOS.

Influence of diabetes mellitus on long-term outcomes of patients with unprotected left main coronary artery disease treated with either drug-eluting stents or coronary artery bypass grafting.

Whether the effect of diabetes on patients with unprotected left main coronary artery (ULMCA) disease differs according to different strategies of revascularization was unknown. This study was conducted to evaluate the impact of diabetes on patients with ULMCA disease treated with either percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG).A total of 922 patients with ULMCA disease who received drug-eluting stent (DES) (n = 465) implantation or underwent CABG (n = 457) were retrospectively analyzed. We compared the effects of these 2 treatments on clinical outcomes (death, myocardial infarction, stroke, repeat revascularization, and the composite of death, myocardial infarction, or stroke), according to diabetic status.During the median follow-up of 7.1 years (interquartile range, 5.3 to 8.2 years), no difference was found between PCI and CABG in the adjusted occurrence of death (P = 0.112) and the composite endpoints of death, myocardial infarction, and stroke (P = 0.235). Significantly higher incidence of repeat revascularization (P < 0.001) was observed in the DES group, whereas the CABG group had a significantly higher rate of stroke (P = 0.001). These trends were consistent in both diabetic and nondiabetic patients. We did not observe significant interactions between treatment outcomes and the presence or absence of diabetes after adjustment for covariates (P(interaction) = 0.580 for the composite of death, MI and stroke, P(interaction) = 0.685 for death, P(interaction) = 0.416 for MI, P(interaction) = 0.470 for stroke, and P(interaction) = 0.502 for repeat revascularization).Presence of diabetes was not important for decision-making between CABG and PCI in patients with ULMCA disease.

[Clinical characteristics among CABG or PCI which to treat chronic kidney disease with unprotected left main coronary artery disease].

OBJECTIVE: To explore the clinical characteristics and prognosis of patients with chronic kidney disease with unprotected left main (ULM) coronary artery disease undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). METHODS: A total of 601 unprotected left main coronary artery disease patients were recruited. According to the values of endogenous creatinine clearance rate (Ccr), they were divided into three groups of <45 ml/min (n=40), 45-59 ml/min (n=96) and ≥60 ml/min (n=465). Retrospective comparisons were made for the clinical parameters and prognosis of ULM patients in different Ccr groups with different therapies. RESULTS: In Ccr≥60 ml/min group, the valves of left ventricular ejection fraction (LVEF) were lower in patients undergoing CABG. Patients with complete total occlusion (CTO) and complete revascularizations were much more than those undergoing PCI. In Ccr≥60 ml/min and Ccr 45-59 ml/min groups, multivessel disease was frequent in CABG-treated patients. No significant difference existed among three groups in major adverse cardiac and cerebrovascular event (MACCE), overall mortality or cardiac mortality. CONCLUSION: PCI is both safe and efficacious for chronic renal insufficiency patients with ULM.

[Long-term outcomes of patients with unprotected left main coronary artery disease post revascularization].

OBJECTIVE: To compare the long-term real-world outcomes of consecutive patients with unprotected left main coronary artery disease (ULMCA) underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and coronary artery bypass grafting (CABG). METHODS: Consecutive patients with ULMCA (defined as stenosis ≥ 50%) undergoing DES implantation or CABG between January 2003 to July 2009 in Beijing Anzhen Hospital were enrolled. The follow-up period extended through August 2013. The end points of the study were death, cardiac death, repeat revascularization, myocardial infarction (MI), stroke, the composite of cardiac death, MI or stroke and MACCE (major adverse cardiac and cerebrovascular events, the composite of cardiac death, MI, stroke or repeat revascularization). RESULTS: From January 2003 to July 2009, 922 ULMCA patients were enrolled in this study (465 PCI patients, and 457 CABG patients). The median follow-up was 7.1 years (interquartile range 5.3 to 8.2 years). The crude relative risk was as follows: overall death rate (13.0% (41/465) vs. 22.1% (72/457), P = 0.009), stroke rate (5.8% (11/465) vs. CABG 18.9% (46/457), P < 0.001) were significantly lower whereas the rate of repeat revascularization (32.3% (110/465) vs. CABG 19.2% (58/457), P < 0.001) was significantly higher in PCI group than in CABG group. MI rate was similar between PCI and CABG group (13.9% (33/465) vs. 6.7% (26/457), P = 0.196). MACCE rate was also similar between the 2 groups (42.9% (145/465) vs. 42.5% (142/457), P = 0.122). After multivariate adjusting, there was no significant difference in rates of death, MI and a composite of serious outcomes (cardiac death, MI, or stroke) between the 2 groups. Rates of MACCE were significantly higher in the PCI group (P = 0.009) due to increased rate of repeat revascularization (P < 0.001). However, stroke rate was still significantly higher in CABG group (P = 0.001) after multivariate adjusting. CONCLUSION: During a follow-up up to 8.2 years, the survival rate is similar between the PCI and the CABG group in patients with ULMCA disease. The rate of repeat revascularization is significantly higher and stroke rate is significantly lower in the PCI group compared to CABG group.

