Objective:To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3 (BASD3) disorder caused by CYP7B1 gene variation.Methods:This was a case series study. Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases, Children′s Hospital of Fudan University at Xiamen and Department of Pediatrics, Women and Children′s Hospital, School of Medicine, Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed. Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of " Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3" and "CYP7B1 liver" both in Chinese and English. The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized.Results:Two BASD3 patients, 1 male and 1 female, were admitted at the ages of 3 months and 18 days, and 2 months and 7 days, respectively. Both patients presented with neonatal cholestasis and hepatomegaly. Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels, while gamma-glutamyltransferase (GGT) and total bile acid levels were normal or nearly normal. Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15) and c.334C>T(p.Arg112Ter). Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid (CDCA). Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter) in CYP7B1 gene. Patient 2 was in liver failure status already and not reactive to oral CDCA administration. Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin. Literature review revealed no cases of BASD3 reported in Chinese literature, including 2 patients in this study, while 12 patients (9 males and 3 females) were reported in 9 English literatures. All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis, liver failure, kidney enlargement, hypoglycemia, and spontaneous bleeding in some cases, polycystic kidney disease was demonstrated in 5 cases of them. The c.334C>T (p.Arg112Ter) of the CYP7B1 gene was homozygous in 4 cases and compound heterozygous in 2 cases. Among the 12 children, 6 cases received CDCA treatment, while 6 cases not. Four survived with their native liver in the 6 cases who received CDCA therapy, while none in the 6 cases not received CDCA therapy.Conclusions:BASD3 is a rare hereditary cholestatic disorder. Markedly elevated levels of conjugated bilirubin and aminotransferases, with normal or nearly normal GGT and total bile acid levels can serve as diagnostic clue. c.334C>T is the most common pathogenic variant of the CYP7B1 gene. Timely administration of CDCA may save the liver.

Objective:To investigate the value of Breast Ultrasound Report and Data System (BI-RADS) classification in diagnosis of special types of breast cancer.Methods:A total of 112 patients with special type of breast cancer (112 breast lesions) confirmed by pathology were analyzed by using BI-RADS ultrasound category in the Second Affiliated Hospital, Zhejiang University School of Medicine from August 2009 to August 2020. All patients underwent ultrasound before surgery. The breast lesions were evaluated by senior attending and junior resident according to BI-RADS ultrasound category respectively. Taking histopathological result as the gold standard, the sensitivity and accuracy of BI-RADS classification in the diagnosis of special types of breast cancer were calculated.The differences between different special types of breast cancer in terms of ultrasound characteristics and pathological features were analyzed. Kappa consistency test was used to evaluated the consistency of the results of two physicians.Results:In the 112 patients, pathological results showed that there were 20 cases of metaplastic carcinoma, 19 cases of invasive carcinoma with medullary features, 16 cases of differentiated carcinoma of apocrine gland, 12 cases of mucinous carcinoma, 12 cases of invasive micropapillary carcinoma, 10 cases of invasive papillary carcinoma, 6 cases of invasive lobular carcinoma and 17 cases of other special types of carcinoma. Among them, 4 cases (3.5%) were BI-RADS 3, 13 cases (11.6%) were BI-RADS 4a, 42 cases (37.5%) were BI-RADS 4b, 47 cases (42.0%) were BI-RADS 4c and 6 cases (5.4%) were BI-RADS 5. The accuracy and sensitivity of BI-RADS classification in diagnosis of special types of breast cancer was 96.43% and 96.43%, respectively. There was significant difference in BI-RADS grade among different special types of breast cancer ( P<0.05). Most lesions were characterized by hypoechoic with irregular shape and angular or microlobulated margin. The nodule size, boundary, echo and posterior echo in breast cancer with different special types showed significant differences (all P<0.05). There was a good consistency between the two physicians (Kappa=0.789). Conclusions:The ultrasonography features of different special types of breast cancer are different. BI-RADS classification has great value in diagnosis of special types of breast cancer.

