Objective:To assess the combination of conventional ultrasound with contrast-enhanced ultrasound(CEUS)in the diagnosis of urothelial carcinoma(UC)of the renal pelvis in elderly patients.Methods:Sixty-seven elderly patients with a histopathologic diagnosis of UC of the renal pelvis and surgically treated at our hospital between April 2015 and March 2023 were retrospectively analyzed.Characteristics of regular preoperative 2D ultrasound, color Doppler flow imaging(CDFI)and CEUS were examined.Results:Of 67 patients, 49(73.13%)were found to have localized lesions in the renal pelvis and renal calyces.Lesions in 53 patients(79.10%)could be clearly identified by conventional ultrasound, with 46(86.79%)being isoechoic or hypoechoic, and 7(13.21%)being hyperechoic.Analysis of tumor blood flow by CDFI found 22 cases(41.51%)with avascular lesions, 21(39.62%)with hypovascular lesions and 10(18.87%)with hypervascular lesions.The average value of the resistance index(RI)was 0.64.Enhancement was seen in 62 lesions(92.54%)by CEUS after injection of SonoVue.Compared with the cortex of the ipsilateral kidney, a slow enhancement pattern was observed in 46(74.19%), 14(22.58%)showed simultaneous enhancement, and 2(3.23%)showed fast enhancement.At peak enhancement, 43 lesions(69.35%)had hypo-enhancement, 10(16.13%)had iso-enhancement, and 9(14.52%)had hyper-enhancement, compared with the cortex.Concerning the homogeneity of enhancement, 16(25.81%)displayed heterogeneous enhancement, with tumor necrosis or hemorrhage, and 46(74.19%)had homogeneous enhancement.When the contrast agent washout rate was assessed, a fast washout pattern was observed in 53(85.48%), synchronous washout in 6(9.68%), and slow washout in 3(4.84%).Conclusions:UC of the renal pelvis mostly shows isoechoic and hypoechoic lesions on conventional ultrasound, avascular or hypo-vascular lesions on CDFI, and slow-in, fast-out and hypo-enhancement on CEUS, compared with the cortex.Conventional ultrasound combined with CEUS can help improve the diagnostic accuracy of UC of the renal pelvis.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

Objective:To investigate the genetic etiology of fetal conotruncal heart defects (CTDs) and to evaluate the performance of copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in identifying the genetic etiology.Methods:This retrospective study involved 196 fetuses diagnosed with CTDs by fetal echocardiography in Beijing Anzhen Hospital, Capital Medical University from June 2017 to December 2021. CNV-seq was performed to screen for chromosomal abnormalities [aneuploidy and copy number variations (CNVs)] in the fetuses and their parents, and then WES was performed if CNV-seq was negative. The diagnostic yields of genetic abnormalities [aneuploidy+CNVs+single nucleotide variations (SNVs)] for different types of CTDs were compared using Chi-square test. Results:CNV-seq revealed 54 cases (27.6%, 54/196) with chromosomal abnormalities, including 14 (7.1%, 14/196) aneuploidies, 39 (19.9%, 39/196) CNVs and one aneuploidy complicated by CNVs. Together with another 13 fetuses with pathogenic or likely pathogenic SNVs detected by WES among the rest 142 cases whose CNV-seq results were negative, the total detection rate of genetic abnormalities was 34.2% (67/196). WES increased the diagnostic yield for CTDs by 9.2% (13/142). There was significant difference in the diagnostic yields for different types of CTDs ( χ2=20.31, P=0.002). The diagnostic yield was relatively high for interrupted aortic arch of type B, absent of the pulmonary valve -type of tetralogy of Fallot (9/10 and 8/12), but low for transposition of the great arteries (12.5%, 5/40). Conclusions:CNVs are the common genetic abnormalities in fetal CTDs, and SNVs are also detected in some cases. It is recommended that all fetuses with CTDs should undergo genetic testing. CNV-seq should be used in combination with WES if possible to improve the identification of genetic etiology and provide reference for genetic counseling.

