Objective To evaluate the role of c-Jun N-terminal kinase (JNK) signaling pathway in the protective effect of isoflurane preconditioning and sevoflurane preconditioning against oxygen-glucose deprivation (OGD) injury in rat hippocampal slices. Methods Male adult SD rats weighing 270-290 g were anesthetized with ether and decapitated. The hippocampi were removed and sagittally sliced (400 μm thick) and placed in artificial cerebral spinal fluid aerated with 95% O2-5% CO2 . Ninety-six hippocampal slices were randomly divided into 8 groups (n = 12 each): control group (group C), OGD group, isoflurane preconditioning group (group Iso),sevoflurane preconditioning group (group Sevo) , SP600125 + isoflurane preconditioning group (group SP + Iso),SP600125 +sevoflurane preconditioning group (group SP + Sevo), DMSO + isoflurane preconditioning group (group DMSO + Iso) and DMSO + sevoflurane preconditioning group (group DMSO + Sevo). Electrophysiological technique was used to record the amplitude of population spike ( PS) in the stratum pyramidale of CA1 region and the degree of recovery of PS was calculated. The cell viability was determined by propidium iodide staining. Results Compared with group C, the degree of recovery of PS and cell viability were significantly decreased in the other groups ( P ＜ 0.01) . Compared with group OGD, the degree of recovery of PS and cell viability were significantly increased in groups Iso, Sevo, SP+Iso, SP+Sevo, DMSO+ Iso and DMSO + Sevo (P＜ 0.01). Compared with group Iso, the degree of recovery of PS and cell viability were significantly increased in group SP+Iso ( P ＜ 0.01) , while no significant change was found in group DMSO + Iso ( P ＞ 0.05) . Compared with group Sevo, the degree of recovery of PS and cell viability were significantly increased in group SP + Sevo ( P ＜ 0.01) , while no significant change was found in group DMSO + Sevo ( P ＞ 0.05). Conclusion Isoflurane preconditioning and sevoflurane preconditioning can attenuate the OGD injury to rat hippocampal slices through inhibiting JNK signaling pathway.

Objective Using gradient-echo sampling of spin-echo (GESSE) sequence to study the change of oxygen extraction fraction (OEF) in patients with unilateral cerebral vessel stenosis and the relationship between OEF and cerebral blood flow (CBF). Methods Eight normal volunteers and 16 patients with unilateral cerebral vessel stenosis were enrolled in this study. Written informed consents were obtained from all subjects. Routine MRI, GESSE and arterial spin labeling (ASL) sequences were performed for all patients. Raw data from GESSE and VE-ASL sequences were transferred to PC to conduct postprocessing. To obtain quantitative OEF and CBF of the brain parenchyma, 6 ROIs were placed respectively in the anterior, middle and posterior part of both hemispheres. The relative CBF (rCBF) was defined as the ratio of CBF of ischemic hemisphere to that of contralateral hemisphere. T test was used for statistics. Results The mean value and normal range of OEF in the volunteers were 0. 318 ± 0. 023 and 0. 272-0. 364, respectively. In the 16 patients with unilateral cerebral vessel stenosis, 8 patients had ROIs with greater OEF in unilateral hemisphere than those in contralateral hemisphere. These cases presented multiple intracranial main arterial stenoses in digital subtraction angiography (DSA) or MR angiography (MRA) examination. The other 8 patients had normal OEF in all ROIs. And they only had single arterial stenosis in DSA or MRA. Set rCBF = 0. 50 as a dividing point, the mean OEF value was 0. 397 ±0. 010 in the patients with rCBF ＜ 0. 50. In the patients with rCBF ≥ 0. 5, the mean OEF value was 0. 325 ±0. 028. The difference between the two groups was statistically significant (t = - 8. 840, P = 0. 000).Conclusion Patients with chronic cerebral ischemia may present with various hemodynamic impairment.The more CBF decreases, the more OEF increases. Those with increased OEF tended to have more than one lesion in the major intracranial arteries.

