1.The Effect of Zhiqiao Gancao Decoction (枳壳甘草汤) on Intervertebral Disc Nucleus Pulposus Cell Apoptosis and the Hippo-YAP/TAZ Signaling Pathway in Tail Intervertebral Disc Degeneration Model Rats
Zaishi ZHU ; Zeling HUANG ; Junming CHEN ; Bo XU ; Binjie LU ; Hua CHEN ; Xingxing DUAN ; Yuwei LI ; Xiaofeng SHEN
Journal of Traditional Chinese Medicine 2025;66(5):509-517
ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction (枳壳甘草汤, ZGD) delays intervertebral disc degeneration (IDD) based on the Hippo-yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group, model group, low-dose ZGD group, high-dose ZGD group, and high-dose ZGD + inhibitor group, with 10 rats in each group. In the sham surgery group, the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle (depth approximately 2 mm) without damaging the intervertebral disc. In the other groups, rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling, rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/(kg·d) of the decoction via gastric gavage, respectively. The high-dose ZGD + inhibitor group was given 12.24 g/(kg·d) of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/(kg·d) of normal saline via gavage. The gavage was given once a day, and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention, the pathological changes of the tail intervertebral discs were observed using HE staining, Oil Red O-Green staining, and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus, and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway, including YAP, phosphorylated YAP (p-YAP), phosphorylated MST1/2 (p-MST1/2), phosphorylated TAZ (p-TAZ) and apoptosis-related proteins, such as Cleaved Caspase 3, P53, Bcl-2 and Bax. ResultsCompared with sham surgery group, the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan, Bcl-2, and YAP proteins in the nucleus pulposus decreased, while the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and the apoptosis rate increased (P < 0.01). Compared with the model group, the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan, Bcl-2, and YAP proteins increased, while the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and the apoptosis rate decreased (P<0.05 or P<0.01). The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group, with a decrease in the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and apoptosis rate, and an increase in the levels of aggrecan, Bcl-2, and YAP proteins (P<0.05 or P<0.01). Compared with the high-dose ZGD group, the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration, with an increase in the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and apoptosis rate, and a decrease in the levels of aggrecan, Bcl-2, and YAP proteins (P<0.05 or P<0.01). ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus, maintaining the function of the Hippo-YAP/TAZ signaling pathway, and reducing apoptosis of nucleus pulposus cells.
2.Establishment of whole-process intelligent pharmaceutical care model for peritoneal dialysis patients
Yongfu HANG ; Yan XU ; Xiaohua DAI ; Tiantian WU ; Yinyin DUAN ; Deyu XU ; Kun HU ; Xingxing LIU ; Jianguo ZHU ; Liyan MIAO ; Lin LI
China Pharmacy 2023;34(21):2644-2648
OBJECTIVE To develop a whole-process intelligent model of pharmaceutical care for peritoneal dialysis (PD) patients, and to provide a reference for clinical pharmacists to provide standardized PD pharmaceutical care. METHODS The pharmaceutical care mode of PD patients at home and abroad was investigated and analyzed. Based on the actual situation of the First Affiliated Hospital of Soochow University (hereinafter referred to as “our hospital”), with “home→PD center outpatient→ inpatient department” as the main node, the recycling process of medication reconciliation was optimized. The whole-process intelligent pharmaceutical care model of PD was illustrated by improving the Chinese version of the drug-related problems (DRPs) classification tool, developing the corresponding pharmaceutical care process, and presenting specific cases. RESULTS Based on the medication therapy management (MTM) platform, our hospital had built a closed-loop PD whole-process intelligent pharmaceutical care model of “in-hospital pharmaceutical care (building document)-PD outpatient MTM-home pharmaceutical care (online App management)”. A “double cycle” workflow of “admission→discharge→outpatient” medication reconciliation cycle and “discovery-analysis-intervention-follow-up-record-evaluation” DRPs cycle was formed. CONCLUSIONS The establishment of the whole-process intelligent pharmaceutical care model for PD in our hospital provides experience for standardizing pharmaceutical care for PD patients, and can reduce DRPs.
