Objective:To investigate the clinical manifestations, pathological features, and genetic variant characteristics of children with glycogen storage disease type Ⅸa (GSD Ⅸa).Methods:A retrospective case series analysis was conducted to collected and analyzed the medical history, biochemical markers, liver ultrasound results, liver histopathological findings, genotypes, treatment regimens, and follow-up data of 4 pediatric patients diagnosed with GSD IXa in the Department of Infectious Diseases at Xiamen Children′s Hospital from January 2018 to May 2024. All patients were confirmed by genetic testing.Results:All 4 pediatric patients diagnosed with GSD Ⅸa were male. The ages of onset were 8 months, 2 years, 3 years and 3 months, 1 year and 5 months, respectively, with initial presentations including chronic diarrhea (Case 1), incidentally detected transaminase elevation during routine examinations (Cases 2 and 3), and delayed motor development (Case 4). Diagnosis was confirmed at ages 10 months, 3 years, 3 years 4 months and 1 year 6 months, respectively.At diagnosis, anthropometric parameters and biochemical profiles revealed:Height: 68 cm (< P3), 96 cm ( P25-50), 94 cm ( P3-10), and 94 cm ( P3-10).Weight: 7 kg (< P3), 17 kg ( P90-97), 14.4 kg ( P25-50), and 10.5 kg ( P25-50).Alanine aminotransferase: 299, 500, 271, and 313 U/L (reference range 0-40 U/L).Aspartate aminotransferase: 285, 543, 337 and 357 U/L (reference range 0-40 U/L).Fasting glucose: 2.80, 3.67, 2.98, and 3.66 mmol/L (reference range 3.90-6.10 mmol/L).Lactate: 4.3, 2.1, 1.3, and 2.6 mmol/L (reference range 0.5-2.2 mmol/L).Triglycerides: 5.22, 1.38, 1.32, and 1.88 mmol/L (reference range 0.56-1.70 mmol/L).Case 1 exhibited poor adherence to uncooked cornstarch therapy during initial treatment, with no significant improvement in biochemical parameters. Follow-up imaging at age 4 revealed hepatic adenoma. Subsequent improvement in therapeutic compliance led to biochemical normalization, reduced hepatic adenoma size, and growth parameters of 113 cm ( P10-25) and 26 kg ( P90-97) at 6 years 2 months. Cases 2-4 demonstrated biochemical improvement with regular uncooked cornstarch therapy and no evidence of hepatic adenoma.Liver histopathology in Cases 1-3 confirmed glycogen accumulation consistent with GSD, without cirrhotic changes. Genetic analysis identified PHKA2 variations in all cases: 2 missense variants, 1 frameshift variant and 1 nonsense variant. The c.2839dup and c.3267G>A variants represent novel pathogenic mutations. Conclusions:GSD Ⅸa in pediatric patients is predominantly characterized by hepatomegaly, hepatic dysfunction, and hypoglycemia. While uncooked cornstarch therapy typically yields favorable prognoses, a subset of patients may develop hepatic adenomas. Notably, children with hepatic adenoma exhibited younger age of onset, significant growth retardation, and more severe metabolic disturbances, suggesting that hepatic adenoma development may be closely linked to the severity of metabolic dysregulation.