Synthesis and biological evaluation of 4-oxoquinoline-3-carboxamides derivatives as potent anti-fibrosis agents.

Thirty-one 4-oxoquinoline-3-carboxamides derivatives were synthesized and evaluated for their anti-fibrotic activities by the inhibition of TGF-ß1-induced total collagen accumulation and anti-inflammatory activities by the inhibition of LPS-stimulated TNF-α production. Among them, three compounds (10a, 10l and 11g) exhibited potent inhibitory effects on both TGF-ß1-induced total collagen accumulation and LPS-stimulated TNF-α production. Furthermore, oral administrations of 10l at a dose of 20 mg/kg/day for 4 weeks effectively alleviated lung inflammation and injury, and decreased lung collagen accumulation in bleomycin-induced pulmonary fibrosis model. Histopathological evaluation of lung tissue confirmed 10l as a potential, orally active agent for the treatment of pulmonary fibrosis.

The Misprediction of Helpers in Comforting Situations and Its Mechanism.

Background: As a prosocial behavior, comforting behavior can prompt individuals to provide emotional support to others. After the comforting behavior, the comforter may estimate the consoled individual's reaction, and this prediction will influence their future behavior. According to social cognition theory, competence dominates self-cognition, and warmth dominates the cognition of others, which impacts the prediction accuracy of comforters. They may overestimate the negative reaction of the consoled. This misprediction has also been confirmed for other prosocial behaviors, such as helping behavior and sharing behavior. Methods: In this study, 337 Chinese college students were investigated by convenience sampling. Through one real-world experiment and three imaginary-situation experiments, this study explored the phenomenon, effects and causes of the comforter's misprediction in the comfort condition. Results: SPSS 23.0 and statistical methods such as analysis of variance, an independent sample t-test and an intermediary test were used. The comforters overestimated the negative responses and underestimated the positive responses of the recipients, and the intensity of this misprediction increased in the comfort failure condition. The comforters' misprediction arose because the recipients were more concerned with the warmth dimension of the comforters, whereas the comforters were more inclined to focus on their own competence dimension. Conclusion: The comforter's prediction of the consoled's response was more negative than the actual situation, and this misprediction was more obvious when the consolation failed, which can be explained by social cognition theory. This study provides an understanding of how to relieve the psychological stress of comforters.

[Clinical characterization of patients with Danon disease].

OBJECTIVE: To analyze the clinical characterization of Danon disease caused by the mutation of lysosome-associated membrane protein-2 (LAMP-2) gene. METHODS: The clinical features, serum biochemical index, electrocardiogram and echocardiography data were retrospectively reviewed in 5 patients with genetically confirmed Danon disease. Mean follow-up period was (56 ± 6) months. RESULTS: Five patients including 2 men and 3 women in 2 unrelated families with 2 novel mutations in the exon 3 (c.189-190TGdel) and 8 (c.1205Cdel) of the LAMP-2 gene were identified. All patients had cardiomyopathy, 1 patient (1/5) had skeletal myopathy, and none of the patients had mental retardation. The two male patients presented cardiac symptoms at the age of 9 and 10 years, respectively, and all female patients were asymptomatic. Biochemical analysis showed that serum creatine kinase and liver transaminase enzyme were increased in 2 patients (2/5). Abnormal electrocardiogram was observed in all patients, and 2 patients (2/5) had ventricular preexcitation. During the follow-up. One male patient died of cardiac failure at the age of 18 years and three months, and the symptoms of the other male patients rapidly developed with the evolution from hypertrophic cardiomyopathy into dilated cardiomyopathy. However, all female patients remained asymptomatic, and repeat echocardiography indicated only mild ventricular hypertrophy during follow up. CONCLUSION: Patients with Danon disease mainly present hypertrophic cardiomyopathy, and sometimes presents with skeletal myopathy. The disorder occurs at early, age and progresses quickly and ends with poor prognosis in male patients. Other clinical features include elevations of serum creatine kinase and liver transaminase enzyme, ventricular preexcitation on electrocardiogram, and ventricular hypertrophy detected by echocardiography. Female patients remain asymptomatic till now in our cohort.

[Relationship between estimated glomerular filtration rate level and clinical characteristics and outcome in patients with angiographic coronary artery disease and normal serum creatinine].