3.Pilot study of artificial intelligence ultrasound diagnosis of biliary atresia based on deep learning
Liu YANG ; Chun DU ; Wenjuan CHEN ; Xingxing DUAN ; Mengjie ZHOU ; Huan WEN
Chinese Journal of Ultrasonography 2021;30(5):402-407
Objective:To explore the feasibility of artificial intelligence ultrasound to diagnose of biliary atresia (BA) based on deep learning.Methods:A total of 531 gallbladder ultrasound images in 177 cases of BA patients (BA group) and 585 gallbladder ultrasound images in 195 cases of Non-BA patients (Non-BA group) were collected in Hunan Children′s Hospital from September 2018 to October 2020. For the BA and Non-BA groups, all images were divided into training set and test set according to the ratio of 2∶1. The Mask R-CNN model was trained by training samples, and then the model was tested, according to patient and image as a unit respectively, to evaluate the gallbladder organ detection rate and the diagnostic accuracy of BA. In addition, the images of the test set were randomly numbered.Four sonographers were invited to interpret the images to calculate the diagnostic accuracy individually. Last, the diagnostic accuracy of the Mask R-CNN model was compared with that of sonographers.Results:In terms of the automatic detection of gallbladder organs, the detection rate in both BA and Non-BA group reached 100%, but there were 17 false alarms in 372 test images, with a false alarm rate of 4.57%. In terms of the diagnostic rate of gallbladders, when taking patient as a unit, the total diagnostic accuracy of the model in the test set was 95.97%, which was higher than that of the sonographers in other hospitals and the sonographer with intermediate professional title in our hospital, and the difference was statistically significant ( P<0.005). It was slightly higher than that of sonographer with senior professional title in our hospital (91.94%), but the difference was not statistically significant ( P=0.183). When taking picture as a unit, the total diagnostic accuracy of the model was 97.04%, which was higher than that of the sonographers in other hospitals and the sonographer with intermediate professional title in our hospital, and the difference was statistically significant ( P<0.001). It was slightly higher than that of sonographer with senior professional title in our hospital (94.09%), but the difference was not statistically significant ( P=0.05). Conclusions:The artificial intelligence technology based on Mask R-CNN can automatically and accurately detect gallbladder organs and diagnose BA, which is worthy of further study.
4.Evaluation of right ventricular-pulmonary artery coupling in patients with acute pulmonary embolism by the ratio of tricuspid annular plane systolic excursion and tricuspid regurgitation pressure gradient
Xin DUAN ; Wenqian SHEN ; Shuang WANG ; Shuang CHEN ; Haiyuan YU ; Xingxing REN ; Qiqi LIU ; Zeya SUN ; Guoqing DU
Chinese Journal of Ultrasonography 2021;30(11):982-987
Objective:To evaluate the feasibility of a new ultrasonic parameter to assess right ventricular-pulmonary artery (RV-PA) coupling in patients with acute pulmonary embolism (APE).Methods:A retrospective analysis was performed in 140 patients with APE diagnosed by computed tomography pulmonary angiography (CTPA) in the Second Affiliated Hospital of Harbin Medical University from August 2017 to June 2020. According to the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio cutoff value 0.40 mm/mmHg reported by the European Society of Cardiology in 2020, the patients were divided into the coupling group ( n=99) and the uncoupling group ( n=41). The conventional ultrasonic parameters of the 2 groups were measured, and then several ultrasonic parameter ratios were obtained. The new ultrasonic parameter, which can replace the TAPSE/PASP ratio, was screened out by Spearman correlation analysis, and ROC curve was plotted to calculate the diagnostic efficacy of this parameter. Results:①Compared with the coupling group, patients in the uncoupling group were older and more likely to be accompanied by dyspnea and venous thrombosis in the lower extremities (all P<0.05), but there was no significant difference in other general data(all P>0.05); ②Compared with the coupling group, tricuspid regurgitation velocity (TRV), tricuspid regurgitation pressure gradient(TRPG), PASP, right ventricle end-diastolic transverse diameter(RVTD), inferior vena cava(IVC) diameter and the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity(E/e′), in the uncoupling group increased significantly (all P<0.05), and TAPSE, peak systolic velocity of tricuspid annulus(s′), TAPSE/PASP ratio, TAPSE/TRPG ratio, TAPSE/RVTD ratio and s′/TRPG ratio decreased significantly (all P<0.05); ③The TAPSE/TRPG ratio was highly correlated with TAPSE/PASP ratio ( rs=0.970, P<0.001); The TAPSE/TRPG ratio was still highly correlated with TAPSE/PASP ratio in the uncoupling and coupling groups ( rs=0.966, 0.922; all P<0.001). ④ROC analysis showed that the area under curve for TAPSE/TRPG in diagnosing RV-PA coupling was 0.992. At the cutoff of TAPSE/TRPG <0.625 mm/mmHg for indicating RV-PA coupling, the sensitivity and specificity were 97.6% and 92.9%, respectively. Conclusions:TAPSE/TRPG ratio can be used as a new ultrasonic parameter to reflect RV-PA coupling, which is helpful for clinical identification of APE patients with high risk and poor prognosis.