The purpose of this study was to investigate and discuss imaging methods and management strategies for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies. In this study we reviewed and analyzed 72 patients with congenital choledochal cyst, ranging in age from 15 days to 12 years old and who were seen at our hospital during the past 12 years, from January 1993 to October 2005. The image manifestation and clinical significance of patients with co- xisting intrahepatic biliary dilation and aberrant bile duct were carefully examined during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of the cystic type. That is, the orifice of the dilated intrahepatic tract that converged into the common hepatic duct showed membrane or septum-like stenosis. In 10 cases the dilation tapered off from the porta hepatis to the initiating terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left hepatic ducts converged at the choledochal cyst. In conclusion, the imaging methods for intrahepatic bile duct dilation possess important clinical significance. Further, for hepatojejunostomy with radical excision of a choledochal cyst, additional operative procedures for intrahepatic stenosis, possible bile duct malformation and pancreaticobiliary common duct calculi can potentially reduce postoperative complications.
Tomography, X-Ray Computed ; Postoperative Complications/ultrasonography ; Male ; Liver Diseases/complications/*radiography/surgery ; Infant, Newborn ; Infant ; Humans ; Female ; Choledochal Cyst/complications/*radiography/surgery ; Cholangiography ; Child, Preschool ; Child ; Bile Ducts/*abnormalities/pathology/surgery

The purpose of this study was to investigate and discuss imaging methods and management strategies for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies. In this study we reviewed and analyzed 72 patients with congenital choledochal cyst, ranging in age from 15 days to 12 years old and who were seen at our hospital during the past 12 years, from January 1993 to October 2005. The image manifestation and clinical significance of patients with co- xisting intrahepatic biliary dilation and aberrant bile duct were carefully examined during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of the cystic type. That is, the orifice of the dilated intrahepatic tract that converged into the common hepatic duct showed membrane or septum-like stenosis. In 10 cases the dilation tapered off from the porta hepatis to the initiating terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left hepatic ducts converged at the choledochal cyst. In conclusion, the imaging methods for intrahepatic bile duct dilation possess important clinical significance. Further, for hepatojejunostomy with radical excision of a choledochal cyst, additional operative procedures for intrahepatic stenosis, possible bile duct malformation and pancreaticobiliary common duct calculi can potentially reduce postoperative complications.
Tomography, X-Ray Computed ; Postoperative Complications/ultrasonography ; Male ; Liver Diseases/complications/*radiography/surgery ; Infant, Newborn ; Infant ; Humans ; Female ; Choledochal Cyst/complications/*radiography/surgery ; Cholangiography ; Child, Preschool ; Child ; Bile Ducts/*abnormalities/pathology/surgery

Objective:To investigate the application value of Hisense computer-assisted surgery system (CAS) three-dimensional reconstruction in the precision treatment of pediatric liver tumors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 82 children with liver tumors who were admitted to Affiliated Hospital of Qingdao University from January 2013 to September 2021 were collected. There were 39 males and 43 females, aged 13(19)months. Children underwent upper abdominal dynamic enhanced computed tomography (CT) examination, and three-dimensional reconstruction was performed on CT images of arterial, equili-brium and venous phases with Hisense CAS. Surgical feasibility and scheme were evaluated and conducted based on the results of upper abdominal dynamic enhanced CT examination, and then revised according to three-dimensional reconstruction results of Hisense CAS. Observation indicators: (1) comparison of surgical scheme between two-dimensional enhanced CT images and three-dimensional reconstruction results of Hisense CAS; (2) intraoperative and postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination to detect postoperative compli-cations and residual liver compensation up to November 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were described as absolute numbers or percentages. Results:(1) Comparison of surgical scheme between two-dimensional CT images and three-dimensional reconstruction results of Hisense CAS. ① Based on the two-dimensional CT images, 42 cases of 82 children could undergo one-stage resection and 40 children could not. However, based on the three-dimensional reconstruction results of Hisense CAS, 48 cases of 82 children could undergo one-stage resection and 34 children could not. There were 6 children with one-stage resection feasibility based on the three-dimensional reconstruction results of Hisense CAS rather than the two-dimensional CT images. For the 34 children undergoing chemotherapy firstly, 31 cases had surgical feasibility after chemotherapy based on the two-dimensional CT images and 3 cases could not undergo surgery because of unapparent tumor regression or tumor surrounding impor-tant vessels. However, the 34 children had surgical feasibility after chemotherapy based on the three-dimensional reconstruction results of Hisense CAS. The revision rate of surgical feasibility was 11.0%(9/82) for the 82 children. ② Based on the two-dimensional CT images, 15 cases of 82 children underwent liver left lobectomy, 21 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 13 cases underwent extended left hemihepatectomy, 23 cases underwent extended right hemihepatectomy, 3 cases underwent segmental hepatectomy. However, based on the three-dimensional reconstruction results of Hisense CAS, 20 cases of 82 children underwent liver left lobectomy, 29 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 7 cases underwent extended left hemihepatectomy, 14 cases underwent extended right hemihepatectomy, 5 cases underwent segmental hepatectomy. The revision rate of surgical scheme was 36.6%(30/82) for the 82 children. (2) Intraoperative and postoperative situations. The operation time, volume of intraoperative blood loss, duration of postoperative hospital stay of the 82 children were (182±18)minutes, 20(10)mL, (10.2±1.9)days, respectively. (3) Follow-up. All the 82 children were followed up for 10 (range, 2?18)months. There was no obvious complication occurred to the 82 children after surgery, and the residual liver can satisfy the liver compensation of body. All the children survived well.Conclusion:Three-dimensional reconstruction of Hisense CAS is conducive to judging the surgical feasibility and formulation of accurate surgical plan of children with liver tumors.