Objective To explore the safety and clinical value of percutaneous ultrasound‐guided core needle biopsy( PUS‐CNB) and endoscopic ultrasound‐guided fine needle aspiration( EUS‐FNA ) in pancreas mass . Methods Ultrasound‐guided biopsy were performed in 109 cases who were difficult to diagnose to get specimens from the highly suspicious parts of the lesions by avoiding vessels . PUS‐CNB were performed in 82 cases , EUS‐FNA in 19 cases and both in 8 cases . T he site and size of lesions were recorded preopeartion . Specimens with clear pathological diagnosis were considered as satisfactory materials . Specimens that were impossible to puncture due to the existence of high risk factors in the process of puncture were considered as unsuccessful biopsy . All patients were followed up after biopsy and complications were recorded . Results The satisfaction rate and success rate of PUS‐CNB were 98 .89% and 100% ,the diagnostic accuracy and false negative rate were 97 .78% and 2 .22% . T he satisfaction rate and success rate of EUS‐FNA were 96 .15% and 96 .30% ,the diagnostic accuracy and false negative rate were 80 .77% and 23 .81% . T here were no serious complications such as pancreatic fistula ,hemorrhage and needle transfer at the needle site after puncture . Conclusions Both PUS‐CNB and EUS‐FNA are safe and effective methods for the diagnosis of benign and malignant pancreatic lesions and have high clinical values . Reasonable selection of EUS‐FNA and PUS‐CNB can safely and reliably identify and diffentiate the benign and malignant pancreatic lesions .

Objective: To explore the safety and clinical value of percutaneous ultrasound-guided core needle biopsy(PUS-CNB) and endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) in pancreas mass. Methods: Ultrasound-guided biopsy were performed in 109 cases who were difficult to diagnose to get specimens from the highly suspicious parts of the lesions by avoiding vessels. PUS-CNB were performed in 82 cases, EUS-FNA in 19 cases and both in 8 cases. The site and size of lesions were recorded preopeartion. Specimens with clear pathological diagnosis were considered as satisfactory materials. Specimens that were impossible to puncture due to the existence of high risk factors in the process of puncture were considered as unsuccessful biopsy. All patients were followed up after biopsy and complications were recorded. Results: The satisfaction rate and success rate of PUS-CNB were 98.89% and 100%, the diagnostic accuracy and false negative rate were 97.78% and 2.22%. The satisfaction rate and success rate of EUS-FNA were 96.15% and 96.30%, the diagnostic accuracy and false negative rate were 80.77% and 23.81%. There were no serious complications such as pancreatic fistula, hemorrhage and needle transfer at the needle site after puncture. Conclusions Both PUS-CNB and EUS-FNA are safe and effective methods for the diagnosis of benign and malignant pancreatic lesions and have high clinical values. Reasonable selection of EUS-FNA and PUS-CNB can safely and reliably identify and diffentiate the benign and malignant pancreatic lesions.

Objective To assess the therapeutic efficacy of subcutaneous transplantation pancreatic cancer in nude mice model with different size microbubbles. Methods Eighteen Balb/C nude mice with subcutaneous pancreatic carcinoma xenografts were divided into three groups:group A( 6 mice) did not received microbubbles and ultrasonic irradiation;group B(6 mice) received standard microbubbles and ultrasonic cavitation treatment;group C(6 mice) received up-sized microbubbles and ultrasonic cavitation treatment.Body weight and tumor size of nude mice were measured respectively at the time points of 0,7, 14,21 days after three times ultrasound radiation and before ultrasound treatment. Tumor volumes were calculated.Then the mice were sacrificed finally. Results There was no significant difference in tumor volumes among three groups before treatment( P > 0.05). Tumor volume continued to increase in all groups.Compared with group A,growth rate in group B and group C were lower,growth rate in group B was higher than that in group C,the difference was statistically significant( P < 0.05). There was no significant difference in the parameters of regional blood volume(RBV) and regional blood flow(RBF)among three groups before treatment( P > 0.05). RBV and RBF were decreased significantly after 3 days treatment in group B and group C( P <0.05),the RBV and RBF in group C were lower than those in group B,the differences were statistically significant( P <0.05).There was no significant difference in the body weight of nude mice before and after radiation among three groups during the follow-up period( P >0.05). Conclusions The cavitation effect of up-sized microbubbles is more efficient for mice subcutaneous pancreatic cancer xenograft tumor inhibition compared with standard microbubbles.