5.Value of shear wave elastography for the evaluation of hepatics fibrosis in infants with biliary atresia before Kasai portoenterostomy
Xingxing DUAN ; Ya PENG ; Liu YANG ; Weijian CHEN ; Wenjuan CHEN
Chinese Journal of Ultrasonography 2020;29(2):143-148
Objective:To investigate the application value of shear wave elastography(SWE) in assessing the degree of hepatics fibrosis in children with biliary atresia before Kasai portoenterostomy.Methods:From January 2017 to January 2018, 49 cases of children in Hunan Children′s Hospital with highly suspected biliary atresia in clinical were collected. The stiffness of the lower segment of right anterior lobe of the liver in all cases was assessed using SWE in 3 days before Kasai portoenterostomy. Pathological results of liver tissue specimens from the lower edge of the right liver during the surgery was taken as the gold standard. The correlation between the liver stiffness and the hepatics fibrosis was analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curves were created to assess the area under curve (AUC), the best cutoff value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the liver stiffness in diagnosing hepatocirrhosis.Results:All of the 49 cases were confirmed by surgery and pathology. According to the stages of hepatics fibrosis, 5 cases were in stage S2, 23 cases in stage S3, 21 cases in stage S4, and no cases of stage S0 and S1. Spearman correlation analysis showed that the correlation coefficient between the liver stiffness and the stages of hepatics fibrosis was 0.779( P<0.001). The area under the curve of the liver stiffness in diagnosing cirrhosis was 0.914. When the cutoff value was 14.45 kPa, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 85.7%, 89.3%, 85.7%, 89.3%, 87.8%, respectively. Conclusions:The liver stiffness measured by SWE is positively correlated with the stages of hepatic fibrosis, and the performance of SWE in the diagnosis of cirrhosis is remarkable. SWE can be used to evaluate the stages of hepatics fibrosis in children with biliary atresia before Kasai portoenterostomy.
6.Application of the moving epidemic method in the development of epidemic thresholds and tiered warning alert approachs for influenza prevention in Beijing
Yu WANG ; Li ZHANG ; Shuangsheng WU ; Wei DUAN ; Ying SUN ; Man ZHANG ; Xingxing ZHANG ; Yi ZHANG ; Chunna MA ; Quanyi WANG ; Peng YANG
Chinese Journal of Epidemiology 2020;41(2):201-206
Objective To calculate both the epidemic and intensity thresholds for different levels in Beijing and to establish a tiered alert system in the 2018-2019 influenza season as well as to evaluate the performance of calculated thresholds.Method Weekly count of influenza-like illness and percentage of influenza-like illness (ILI%) of the last five influenza seasons were modeled by 'moving epidemic method'(MEM) to calculate the influenza epidemic and intensity thresholds at different levels.A cross-validation procedure was used to evaluate the performance.Indicators of Matthew correlation coefficient,Youden's index,sensitivity and specificity were calculated.Results For weekly count of influenza-like illness,data showed that the epidemic threshold for 2018-2019influenza season was 12 984 and the medium,high and very high intensity thresholds were 22 503,37 589,47 157,respectively.Matthew correlation coefficient of the epidemic threshold was 62% and youden's index as 60%,sensitivity as 69%,specificity as 91%.Data on weekly ILI%,the epidemic threshold for 2018-2019 influenza season was 1.66%,with medium,high and very high intensity thresholds as 2.46%,3.84% and 4.66%,respectively.The overall Matthew correlation coefficient of the epidemic threshold was 59%,with 54% for the Youden's index,sensitivity as 60% and specificity as 94%.Conclusions MEM produced a good specific signal for detecting the influenza epidemics and the accuracy of the method was acceptable.The early warning performance regarding the application of weekly count on influenza-like illness was slightly better than ILI%.This method could be applied in the practical influenza epidemic alert "work in Beijing".
7.Application of echocardiography Z score in pediatric dilated cardiomyopathy
Limiao XIAO ; Wenjuan CHEN ; Xingxing DUAN ; Yuan HU ; Qianjun LIU ; Wenfang YUAN
Chinese Journal of Medical Imaging Technology 2018;34(1):144-148
The children with dilated cardiomyopathy (DCM) are in the different stages of growth and development,so the measurements of the cardiac size and the function in the echocardiography can change with those growth and development.But the influence factors of growth and development had been ignored by the previous standards,which was not conducive to evaluate the efficacy of drugs and the prognosis of patients.The disadvantages above can be overcome by converting the echocardiographic measurements into the Z score after correction of the body surface area.With the development of the ultrasonic technology,there have been some studies of the Z score combined with the ultrasound to assess the left/right ventricular heart function and prognosis in children with dilated cardiomyopathy.The progresses of Z score in children with dilated cardiomyopathy were reviewed in this article.
