Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .

PURPOSE: To explore the molecular mechanism of the upregulation of multidrug resistance-associated protein 4 (MRP4) in cholestasis. MATERIALS AND METHODS: The mRNA and protein levels of MRP4 in liver samples from cholestatic patients were determined by quantitative real-time PCR and Western blot. In human hepatoma HepG2 cells, electrophoretic mobility shift assay (EMSA) was used to determine the affinity of nuclear factor-E2-related factor (Nrf2) binding to MRP4 promoter. Dual-luciferase reporter assay was used to detect the binding of tumor necrosis factor α (TNFα) to the promotor of E2F1. The bile duct ligation mouse models were established using male C57BL/6 mice. RESULTS: The mRNA and protein levels of MRP4 were significantly increased in cholestatic patients. TNFα treatment induced the expression of MRP4 and Nrf2 and enhanced cell nuclear extract binding activity to MRP4 promoter, as demonstrated by EMSA. Nrf2 knockdown reduced MRP4 mRNA levels in both HepG2 and Hep-3B cells. In addition, TNFα increased Rb phosphorylation and expression of MRP4 and Nrf2 and activated E2F1 and phosphorylated p38 in HepG2 and Hep-3B cells. These effects were markedly inhibited by pretreatment with E2F1 siRNA. Dual-luciferase reporter assay validated that TNFα induces the transcription of E2F1. Furthermore, the expression of MRP4, Nrf2, E2F1, and p-p38 proteins was improved with treatment of TNFα in a mouse model of cholestasis. E2F1 siRNA lentivirus or SB 203580 (p38 inhibitor) inhibited these positive effects. CONCLUSION: Our findings indicated that TNFα induces hepatic MRP4 expression through activation of the p38-E2F1-Nrf2 signaling pathway in human obstructive cholestasis.
Animals ; Bile Ducts ; Blotting, Western ; Carcinoma, Hepatocellular ; Cholestasis ; Electrophoretic Mobility Shift Assay ; Hep G2 Cells ; Humans ; Lentivirus ; Ligation ; Liver ; Male ; Mice ; Multidrug Resistance-Associated Proteins ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; RNA, Small Interfering ; Tumor Necrosis Factor-alpha ; Up-Regulation

OBJECTIVE: To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations. METHODS: Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production. RESULTS: Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous. CONCLUSION The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
Adrenal Insufficiency ; DAX-1 Orphan Nuclear Receptor ; genetics ; Humans ; Hypoadrenocorticism, Familial ; genetics ; Male ; Mutation ; Mutation, Missense ; Pedigree ; Repressor Proteins

Objective: To investigate the safety and clinical efficacy of comprehensive endovascular treatment for acute deep vein thrombosis(DVT)in elderly patients. Methods: Clinical data of 94 elderly patients who underwent endovascular treatment from June 2013 to June 2016 were retrospectively analyzed.All patients underwent inferior vena cava filter implantation(IVCF). Of them, 57 patients initially underwent thrombectomy and subsequently received the adjunctive catheter-directed thrombolysis(CDT)(Group A)and 37 cases underwent CDT(Group B). Clinical efficacy and safety of treatments in the two groups were examined. Results: Among the 94 patients, 88 cases had retrievable IVCF, and the retrieval rate was 94.3%(83/88). There were significant differences in total infusion time(73.92±31.68 h vs.156.2±30.2 h)and total doses of infused thrombolytic agents(180.71±44.83 million unit vs.355.0±96.0 million unit)between Groups A and B(P<0.05). There was a significant difference in average hospitalized time between Groups A and B(9.4±2.4 d vs.12.8±4.3 d, t=-4.99, P<0.01). There was no significant difference in clinical efficacy between Groups A and B(χ²=1.263, P>0.05). Fifty-six patients were treated with angioplasty(PTA), 34 of them were combined with stent implantation, and there was no difference between the two groups(χ²=1.128, P>0.05). Neither of the two groups saw serious complications.The incidence of minor hemorrhage was 9.6%(9/94), including 2 cases and 7 cases in Group A and Group B respectively, and the difference was statistically significant(χ²=4.503, P=0.034). The average follow-up time was 16.7±8.3 months in the 94 patients, and the stent patency rate was 91.2%(31/34). Doppler ultrasonography results at the last follow-up showed that the reverse flow rate of the valve was 20.2%(19/94), the occurrence rates of post-thrombotic syndrome(PTS)were 24.6%(14/57)and 29.7%(11/37)in Group A and Group B respectively, and the difference was not statistically significant(χ²=0.307, P=0.580). Patients in the mild, moderate and severe stages assessed by Villata scoring were 9 vs.6, 4 vs.5, 0 vs.1 in Group A and Group B respectively, and the differences were not statistically significant(χ²=0.007 and 0.205, P>0.05). Conclusions It is safe and effective for elderly patients with DVT when timely and appropriate the treatment strategies are chosen and comprehensive approaches including IVCF, anticoagulation, endovascular CDT, thrombectomy, PTA and stent implantation are used.