Objective:To construct and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) of patients with late-stage hepatocellular carcinoma (HCC).Methods:A retrospective cohort study was used in this report. Screened 2382 late-stage HCC patients obtained from Surveillance, Epidemiology, and End Results (SEER) database (2010—2015), were randomly classified into the training cohort and the internal validation cohort by using the function in R software according to the ratio of 1∶1. Chi-square test was applied to verify the comparability of data between two groups. The external validation cohort ( n=62) were collected from the Affiliated Zhangjiagang Hospital of Soochow University. Based on univariate and multivariate COX regression analyses in the training cohort, this study constructed nomograms for 6- and 12- month OS and CSS. Concordance index (C-index), calibration plots, the receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were applied to measure the performance of nomograms in the training cohort and to validate nomograms in two validation cohorts. The clinical utility was measured by decision curve analysis (DCA). Results:Two nomograms were constructed. The identified risk factors included sex, Edmondson-Steiner grade, T stage, N stage, M stage, tumor size, bone metastasis, Alpha-fetoprotein (AFP), surgery of primary site, radiation and chemotherapy. The C-index for OS in the training and two validation cohorts was 0.729(95% CI: 0.711-0.747), 0.721(95% CI: 0.705-0.737) and 0.860(95 CI: 0.831-0.889), respectively. The C-index for CSS in the training and two validation cohorts was 0.732(95% CI: 0.714-0.750), 0.725(95% CI: 0.707-0.743) and 0.862(95% CI: 0.829-0.895), respectively. Afterwards, for nomograms in the training and two validation cohorts, C-index and calibration plots expressed great predictive accuracy and concordance. ROC curves and Kaplan-Meier survival curves demonstrated good prognostic ability. Furthermore, nomograms performed superior to other models. DCA showed substantial clinical utility. Conclusion:This study has developed and validated nomograms predicting 6- and 12- month OS and CSS of patients with late-stage HCC, which may be useful to develop the individualized treatment.

Objective:To summarize the etiological mechanism, echocardiographic and clinical features of fetal cardiomyopathies (FCMs).Methods:According to the data of echocardiography in Maternal-Fetal Medicine Center in Fetal Heart Disease of Beijing Anzhen Hospital during 2015 January to 2020 December, 70 cases with FCMs were retrospectively reviewed, and the clinical, ultrasonic, pathological and clinical outcome data were collected. Whole exome sequencing and whole genome sequencing were used to identify the genetic changes.Results:Primary FCMs were diagnosed in 55 cases (78.6%, 55/70), including 39 fetuses with non-compaction of the ventricular myocardium (NVM), 10 with dilated cardiomyopathy (DCM), 5 with hypertrophic cardiomyopathy (HCM), and 1 with restricted cardiomyopathy (RCM). Secondary FCMs were diagnosed in 15 cases (21.4%, 15/70), including 7 fetuses with maternal anti-Ro/La antibodies (presenting with DCM), 4 with twin-twin transfusion syndrome (2 with DCM and 2 with HCM), 2 with fetal anemia (presenting with DCM), 1 with maternal diabetes (presenting with HCM) and 1 with chorioangioma of the placenta (presenting with DCM). In all cases, 9 cases were born, 3 cases died in perinatal period, and 58 pregnancies were terminated due to ineffective treatment or the decisions of pregnant women. Thirty cases with primary FCMs were performed with genetic tests, and 13 of them were identified with positive genetic changes related to FCMs, including 12 cases with NVM and 1 with HCM.Conclusions:Primary FCMs are more common than secondary FCMs in fetal period. The genetic disorders have a high proportion in fetal NVM. Fetal DCM and HCM have a large spectrum of intrinsic and extrinsic causes.

Objective:To evaluate the heart hemodynamics in fetuses with premature ductus arteriosus constriction or closure using fetal heart quantification (FHQ).Methods:The clinical data of 50 singleton fetuses with ductus arteriosus constriction ( n=35) or ductus arteriosus closure ( n=15) who underwent echocardiography in Department of Ultrasound, Beijing Anzhen Hospital were retrospectively analyzed, from May 2013 to January 2020. Fifty healthy singleton fetuses were randomly selected as the control group. The ductus arteriosus diameter (DA), pulsatility index (PI), diameter of the left atrium(LA) and right atrium(RA), diameter of the left ventricle (LV) and right ventricle (RV), tricuspid regurgitation/right atrium area ratio (TR/RA Ratio), pressure gradient of tricuspid regurgitation (PG of TR), and heart/chest ratio were measured using conventional fetal echocardiography; the correlations among the parameters were analyzed. Speckle-tracking analysis was used to analysis and compute the LV and RV global spherical index (GSI), fractional area change (FAC) and global strain (GS), the LV ejection fraction(EF) and stroke volume (SV). These variables and their correlations were compared and analyzed. Results:Compared with the control group, the GS and FAC of the LV and RV in the ductus arteriosus constriction or closure groups were lower ( P<0.05) while the LV-SV was higher ( P<0.05). The FAC, GS, and EF values of the LV were higher in the premature ductus arteriosus closure group than in the ductus arteriosus constriction group ( P<0.05), while the RV-FAC was lower ( P<0.05), the RV-GS and LV-SV showed no significant changes ( P>0.05). Correlation analyse showed that the PI was positively correlated with DA( r=0.364, P<0.05); the PG of TR was negatively correlated with DA( r=-0.414, P<0.05); the TR/RA Ratio was negatively linearly correlated with PI( r=-0.388, P<0.05), and positively correlated with RV/LV Ratio ( r=0.369, P<0.05); the other parameters were not significantly correlated with the DA or PI ( P>0.05). Conclusions:Fetal heart hemodynamics in the premature ductus arteriosus constriction or closure groups change significantly, FHQ can provide valuable information for the evaluation of the fetal heart with ductus arteriosus constriction or closure.