Objective To investigate the effects of Danlong Xingnao Prescription on learning and memory ability and microglia activation in rats with vascular dementia(VD)based on HMGB1/RAGE/NF-κB pathway.Methods Ten rats were randomly selected from 72 rats as a sham-operation group.The remaining rats were treated with modified bilateral common carotid artery ligation method to prepare the VD model.The 50 successful model rats were randomly divided into model group,nimodipine group(10.8 mg/kg)and Danlong Xingnao Prescription low-,medium-and high-dosage groups(3.7,7.4,14.8 g/kg),with 10 rats in each group.The administration groups were given relevant solution for gavage,the sham-operation group and model group were given the same amount of normal saline for consecutive 28 d.Morris water maze test was performed to evaluate learning and memory abilities of rats,the morphology in the hippocampus were observed by HE staining,the contents of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α in hippocampal tissue were detect by ELISA,RT-PCR was used to detect high mobility group protein B1(HMGB1),receptor of advanced glycation end product(RAGE),nuclear factor(NF)-κB p65 and regulatory RNase-1(Regnase-1)mRNA expression in hippocampal tissue,immunohistochemistry and Western blot were used to detect the protein expressions of ion calcium binding adapter molecule 1(Iba1),HMGB1,RAGE,NF-κB p65 and Regnase-1 in hippocampal tissue.Results Compared with the sham-operation group,the escape latency of rats was prolonged,and the number of crossings through the original platform was increased in the model group(P<0.01),the pyramidal cells in the hippocampus were reduced and irregularly shaped,with unclear cell and nuclear membranes,and a significant number of necrotic neurons were visible,the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue increased(P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue increased(P<0.01),while the mRNA expression of Regnase-1 decreased(P<0.01),the protein expressions of Iba1,HMGB1,RAGE and NF-κB p65 increased(P<0.01),while the protein expression of Regnase-1 decreased(P<0.01).Compared with the model group,the escape latency of rats was shortened in Danlong Xingnao Prescription groups,the number of crossings through the original platform was reduced(P<0.05,P<0.01),the neuronal structure of hippocampal tissue was significantly improved,the number of necrotic neurons was reduced,and the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue reduced(P<0.05,P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue decreased,the mRNA expression of Regnase-1 increased(P<0.05,P<0.01),the protein expression of Iba1,HMGB1,RAGE and NF-κB p65 decreased,the protein expression of Regnase-1 increased(P<0.05,P<0.01).Conclusion Danlong Xingnao Prescription can improve the learning and memory ability of VD rats,and its mechanism may be related to inhibiting the activation of HMGB1/RAGE/NF-κB pathway and increasing Regnase-1 expression,thereby inhibiting the activation of microglia.

Objective To investigate the effects of Danlong Xingnao Prescription on learning and memory ability and microglia activation in rats with vascular dementia(VD)based on HMGB1/RAGE/NF-κB pathway.Methods Ten rats were randomly selected from 72 rats as a sham-operation group.The remaining rats were treated with modified bilateral common carotid artery ligation method to prepare the VD model.The 50 successful model rats were randomly divided into model group,nimodipine group(10.8 mg/kg)and Danlong Xingnao Prescription low-,medium-and high-dosage groups(3.7,7.4,14.8 g/kg),with 10 rats in each group.The administration groups were given relevant solution for gavage,the sham-operation group and model group were given the same amount of normal saline for consecutive 28 d.Morris water maze test was performed to evaluate learning and memory abilities of rats,the morphology in the hippocampus were observed by HE staining,the contents of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α in hippocampal tissue were detect by ELISA,RT-PCR was used to detect high mobility group protein B1(HMGB1),receptor of advanced glycation end product(RAGE),nuclear factor(NF)-κB p65 and regulatory RNase-1(Regnase-1)mRNA expression in hippocampal tissue,immunohistochemistry and Western blot were used to detect the protein expressions of ion calcium binding adapter molecule 1(Iba1),HMGB1,RAGE,NF-κB p65 and Regnase-1 in hippocampal tissue.Results Compared with the sham-operation group,the escape latency of rats was prolonged,and the number of crossings through the original platform was increased in the model group(P<0.01),the pyramidal cells in the hippocampus were reduced and irregularly shaped,with unclear cell and nuclear membranes,and a significant number of necrotic neurons were visible,the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue increased(P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue increased(P<0.01),while the mRNA expression of Regnase-1 decreased(P<0.01),the protein expressions of Iba1,HMGB1,RAGE and NF-κB p65 increased(P<0.01),while the protein expression of Regnase-1 decreased(P<0.01).Compared with the model group,the escape latency of rats was shortened in Danlong Xingnao Prescription groups,the number of crossings through the original platform was reduced(P<0.05,P<0.01),the neuronal structure of hippocampal tissue was significantly improved,the number of necrotic neurons was reduced,and the contents of IL-1β,IL-6 and TNF-α in hippocampal tissue reduced(P<0.05,P<0.01),the mRNA expressions of HMGB1,RAGE and NF-κB p65 in hippocampal tissue decreased,the mRNA expression of Regnase-1 increased(P<0.05,P<0.01),the protein expression of Iba1,HMGB1,RAGE and NF-κB p65 decreased,the protein expression of Regnase-1 increased(P<0.05,P<0.01).Conclusion Danlong Xingnao Prescription can improve the learning and memory ability of VD rats,and its mechanism may be related to inhibiting the activation of HMGB1/RAGE/NF-κB pathway and increasing Regnase-1 expression,thereby inhibiting the activation of microglia.