Objective To investigate the clinical value of vitamin D receptor ( VDR) gene polymorphism in lung cancer screening .Methods From January 2017 to September 2017 ,2000 lung cancer screening patients in the Fifth People's Hospital of Foshan were selected in the research .The VDR gene polymorphism was determined by phenol-chloroform method .DNA was extracted from the peripheral blood of patients ,different VDR genotypes [ Bsm1 bb and Bb),Apal(aa,Aa and AA)] were analyzed by univariate analysis to determine the correlation between lung cancer and VDR gene polymorphism and lung cancer incidence by multivariate non -conditional logistic regression analysis, thus to explore the relationship between different VDR genotypes and risk factors of lung cancer . Results The level of serum vitamin D in the non -lung cancer patients was (46.5 ±2.3) ng/L,which was signifi-cantly higher than (26.5 ±1.1)ng/L in the lung cancer patients (t=49.614,P=0.000).The Bsm1bp genotype, Apal aa genotype and Apal Aa genotype were the risk factors of lung cancer .The Bsm1bp and Apal Aa genotypes were independent risk factors of lung cancer .Conclusion The Bsm1 locus and Apal locus Aa genotype in VDR receptor are high risk population of lung cancer .Therefore,we should pay more attention to the clinical screening and avoid misdiagnosis and missed diagnosis .

Objective To assess the safety and efficacy of catheter-directed thrombolysis combined with percutaneous transluminal angioplasty (PTA) in treating acute thrombo-embolism of artificial arteriovenous fistula.Methods The clinical data of 64 patients with acute thrombo-embolism of artificial arteriovenous fistula (84 events in total),who were admitted to single medical center during the period from January 2012 to September 2016,were retrospectively analyzed.The diagnosis of acute thrombo-embolism of artificial arteriovenous fistula was confirmed by angiography via femoral approach in all patients.Mechanical thrombectomy of the thrombotic occlusion segment by using common guide wire was carried out first,which was followed by bolus injection of urokinase (125,000-375,000 units);if the thrombus was not completely dissolved the catheter would be retained and the urokinase would be continuously infused with a micro-pump until the thrombus was completely dissolved.Conventional balloon dilatation would be employed when the stenosis of artificial arteriovenous fistula lumen was ＞50％ or the stenosis impeded the performance of dialysis.Kaplan-Meier survival curve was used to estimate the primary and secondary cumulative patency rates after the first intervention.Results Of the 84 interventional procedures,technical success was achieved in 69 procedures (82.1％).A total of 14 conventional balloon dilatation procedures had to be conducted as the fistula was seriously narrowed,and up to 12 procedures (85.7％) were succeeded.The overall clinical success rate was 78.5％ (66/84).During the therapeutic course,bleeding event occurred in 7 procedures (8.3％),including major bleeding (n=3) and minor bleeding (n=4).After the treatment,the 3-,6-,12-,24-month primary and secondary patency rates were 76.1％,63.6％,40.8％,12.5％ and 81.3％,70.8％,47.0％,32.5％respectively.Conclusion For the treatment of acute thrombo-embolism of artificial arteriovenous fistula,catheter-directed thrombolysis is safe and effective,it can assist conventional balloon dilatation therapy to obtain satisfactory therapeutic result for internal fistula stenosis.