Objective:To investigate the fetal echocardiographic features and clinical phenotype of 22q11.2 microdeletion syndrome (22q11.2DS) and provide information for the diagnosis of fetal 22q11.2DS.Methods:We retrospectively retrieved information of 822 fetuses, who were diagnosed with congenital heart disease by fetal echocardiography, with results of low-coverage whole genome sequencing from the Genetic Database of Beijing Key Laboratory of Fetal Heart Disease and Maternal Fetal Medicine Research from January 2013 to April 2019. Phenotype, fetal echocardiographic features and genetic origin results of 46 fetuses with 22q11.2DS (22q11.2DS group) were summarized. Another 68 fetuses who were negative for 22q11.2DS but had conotruncal defects(CTD) were selected as control. Differences in fetal cardiac axis were compared between the two groups. Independent samples t test and Chi-square test were used for statistical analysis. Results:22q11.2DS was detected in 46 fetuses giving a total detection rate of 5.60% (46/822). The detection rates of 22q11.2DS in fetuses with CTD and non-CTD were 14.8% (45/305) and 0.2% (1/517), respectively ( χ2=74.253, P<0.001). Fetal cardiac axis was left-deviated in those with 22q11.2DS compared with those of the control [(61.7±15.3)°vs (55.7±13.4)°, t=-3.843, P=0.001]. Conclusions:CTD are the common clinical phenotypes of fetal 22q11.2DS. Fetal 22q11.2DS should be considered and the corresponding prenatal genetic diagnosis is highly suggested when the fetus is diagnosed with CTD especially combined with an enlarged cardiac angle.

Objective:To summarize the echocardiography and pathological features of fetal Kabuki syndrome.Methods:This study retrospectively analyzed the echocardiography and pathological features of seven fetuses with KMT2D pathogenic variants confirmed by copy number variation sequencing, and who were identified as complex congenital heart disease by fetal echocardiography, at Beijing Anzhen Hospital, Capital Medical University and other multi-center collaborative hospitals on fetal congenital heart diseases from January 2013 to May 2018. All the seven fetuses were artificially aborted. Descriptive statistics were used for data analysis. Results:(1) The seven pregnant women aged 29 (27-32) years and had an abortion at 23 (22-25) gestational weeks. There were three male and four female fetuses. (2) Pathogenic mutations in KMT2D gene were detected in all seven cases, including one nonsense mutation and six frameshift mutations. (3) All fetuses had left heart obstruction with or without aortic arch dysplasia/interruption of the aortic arch. There were three with hypoplastic left heart syndrome, two with a single ventricle, one with aortic atresia, and one with severe mitral valve dysplasia. Other cardiovascular abnormalities included aortic arch branch abnormalities, double-outlet of the right ventricle, ventricular septal defect, tricuspid atresia, pulmonary valve stenosis (nearly atresia) complicated by pulmonary dysplasia, persistent left superior vena cava, and patent or closed foramen ovale. Secondary changes included enlargement of the right atrium and right ventricle, and dilatation of the pulmonary artery or ductus arteriosus. (4) Four of the seven fetuses showed multiple extracardiac system abnormalities, including facial deformities (two cases), pulmonary dysplasia (two cases), digestive abnormalities(two cases), and urogenital system abnormalities (two cases). Conclusions:The main features of echocardiography for fetal Kabuki syndrome are left heart obstruction, often complicated by other congenital cardiovascular abnormalities.

Objective To investigate the predictive role of the intraoperative amylase ( IOA ) from pancreatic stump for postoperative pancreatic fistula. Methods The clinical data of 26 patients who received distal pancreatectomy ( DP) and central pancreatectomy ( CP) in the Shanghai Ruijin Hospital from June 2017 to July 2018 were retrospectively analyzed. IOA and peri-operative potential clinical factors associated with pancreatic fistula were analyzed. Receiver operating characteristics ( ROC) curve was drawn to evaluate the diagnostic efficacy of IOA from pancreatic stump in predicting postoperative pancreatic fistula, and the sensitivity and specificity were calculated. Results Of 26 patients, 19 patients underwent DP and 7 patients underwent CP. 9 patients (34.6％,9/26)had class A pancreatic fistula (biochemical leak) and 11 patients (42. 3％,11/26) had class B pancreatic fistula after surgery, and no class C pancreatic fistula occurred. Univariate analysis showed that IOA from pancreatic stump in clinically relevant pancreatic fistula group was higher than that in clinically irrelevant pancreatic fistula group(7971. 82 ± 4387. 98 vs 1589. 20 ± 1405. 00, P=0. 001). Area under the curve ( AUC) of IOA in predicting the development of clinically relevant pancreatic fistula after surgery was 0. 921 and 95％ confidential interval was 0. 807-1. 000. The optimal cut-off value was 3622 U/L , and the sensitivity and specificity were 90. 9％ and 86. 7％. Conclusions IOA from pancreatic stump could serve as a clinical indicator for predicting the occurrence of postoperative pancreatic fistula.