Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is a recognition protein for N⁶-methyladenosine (m⁶A), mediating the stability of downstream mRNA, and is a promising anti-tumor target. Based on the lead compound 1g from previous screening, this study designed and synthesized 52 IGF2BP2 small molecule inhibitors using thiazole hydrazone as the parent nucleus. Among them, 9g, 10g, 37g, 47g and 52g showed good inhibitory activities. This work represents an initial exploration in the development of small molecule inhibitors targeting IGF2BP2, using thiazolehydrazone as the core structure. It lays a foundation for subsequent related research.

Acute mitral regurgitation(MR)in the setting of myocardial infarction(MI)may be the result of papillary muscle rupture(PMR).The clinical presentation can be catastrophic,with refractory cardiogenic shock.This condition is associated with high morbidity and mortality.Transcatheter edge-to-edge repair(TEER)has become increasingly common in treating severe mitral regurgitation.This case details a successful TEER is feasible and safe in patients with acute MR following MI.TEER is an emerging treatment option in this clinical scenario that should be taken into consideration.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Aceria pallida is one of the most common pests in the main production areas of Lycium barbarum in China. The mite mainly feeds on foliage, leading to local tissue deformation and formation of massive galls, which seriously affects the growth and yield of L. barbarum. However, little is known about the influence of galling organisms on plant primary and secondary metabolism. In order to compare the metabolites differences between healthy and the mite infested leaves of wolfberry, and provide a scientific basis for the development and utilization of the galled leaves, L. barbarum seedlings were infested with A. pallida artificially in the laboratory, the metabolites of L. barbarum leaves were determined by LC-MS/MS. Our results showed that the leaves were rich in amino acids and flavonoid compounds. A total of 204 compounds from 16 classes were detected in L. barbarum leaves based on LC-MS/MS. The primary metabolites are mainly amino acids, and the secondary metabolites are mainly organic acids and flavonoids. The content of the metabolite in the leaves of L. barbarum was significantly affected by the mite, 30 metabolites such as flavonoids and phenylpropanoids were significantly changed, 21 metabolites were up-regulated and 9 metabolites were down-regulated significantly. There were 8 compounds which has pharmacological and biological activity, such as eriodictyol, isorhamnetin-3-O-neohesperidoside and scopoletin up-regulated significantly. Based on the above findings, we suggest that the galled leaves of L.barbarum have a potential to be developed in the future.
China ; Chromatography, Liquid ; Lycium ; Metabolomics ; Plant Leaves ; Tandem Mass Spectrometry

Objective To explore the application value of three-dimensional visual (3DV) assessment and virtual reality (VR) study of type Ⅲ and Ⅳ hilar cholangiocarcinoma with portal vein as the axis.Methods The CT image data of 10 patients who were diagnosed as Bismuth type Ⅲ and Ⅳ hilar cholangiocarcinoma by B-ultrasound and CT in Zhujiang Hospital,Southern Medical University were imported into 3D visualization system (3DVS) for 3D image reconstruction,and the portal vein was used as the axis for 3DV analysis and evaluation.The 3D data were then imported into the VR development engine to perform VR research,so as to help the operation planning.Both of the image data were taken into the operation room for intraoperative navigation.Results 10 patients completed 3D visualization reconstruction and VR model transformation.According to the 3D visualization of hepatic hilar hepatocarcinoma,there were 1 case of type Ⅱ,2 cases of type Ⅲa,5 cases of type Ⅲb,1 case of type Ⅳa and 1 case of type Ⅳb.The portal vein was classified according to Cheng type:6 cases of type Ⅰ,3 cases of type Ⅱ,and 1 case of type Ⅲ.The hepatic artery was classified according to Michels type:5 cases of type Ⅰ,1 case of type Ⅱ,3 cases of type Ⅲ,and 1 case of type Ⅸ.The 3DV assessment and VR study were almost consistent with the intraoperative findings.No liver failure or death occurred during the perioperative period.Conclusion The 3DV assessment and VR study with the portal vein as the axis have potential application for the surgical treatment of type Ⅲ and Ⅳ hilar cholangiocarcinoma.

Objective To explore the clinical application value of three-dimensional visualization of blood vessels as the axis and virtual reality technology in giant liver cancer.Methods Thin-layer CT image data of 13 patients who were diagnosed as giant primary liver cancer were collected for three-dimensional reconstruction,and then transformed into VR model.The anatomical relationship between the tumor and its surrounding important structures was analyzed.The preoperative evaluation,classification and surgical planning based on blood vessels as the axis were carried out to guide intraoperative navigation.The consistency was verified by the intraoperative rapid pathological examination.Results 13 patients successfully achieved 3D reconstruction and VR model transformation.According to the 3D visualization classification of blood vessels as the axis.There were three cases of type Ⅰ a grade 1,two cases of type Ⅰa grade 2;one case of type Ⅱ a grade 2;one case of type Ⅱ b grade 3;two cases of type Ⅱ c grade 3;four cases of type Ⅱ a grade 3.Conclusions Three-dimensional visualization and VR technology can provide comprehensive information on the anatomical structure of liver cancer lesions and blood vessels,which is of great value in the application of giant liver cancer surgery.