Objective To compare the safety and clinical efficacy of recombinant human tissue plasminogen activator (rt-PA) and urokinase(UK)in catheter-directed thrombolysis(CDT)for the treatment of subacute iliofemoral deep venous thrombosis(DVT). Methods From June 2013 to June 2017, a total of 116 subacute DVT patients underwent consistent CDT with either rt-PA or urokinase, or simple anticoagulation treatment in this study.The patients were divided into three groups for comparison:rt-PA-CDT group(n=43), UK-CDT group(n=39)and anticoagulation group(n=34). The baseline data, thrombolysis duration, rt-PA or UK dosages, thrombolytic rate and clinical efficacy rate were compared among the three groups. Independent t-test(accorded to normal distribution)was used to analyze the thrombolysis duration.The quantitative data were analyzed with analysis of varianc and the qualitative data were compared by the chi-square test. Results There was no significant difference in general clinical features among the three groups(P>0.05). The thrombolysis duration, total dosages and thrombolytic rate (≥50)were(5.8±1.3)d,(49.7±16.1)mg,86.0% for rt-PA-CDT group,and(6.3±1.5)d,(440±99)×104 U, 66.7% for UK-CDT group.The difference of thrombolysis duration was not statistically significant between the rt-PA-CDT group and UK-CDT group(t=-1.868, P>0.05). The thrombolysis rate of rt-PA-CDT group was significantly higher than that of UK-CDT group(χ2=4.315, P<0.05). The time of obtaining grade Ⅲthrombosis rate was shorter for rt-PA-CDT group(4.7±0.9)d compared with UK-CDT group(6.0±1.2 d) (t=-2.343,P<0.05).The clinical efficacy rates of the rt-PA-CDT group[88.4%(38/43)]and UK-CDT group [76.9%(30/39)]were significantly higher than that of anticoagulation group[26.5%(9/34)](P<0.05).There was no statistical difference between the rt-PA-CDT group and UK-CDT group(χ2=1.893, P>0.05). No severe complications were found in all groups. The incidence rates of mild complication of the rt-PA-CDT group, UK-CDT group and anticoagulation group were 16.3%(7/43), 17.9%(7/39)and 8.8%(3/34), respectively, and there were no significant differences among the three groups(χ2=1.396, P>0.05). Conclusion The clinical efficacy of CDT using rt-PA and UK for subacute DVT is better than simple anticoagulation treatment.Thrombolytic rate of rt-PA is superior to UK.