OBJECTIVE: To explore the relationship between estimated glomerular filtration rate level and clinical characteristics and outcome in coronary artery disease (CAD) patients with normal serum creatinine. METHOD: A total of 548 hospitalized and angiographic CAD patients with normal fasting serum creatinine were enrolled. The kidney function was estimated by using the abbreviated modification of diet in renal disease (MDRD) study equation. Patients were divided into three groups according to eGFR tertiles: high eGFR group (eGFR > 88.15 ml×min(-1)×1.73 m(-2), n = 184); intermediate group ZU(70.30 ml× min(-1)×1.73 m(-2) < eGFR ≤ 88.15 ml×min(-1)×1.73 m(-2), n = 187); low eGFR group (eGFR ≤ 70.30 ml × min(-1)×1.73 m(-2), n = 177). Clinical data and cardiovascular risk factors were recorded after admission and during (14.02 ± 8.31) months follow up. The primary end point was combined major adverse cardiovascular and cerebral events (MACCE) including death, targeted vascular revascularization, non-fatal myocardial infarction, rehospitalization due to unstable angina and heart failure, and transient ischemic attack (TIA) and stroke. RESULTS: Patients in intermediate and low eGFR groups were older, more males, had more severe coronary artery disease, higher level of hsCRP, higher incidence of hypertension, and lower smoking rate than those in high eGFR group (all P < 0.05). A total of 89 MACCE were recorded during follow up. The level of eGFR was significantly lower in patients with MACCE than patients without MACCE [(73.76 ± 19.81) ml×min(-1)×1.73 m(-2) vs. (84.97 ± 23.42) ml×min(-1)×1.73 m(-2), P < 0.05]. Univariate and multivariate Cox regression analysis showed that eGFR was an independent predictor of MACCE in patients with CAD (univariate analysis: RR = 0.99, 95%CI:0.973-0.997, P < 0.05; multivariate analysis: RR = 0.98, 95%CI:0.976-0.998, P < 0.05). Kaplan-Meier survival analysis suggested that patients with low eGFR was linked with a decreased event free survival ratio (log-rank χ(2) = 7.271, P < 0.05). CONCLUSIONS: eGFR level in CAD patients with normal serum creatinine is associated with coronary artery severity, inflammation level and serves as an independent predictor for MACCE in this patient cohort.

Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly.

Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrillin-2 is related to the elasticity of the tissue and has been demonstrated to play an important role in the constitution of extracellular microfibrils in elastic fibers, providing strength and flexibility to the connective tissue that sustains the body's joints and organs. Methods: We recruited two Chinese families with arachnodactyly and bilateral arthrogryposis of the fingers. Whole-exome sequencing (WES) and co-segregation analysis were employed to identify their genetic etiologies. Three-dimensional protein models were used to analyze the pathogenic mechanism of the identified variants. Results: We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F). The structural models of the mutant FBN2 protein in rats exhibited that both the variants could break disulfide bonds. Conclusion: We detected two FBN2 variants in two families with CCA. Our description expands the genetic profile of CCA and emphasizes the pathogenicity of disulfide bond disruption in FBN2.

Identification of A Novel Variant of Filamin A Destroying the Attraction Between Benzene Rings and Sulfhydryl in Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH), characterized by acetabular deformity that manifests from loose ligaments to complete dislocation of the hip, can cause notable pain and dysfunction and lead to hip dislocation, secondary fractures, scoliosis, and osteoarthritis of hip. Variants in FLNA may produce a spectrum of malformations in multiple organs, especially the skeleton. This study aimed to identify the genetic etiologies of DDH patients and provide genetic testing information for further diagnosis and treatment of DDH. We recruited a Chinese woman with DDH and her family members. Whole-exome sequencing was used to identify the patient's genetic etiologies. Protein models were used to analyze the pathogenic mechanism of the identified variants. A novel variant (c.3493T>G, p.C1165G) of FLNA was detected. The structural models of the mutant FLNA protein indicated that the variant would lose its sulfhydryl side chain and destroy the attraction between benzene rings and sulfhydryl. We reported a novel variant (c.3493T>G, p.C1165G) of FLNA in a Chinese woman with DDH. Our research outcome enriches the gene pool for hip dysplasia and emphasizes the pathogenicity of sulfhydryl side chain disruption in FLNA.

[The value of SYNTAX score in predicting outcome patients undergoing percutaneous coronary intervention].