8.Abdominal ultrasonographic manifestations of Langerhans cells histiocytosis in children
Jie ZHANG ; Wenjuan CHEN ; Huixian MENG ; Yuan HU ; Xingxing DUAN
Chinese Journal of Medical Imaging Technology 2018;34(6):884-887
Objective To observe the abdominal ultrasonic manifestations of children with Langerhans cells histiocytosis (LCH).Methods Imaging features of histopathologically proved LCH in 28 children were retrospectively analyzed.Results Among 28 eases,multi system involvement was found in 25 cases,while only liver and bile duct involvement were detected in 3 cases.Different degrees of enlarged liver,inhomogeneous echo of liver parenchyma,scattered or diffuse hypoechoic regions were found in all 28 cases.Uneven thickening and echo enhancement of the bile duct wall,as well as local expansion or stricture of bile duct cavity were found in 13 cases.Splenomegaly was found in 17 cases,swelling of the pancreas was found in 5 cases,varying degrees of ascites were found in 13 cases,and hepatic hilar lymphadenectasis were found in 14 cases.Conclusion There are specific ultrasonographic manifestations of LCH in children,which may be helpful to improving diagnostic accuracy of LCH.
9.Value of real time shear wave elastography in the antidiastole of biliary atresia in infants within 60 days
Xingxing DUAN ; Taoyue YAO ; Ya PENG ; Hao LI ; Jie ZHANG
Chinese Journal of Ultrasonography 2018;27(2):151-154
Objective To investigate the value of shear wave elastography (SWE) in the differential diagnosis of biliary atresia (BA) in infants within 60 days.Methods SWE was used to detect the hepatic Young's modulus of 85 infants within 60 days who were suspected with cholestatic hepatitis.All the patients were classified into BA group and non biliary atresia (Non-BA) group according to surgical or pathological results.At the same time,45 normal infants within 60 days were selected as the control group.The hepatic Young's modulus were compared among the 3 groups.The sensitivity and specificity of hepatic Young's modulus in suspected BA patients were calculated by ROC.Results In the 85 cases,42 cases were diagnosed as BA,and 43 cases were classified as Non-BA group.The Young's modulus values of the 3 groups were as follows:BA group (15.86 ± 5.89) kPa,Non-BA group (10.89 ± 2.38) kPa,and control group (6.64 ± 0.53)kPa,with a significant difference among the 3 groups(P <0.01).The ROC analysis showed a cut off value of 12.9 kPa for differentiation between BA group and Non-BA group.The area under ROC curve (AUROC) was 0.787,with a sensitivity of 59.5% and a specificity of 88.4%.Conclusions The young's modulus in BA patients can be increased at early time,and the SWE technique can be used to reflect the change of hepatic Young's modulus accurately,which will be helpful in the early differential diagnosis of BA.
10.Value of shear wave elastography in diagnosing biliary atresia by ultrasonography
Xingxing DUAN ; Ya PENG ; Lingping LIU ; Jie ZHANG ; Xiangfen XU ; Wenjuan CHEN
Chinese Journal of Ultrasonography 2018;27(11):942-947
Objective To investigate the value of the shear wave elastography ( SWE) in the diagnosis of biliary atresia ( BA ) in infants by ultrasonography . Methods SWE was used to measure the liver stiffness measurement( LSM ) of 138 infants . Following surgical or pathological diagnosis ,the infants were subclassified into BA and non-biliary atresia ( non-BA ) groups . ROC analysis was used to determine the sensitivity and specificity of LSM ,the ultrasonic findings in the differential diagnosis of suspected BA ,and the cut-off value to diagnose BA . Results Of the 138 infants with cholestatic hepatitis ,51 were diagnosed as BA group and 87 cases were assigned to the non-BA group . The ROC analysis showed the cut-off value of LSM for diagnosis of biliary atresia in children with jaundice was 12 .35 kPa ,the AUC was 0 .936 ,and the sensitivity and specificity were 84 .3% and 89 .7% ,respectively .In the parallel test ,the triangular cord ( TC) sign combined with abnormal gallbladder ( AbGB) had the best diagnostic performance in all patients . However ,in patients older than 30 days ,the LSM combined with TC had the best AUC ( 0 .987 ) and diagnostic performance( 98 .6% ) like with TC combined with AbGB . Conclusions Both SWE and gray scale ultrasound have higher diagnostic performance for BA . LSM can be used as a valuable index for diagnosing BA by ultrasound .

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