Methods:Two thousand standard sections images werre collected from 2 000 clinical retrospective pediatric hip ultrasound videos from January 2019 to January 2021. All standard sections were annotated by the annotation team through the self-designed software based on Python 3.6 environment for image cross-media data annotation and manual review standardization process with unified standards. Among them, 1 753 were randomly selected for training the deep learning system, and the remaining 247 were used for testing the system. Further, 200 standard sections were randomly selected from the test set, and 8 clinicians independently completed the film reading annotation. The 8 independent results were then compared with the AI results.Results:The testing set consists of 247 patients. Compared with the clinician's measurements, the area under the receiver operating characteristic curve (AUC) of diagnosing hip joint maturity was 0.865, the sensitivity was 76.19%, and the specificity was 96.9%. The AUC of AI system interpretation under Graf detailed typing was 0.575, the sensitivity was 25.90%, the specificity was 89.10%. The 95% LoA of α-angle determined by Bland-Altman method, of -4.7051° to 6.5948° ( Bias -0.94, P<0.001), compared with clinicians' measurements. The 95% LoA of β-angle, of -7.7191 to 6.8777 ( Bias -0.42, P=0.077). Compared with those from 8 clinicians, the results of AI system interpretation were more stable, and the β-angle effect was more prominent. Conclusion:The AI system can quickly and accurately measure the Graf correlation index of standard DDH ultrasonic standard diagnosis plane.

OBJECTIVE： To design and optimize the formulation and technology of Theophylline hydrophilic gel matrix sustained-release tablets （self-made sustained-release tablets for short） based on the concept of “Quality by Design” （QbD）. METHODS： Diluent type， tablet diameter， the property of adhesive （ratio of different adhesive types）， the amount of adhesive were regarded as critical process parameters （CPPs）. Similarity factor of dissolution curves of self-made Theophylline sustained-release tablets and reference preparation and its accumulative release rate at different time points were regarded as critical quality attributes （CQAs）. L18（34） orthogonal tablet was adopted for design and trial， and secondary polynomial regression model was established. By using Modde 12.0 software， the design space and its acceptable range （PAR） were calculated through the optimal model. The optimal formulation and technology of Theophylline sustained-release tablets was determined， and validation test and Monte Carlo simulation verification were conducted. RESULTS： The optimal model with good coincidence， accuracy， validity and reproducibility was obtained， which could better fit the relationship between CQAs and CPPs. The design space and PAR value were obtained by further calculation （The optimum value of diluent was lactose； tablet diameter was 9.07-9.33 mm， and the optimal value was 9.20 mm； ratio of HPMC K4M to HPMC was 0.50-0.83， and the optimal value was 0.80； total amount of HPMC was 0.036 0-0.041 3 g per tablet， and the optimal value was 0.038 g per tablet）. The optimal formulation and technology included that ratio of theophylline， HPMC K4M and HPMC K100M were 50％， 15.48％ and 3.87％， respectively； the rest was filled with lactose and the diameter of the tablet was 9.20 mm. The results of validation confirmed that self-made Theophylline sustained-release tablets had similar in vitro release behavior compared with reference preparation. CONCLUSIONS： Based on the concept of QbD， the formulation and technology of Theophylline sustained-release tablets can meet the requirements of design， and the CPPs can be adjusted within the PAR range to meet the requirements of CQAs. This shows that the QbD concept is scientific and effective in the design and optimization of the formulation and technology of sustained and controlled release preparations.

Mycophenolic acid (MPA, ) and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases. Despite chemical synthetic achievements, the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of , especially the processes involving the cleavage of the prenyl side chain between DHMP () and DMMPA (), remains unknown. In this work, we identified a membrane-bound prenyltransferase, PgMpaA, that transfers FPP to to yield FDHMP (). Compound undergoes the first cleavage step a new globin-like enzyme PgMpaB to form a cryptic intermediate . Heterologous expression of genes in demonstrates that the second cleavage step (from to ) of is a cluster-independent process . Our results, especially the discovery of the broad tolerance of substrates recognized by PgMpaB, set up a strategy for the formation of "pseudo-isopentenyl" natural products using fungal globin-like enzymes.