Objective To evaluate the clinical value of percutaneous AngioJet thrombectomy for acute iliofemoral deep venous thrombosis.Methods 50 patients were divided into AngioJet thrombectomy group(25 cases) compared with bolus injection of urokinase through catheter in control group (25 cases).When the thrombosis was completely dissolved,the PTA and stents were implanted in those patients presenting May-Thurner syndrome in both groups.Inferior vena cava filter was retrieved from the patients and the thrombolytic therapy was discontinued.The patency rate of iliofemoral venous was assessed by CTA at 1 and 6 months after the procedure.Results The average dosage of urokinase in AngioJet patients was (880 000 ± 354 000) units.The mean duration time of catheter-directed thrombolysis was (42.2 ± 16.7) hours and the average hospitalization time is (3.8 ± 0.8) days.Grade Ⅲ thrombolysis was achieved in 18 limbs and grade Ⅱ lysis in 6 limbs,grade Ⅰ lysis in 1 limb.The mean duration time of catheter-directed thrombolysis was (129.6 ± 32.2) hours.The average dose of urokinase was (4 100 000 ± 1 060 000) units and the average hospitalization time was (7.9 ± 1.4) days in control group.Grade Ⅲ thrombolysis was achieved in 10 limbs,grade Ⅱ lysis in 9 limbs and grade Ⅰ lysis in 6 limbs.The dosage of urokinase,duration time of catheter-directed thrombolysis,time in hospital and clinical effects were statistically different between the two groups (all P ＜ 0.05).There were no recurrent thrombosis in all the patients after 6 months of treatment.Venous patency was maintained in all patients with implanted stent.Conclusions Percutaneous AngioJet thrombectomy with adjunctive thrombolytic therapy is an effective,safe treatment modality in patients with acute iliofemoral vein thrombosis.

Objective To compare the clinical efficacy of angioJet rheolytic thrombectomy (ART) and manual aspiration thrombectomy (MAT) combined with catheter-directed thrombolysis (CDT) in the treatment of acute iliofemoral venous thrombosis (IFVT).Methods 62 acute IFVT patients undergoing interventional treatment with either ART (group A,30 cases) or MAT (group B,32 cases) from 2014 to 2016,were enrolled in this study.Clinical efficacy and postthrombotic syndrome (PTS) rate were compared between the two groups.Results The instant thrombolysis rate in group A was 83.3％ (25/30),that was 59.4％ (19/32) in group B(P ＜ 0.05).Time used for adjunctive thrombolysis and dosages of UK in group A were (73.92 ±31.68)h and (110.71 ±44.83) × 104 U,while in Group B were (121.20 ±25.20)h and (313.49 ± 70.11) × 104 U,respectively (P ＜0.01).Final thrombolysis rate of these two groups were 93.3％ (28/30) and 87.5％ (28/32) (P ＞ 0.05).No severe complications occurred during the treatment of ART and MAT procedure.Fifty seven cases (91.9％) were followed-up,the valvular regurgitation rate in group A and group B were 14.3％ (4/28) and 37.9％ (11/29),respectively (P ＜ 0.05).PTS rate in group A was 25.0％ (7/28) and 37.9％ (11/29) in group B (P ＞0.05).Conclusions Interventional treatment for acute IFVT with ART and MAT can both achieve high clinical efficacy.ART are with higher instant thrombolysis rate and less valvular regurgitation compared with MAT.

Objective To evaluate the characteristics of spatial distribution and time accumulation of impact acceleration at different parts of human body during backward falling process. Methods Four healthy men and four healthy women (20-20 years old) were enrolled. The tri-axial acceleration on head, chest, left/right arm/hand/foot, left/right front/back hip, left/right femur head, sacrum and coccyx throughout the backward falling were measured by ADXL335 tri-axial acceleration sensor. Systemic acceleration distribution of backward falling was polynomial fitted by signal magnitude vector (SMV) of its first peak. Besides, parameters of impulse mechanics such as zero-g time, total falling time, peak SMV, relative pressure impulse of the vulnerable sites (head, hip and its related sites) were also calculated. Results Compared with the other parts of the body, the peak SMV and relative impulses of left/right back hip and head were significantly higher (P＜0.05). Acceleration that paralleled to the ground in left/right back hip was also relatively large. The rotational transform angles of left/right back hip, left/right femur head, sacrum and coccyx were significantly larger (P＜0.05). In addition, during the process of falling backward to the ground, a sliding tendency toward the sagittal plane 53.58°±6.75° occurred at all testing sites. Conclusions Head and hips are vulnerable during backward falling, and their zero-g time (0.26±0.05) s can be used as the longest starting time of falling protection devices. The large change angle of left/right hip, left/right femoral head, sacrum and coccyx may be the important cause of the sprain during backward falling.