Objective:To investigate the clinical manifestations, pathological features, and genetic variant characteristics of children with glycogen storage disease type Ⅸa (GSD Ⅸa).Methods:A retrospective case series analysis was conducted to collected and analyzed the medical history, biochemical markers, liver ultrasound results, liver histopathological findings, genotypes, treatment regimens, and follow-up data of 4 pediatric patients diagnosed with GSD IXa in the Department of Infectious Diseases at Xiamen Children′s Hospital from January 2018 to May 2024. All patients were confirmed by genetic testing.Results:All 4 pediatric patients diagnosed with GSD Ⅸa were male. The ages of onset were 8 months, 2 years, 3 years and 3 months, 1 year and 5 months, respectively, with initial presentations including chronic diarrhea (Case 1), incidentally detected transaminase elevation during routine examinations (Cases 2 and 3), and delayed motor development (Case 4). Diagnosis was confirmed at ages 10 months, 3 years, 3 years 4 months and 1 year 6 months, respectively.At diagnosis, anthropometric parameters and biochemical profiles revealed:Height: 68 cm (< P3), 96 cm ( P25-50), 94 cm ( P3-10), and 94 cm ( P3-10).Weight: 7 kg (< P3), 17 kg ( P90-97), 14.4 kg ( P25-50), and 10.5 kg ( P25-50).Alanine aminotransferase: 299, 500, 271, and 313 U/L (reference range 0-40 U/L).Aspartate aminotransferase: 285, 543, 337 and 357 U/L (reference range 0-40 U/L).Fasting glucose: 2.80, 3.67, 2.98, and 3.66 mmol/L (reference range 3.90-6.10 mmol/L).Lactate: 4.3, 2.1, 1.3, and 2.6 mmol/L (reference range 0.5-2.2 mmol/L).Triglycerides: 5.22, 1.38, 1.32, and 1.88 mmol/L (reference range 0.56-1.70 mmol/L).Case 1 exhibited poor adherence to uncooked cornstarch therapy during initial treatment, with no significant improvement in biochemical parameters. Follow-up imaging at age 4 revealed hepatic adenoma. Subsequent improvement in therapeutic compliance led to biochemical normalization, reduced hepatic adenoma size, and growth parameters of 113 cm ( P10-25) and 26 kg ( P90-97) at 6 years 2 months. Cases 2-4 demonstrated biochemical improvement with regular uncooked cornstarch therapy and no evidence of hepatic adenoma.Liver histopathology in Cases 1-3 confirmed glycogen accumulation consistent with GSD, without cirrhotic changes. Genetic analysis identified PHKA2 variations in all cases: 2 missense variants, 1 frameshift variant and 1 nonsense variant. The c.2839dup and c.3267G>A variants represent novel pathogenic mutations. Conclusions:GSD Ⅸa in pediatric patients is predominantly characterized by hepatomegaly, hepatic dysfunction, and hypoglycemia. While uncooked cornstarch therapy typically yields favorable prognoses, a subset of patients may develop hepatic adenomas. Notably, children with hepatic adenoma exhibited younger age of onset, significant growth retardation, and more severe metabolic disturbances, suggesting that hepatic adenoma development may be closely linked to the severity of metabolic dysregulation.

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 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 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.