Objective: To evaluate the diagnostic value of BRAF V600E mutation combined with shear wave elastography(SWE) for thyroid nodules of Bethesda Ⅲ diagnosed by fine-neddle aspiration(FNAC). Methods: One hundred and seventeen thyroid nodules diagnosed as Bethesda Ⅲ in the department of ultrasound and confirmed by BRAF V600E gene detection, SWE examination and surgery were collected. BRAF V600E detection, SWE examination and both combined with pathological results were using to retrospective analysis. Results: There were 75 benign nodules and 42 malignant nodules according to pathology. Sensitivity and negative predictive value of BRAF V600E combined with SWE were higher than single BRAF V600E mutation detection and SWE with statistically significant(P=0.01, 0.001; P=0.029, 0.01, respectively). There were no statistically differences between single BRAF V600E mutation detection and SWE for Bethesda Ⅲ nodules(P=0.483, 0.645). Conclusions BRAF V600E mutation detection combined with SWE can improve the sensitivity and negative predictive value in the diagnosis of Bethesda Ⅲ thyroid nodules.

Objective To determine whether low frequency ultrasound mediated microbubbles destruction (UMMD) could inhibit VX2 orthotopic hepatic tumor growth in rabbit models.Methods Twenty-four New Zealand white rabbits were implanted with VX2 tumor in left hepatic lobe to establish a homograft rabbit model of liver neoplasms in situ,which were randomly divided into four groups(6 rabbits in each group):group A (intravenous saline only),group B (intravenous microbubbles only),group C (intravenous saline+ low frequency focused ultrasound exposure),and group D (intravenous microbubbles+low frequency focused ultrasound exposure).After 3 days consecutive treatment,tumor volume(TV),and peak intensity (PI) were monitored by conventional ultrasound and contrast enhanced ultrasound(CEUS) on 0,1,7,14 and 21 days after treatment.The rabbits were euthanized at the end of the experiment.Tumor tissues were evaluated by HE stain.Results The parameters of TV and PI of each tumor had no significant difference among four groups before treatment(all P>0.05).TV had no significant difference among four groups on 1 day after treatment(all P>0.05);PI in group C and group D were significantly lower than those in group A and group B (all P<0.05).TV and PI in group D were significantly smaller than those in other groups on 7,14,21 days after treatment(all P<0.05).There was no statistical difference in TV and PI among group A,group B and group C(all P>0.05).The pathological changes of necrosis tissue,hemorrhagic damage of microvessel and thrombosis were observed in the tumors of group D only,whereas these changes occurred rarely in other groups.Conclusions UMMD can inhibit the growth of VX2 hepatic tumors in rabbits,and be used as a promising novel therapeutic strategy to liver neoplasms.