Objective: To explore a novel method for preoperative precision assessment of centrally located hepatocellular carcinoma(HCC) with blood vessel as axis based on three-dimensional(3D) visualization and virtual reality(VR) technology and its application values. Methods: High-quality thin-layer enhanced CT data were collected from 20 patients with centrally located HCC who treated at First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University from March 2017 to August 2018 diagnosed by preoperative examination. There were 18 males and 2 females, aged 28 to 69 years, all of Child-Pugh grade A. First of all, 3D reconstruction was performed by a 3D visualization software; then, the reconstructed 3D image was imported into VR development engine for VR research; afterwards, the analysis and evaluation system with blood vessel as axis was established based on 3D visualization classification of centrally located HCC; therefore, the relationship of the tumor to its major peripheral blood vessels was accurately judged and the surgical planning was formulated. Two images were brought into the operating room for navigation in surgery. The assessments results of preoperative data (CT and (or) MRI) and three-dimensional visualization of blood vessels in VR environment were compared; the values of the preoperative and postoperative hemoglobin, serum albumin and bilirubin were recorded and compared. Chi-square test, t-test and non-parametric test were used for the analysis of counting data, continuous measurement data and non-normal distribution measurement data, respectively. Results: 3D visualization modeling was completed in all of the 20 patients with centrally located HCC. According to the results of 3D visualization classification of centrally located HCC, there were 3 cases of type Ⅰ,1 case of type Ⅱ,4 cases of type Ⅲ,7 cases of type Ⅳ and 5 cases of type Ⅴ; according to the assessment and classification based on blood vessel as the axis, there were 6 cases of type Ⅰa,2 cases of type Ⅰb,2 cases of type Ⅱa,9 cases of type Ⅱb and 1 case of type Ⅱc. All patients underwent successful resection of tumor under the guidance of 3D visualization and VR technology. There were 15 cases whose assessment results based on preoperative CT/MRI were consistent with intraoperative findings, with a coincidence rate of 75.0%(15/20); while in VR environment, the assessment results of 3D visualization with blood vessel as axis were all consistent with the intraoperative findings, with coincidence rate of 100%(20/20). There was a statistically significant difference between the groups (χ²=5.714, P=0.017). There was no red blood cell transfusion in all patients during the operation. The preoperative hemoglobin was (128.8±14.9)g/L, and it was (119.8±12.5)g/L on postoperative day 1. There was no significant difference between these two sets of data (t=2.07, P=0.054). No death during the perioperative period and no complications such as hepatic failure, hemorrhage and biliary fistula after operation occurred. Conclusion Preoperative evaluation based on 3D visualization and VR technology with blood vessel as the axis has significant clinical value for preoperative planning and surgical navigation of centrally located HCC.

To identify the wolfberry gall mite species and their overwintering situation in different wolfberry production areas and to provide a scientific basis for their prevention and control. We investigate the phoresy overwintering situation of gall mite, and identify the species of gall mite. Our results showed that the phoretic gall mite was Aceria pallida in all the production areas. The phoresy of gall mite was a common occurrence in different production areas, and the phoresy probability was above 75%. The phoretic behavior of wolfberry gall mite occurred commonly in the other production areas. The control of this mite in different production areas should pay attention to their phoretic behavior.
Animals ; Lycium ; parasitology ; Mites ; classification ; growth & development ; Seasons

To compare the polysaccharides( LBLP),total flavonoids( LBLTF) and total phenols( LBLTP) of Lycium barbarum leaves from 14 production areas from Ningxia,Qinghai and Gansu at different harvesting time. Our results showed that there were significant difference of LBLP,LBLTF and LBLTP among different production areas. The LBLP collected from Xiangride township production area,Dulan,Qinghai was as high as 15. 02%. The LBLTF collected from Dagele township production area,Geermu,Qinghai was as high as28. 63%. The LBLTP collected from Keluke township production area,Delingha,Qinghai was as high as 16. 7%. There were also significant difference of these 3 components between different harvest periods. The average LBLP in May( 10. 20%) was significantly higher than that in June( 8. 49%). However,the average LBLTF( 17. 71%) and LBLTP( 12. 77%) in June was significantly higher than that in May( 14. 15%,11. 19%). The LBLTF and LBLTP have a positive correlation with the altitude of production areas,but there was no significant association between LBLP and altitude. The LBLP,LBLTF and LBLTP in different production areas and harvesting time was significant difference,the results provide some references for furthermore development and utilization of L. barbarum leaves.
Analysis of Variance ; China ; Flavonoids ; analysis ; Geography ; Lycium ; chemistry ; Phenols ; analysis ; Plant Leaves ; chemistry ; Polysaccharides ; analysis ; Seasons

BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. RESULTS: Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. CONCLUSION The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.
Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Chromosomal Proteins, Non-Histone ; antagonists & inhibitors ; Electrophoresis, Polyacrylamide Gel ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Liver Neoplasms ; drug therapy ; surgery ; Liver Regeneration ; physiology ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Sarcosine ; analogs & derivatives ; therapeutic use ; Xenograft Model Antitumor Assays