OBJECTIVE: To assess the value of SYNTAX score to predict major adverse cardiac and cerebrovascular events (MACCE) among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. METHODS: 190 patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention (PCI) with Cypher select drug-eluting stent were enrolled. SYNTAX score and clinical SYNTAX score were retrospectively calculated. Our clinical Endpoint focused on MACCE, a composite of death, nonfatal myocardial infarction (MI), stroke and repeat revascularization. The value of SYNTAX score and clinical SYNTAX score to predict MACCE were studied respectively. RESULTS: 29 patients were observed to suffer from MACCE, accounting 18.5% of the overall 190 patients. MACCE rates of low (≤ 20.5), intermediate (21.0 - 31.0), and high (≥ 31.5) tertiles according to SYNTAX score were 9.1%, 16.2% and 30.9% respectively. Both univariate and multivariate analysis showed that SYNTAX score was the independent predictor of MACCE. MACCE rates of low (≤ 19.5), intermediate (19.6 - 29.1), and high (≥ 29.2) tertiles according to clinical SYNTAX score were 14.9%, 9.8% and 30.6% respectively. Both univariate and multivariate analysis showed that clinical SYNTAX score was the independent predictor of MACCE. ROC analysis showed both SYNTAX score (AUC = 0.667, P = 0.004) and clinical SYNTAX score (AUC = 0.636, P = 0.020) had predictive value of MACCE. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score. CONCLUSIONS: Both SYNTAX score and clinical SYNTAX score could be independent risk predictors for MACCE among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score in this group of patients.

[Clinical characteristics of coronary artery disease patients with reduced left ventricular ejection fraction and their prognostic analysis].

OBJECTIVE: To explore the relationship between reduced left ventricular ejection fraction (LVEF) and characteristics of coronary artery disease (CAD) and investigate the association between reduced LVEF and cardiovascular prognosis. METHODS: A total of 677 hospitalized patients with angiographic CAD were enrolled. All patients' clinical data were recorded. LVEF were measured, high sensitive C-reactive protein (hs-CRP), white blood cell (WBC) and classic cardiovascular risk factors were recorded after admission. All patients were followed up from admission. The primary end point was combination occurrence of major adverse cardiovascular and cerebral events (MACCE), including death, targeted vascular revascularization, non-fatal myocardial infarction and rehospitalization due to unstable angina or heart failure, transient ischemic attack or stroke. RESULTS: All patients were tracked for (15±12) months, and patients were divided into normal LVEF group (LVEF≥0.50, n=585) and reduced LVEF group (LVEF<0.50, n=92) according to LVEF level. Compared with normal LVEF group, reduced LVEF group had more severe coronary stenosis (Gensini score: 62.85±41.45 vs. 47.68±33.26, P<0.05), a higher level of WBC and hs-CRP (WBC: 7.60±2.71 ×10(9)/L vs. 7.09±2.13 ×10(9)/L, hs-CRP: 5.68±3.97 mg/L vs. 3.97±3.75 mg/L, both P<0.05). A total of 146 MACCE occurred during follow-up periods. Compared with no-MACCE group, LVEF levels were significantly lower in MACCE group (0.576±0.113 vs. 0.603±0.101) and there were a higher level of hs-CRP and Gensini score in MACCE group (hs-CRP: 5.26±3.99 mg/L vs. 3.91±3.72 mg/L, Gensini score: 53.72±35.50 vs. 48.63±34.59, all P<0.05). Moreover, both of univariate and multivariate Cox regression analysis indicated LVEF be an independent predictor of MACCE in patients with CAD [univariate: relative risk (RR)=0.974, 95% confidence interval (95%CI) 0.960 to 0.988, P=0.000; multivariate: RR=0.979, 95%CI 0.961 to 0.998, P=0.033]. Kaplan-Meier analysis suggested that patients with reduced LVEF had an increased MACCE occurrence (χ(2)=14.56, P<0.05). CONCLUSION: LVEF level may be associated with coronary artery severity, and could be independently predict the prognosis of CAD.

Improving the ischemia-reperfusion injury in vascularized composite allotransplantation: Clinical experience and experimental implications.

Long-time ischemia worsening transplant outcomes in vascularized composite allotransplantation (VCA) is often neglected. Ischemia-reperfusion injury (IRI) is an inevitable event that follows reperfusion after a period of cold static storage. The pathophysiological mechanism activates local inflammation, which is a barrier to allograft long-term immune tolerance. The previous publications have not clearly described the relationship between the tissue damage and ischemia time, nor the rejection grade. In this review, we found that the rejection episodes and rejection grade are usually related to the ischemia time, both in clinical and experimental aspects. Moreover, we summarized the potential therapeutic measures to mitigate the ischemia-reperfusion injury. Compare to static preservation, machine perfusion is a promising method that can keep VCA tissue viability and extend preservation time, which is especially beneficial for the expansion of the donor pool and better MHC-matching.