Objective To evaluate the clinical value of contrast-enhanced ultrasound (CEUS) in predicting peripancreatic vascular invasion in pancreatic carcinoma through comparison with the findings on surgical exploration. Methods A total of 94 pancreatic cancer patients (confirmed by pathological examination) were included in this study. The CEUS data were analyzed retrospectively. The enhancement characteristics of lesions were documented. And the peripancreatic vascular invasion were analyzed. The main features of peripancreatic vascular invasion on CEUS were as followings: 1) peripancreatic arteries to be embedded, trapped in the tumor or surrounded by tumor, or to have intraluminal infiltration or luminal stenosis. 2)superior mesenteric vein, portal vein to be surrounded by tumor or to be narrow, distorted or occluded. The CEUS findings were compared with postoperative pathological results. Results 94 patients were diagnosed with pancreatic cancer by pathological examination, including 62 cases of pancreatic head carcinoma, 32 cases of pancreatic tail carcinoma. The imaging of contrast-enhanced ultrasound showed 6 cases (6.4%) of high uneven enhancement, 78 cases (83%) of low uneven enhancement, and 10 cases (10.6%) of heterogeneous enhancement in parenchyma phase, respectively. Twenty-five cases (26.6%) of CA invasion were detected by CEUS, while no invasion was observed in 69 cases (73.4%). Compared with pathological findings, the predictive sensitivity, accuracy, specificity, positive predictive value, negative predictive value of CEUS were 63.6%, 79.7%, 84.7%, 56.0%, 88.0%, respectively. Twenty-seven cases (28.7%) of SMA invasion were detected by CEUS, while no invasion were observed in 67 cases (71.3%). Compared with pathological findings, the predictive sensitivity, accuracy, specificity, positive predictive value, negative predictive value of CEUS were 66.6%, 77.6%, 80.2%, 44.0%, 91.0%, respectively. Besides, PV invasion features were found in 27 cases (28.7%), while 67(71.3%) cases were detected without invasion features. Compared with pathological findings, sensitivity, accuracy, specificity, positive predictive value, negative predictive value of CEUS in predicting PV invasion were 86.6%, 94.6%, 98.4%, 96.2%, 94.0%, respectively. Furthermore, CEUS detected SMV invasion in 26 cases (27.6%), while no invasion features in 68 (72.4%) cases. The sensitivity, accuracy, specificity, positive predictive value, negative predictive value for CEUS were 75.0%, 87.2%, 92.4%, 80.7%, 89.7%, respectively. Conclusion Due to its good diagnostic and predictive performance in detecting malignant pancreatic tumors and peripancreatic vascular invasion, CEUS could be served as an effective predictive modality in assessing the resectability of pancreatic carcinoma.

Objective To evaluate the diagnostic value of puncture feeling combined with fine-needle aspiration cytology (FNAC) for thyroid nodules.Methods One thousand and fourteen thyroid nodules were retrospectively analyzed.Eighty-six thyroid nodules were performed repeat FNAC.All nodules were confirmed by pathology,the agreement of puncture feeling at different time was evaluated by Kappa test.Results There were 751 malignant nodules and 263 benign nodules.Sensitivity and accuracy of FNAC combined with puncture feeling were higher than those of single FNAC or single puncture feeling (x2 =11.609,4.433 and P =0.00,0.04;x2 =19.369,6.697 and P =0.00,0.01,respectively).There were no statistically differences in the sensitively and accuracy between single FNAC and puncture feeling (x2 =1.230,0.242 and P =0.27,0.62,respetively).The Kappa values of inter-observer and intra-observer were 0.829(P =0.00) and 0.885(P =0.00) respectively with statistically significance.Conclusions Puncture feeling combined with FNAC can improve the sensitivity and accuracy in the diagnosis of thyroid nodules,the reproducibility of puncture feeling is excellent.

Objective To evaluate the association of the size of thyroid nodules and the diagnostic value of repeat fine needle aspiration cytology(FNAC) in diagnose of thyroid nodules.Methods One hundred and forty-three thyroid nodules in one hundred and thirty-five patients with repeat FNAC and thyroidectomy were retrospectively analyzed.The nodules were divided into three groups according to the largest diameter(L):GroupA,L＜0.5 cm;GroupB,0.5 cm≤L≤1.0cmandGroupC,L＞1.0cm.Yield of FNACs were divided into six levels according to the classification criteria of the Bethesda system,and Level Ⅰ,Ⅲ,Ⅳ,Ⅴ were defined as the indefinite cytological diagnosis.Results The diagnostic rate of repeat FNAC was obviously higher in group B compared with group A and group C,with significantly statistical difference (P ＜0.05).The risk of malignancy for persistently indefinite diagnostic aspirates after repeat FNAC was significantly reduced with statistical difference from the initial indefinite diagnostic aspirates in group B (P ＜0.05),while there was no statistical difference between group A and group C (P＞0.05).The diagnostic accuracy of repeat FNAC in group B was significantly higher than that in group A(P ＜0.05),but not in group C (P ＜0.05).Conclusions The repeat FNAC has a higher efficiency in those nodules with a largest diameter between 0.5 cm and 1.0 cm,and a repeat FNAC can be suggested.