OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

Objective:To discuss the effect of erythritol on glucose and lipid metabolism in the body,and to clarify the mechanism of erythritol affecting liver metabolism based on metabonomics.Methods:The male ICR mice were randomly divided into normal group,sucrose group(2％sucrose),low dose of erythritol(1％erythritol)group,medium dose of erythritol(2％erythritol)group,and high dose of erythritol(4％erythritol)group,with 10 mice in each group.The corresponding concentrations of sucrose and erythritol solutions were prepared and placed in water bottles,and the mice were allowed to drink and eat freely for 12 consecutive weeks;the body mass,food intakes,and water intakes of the mice in various groups were measured.Commercial kits were used to detect the serum triglyceride(TG),total cholesterol(TC),and blood glucose levels of the mice in various groups;the liver indexes of the mice were calculated.Ultra performance liquid chromatography-orbitrap exactive mass spectrometry(UPLC-OE-MS)non-targeted metabonomics was used to detect the liver metabolites of the mice normal group and high dose of erythritol group;bioinformatics analysis was used to screen the differential liver metabolites between the two groups with variable importance in projection(VIP)＞1 and adjusted P＜0.05;Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed to investigate the functional roles of the differential liver metabolites.Results:Compared with normal group,there were no significant differences in the body mass,food intake,liver index,and blood lipid levels of the mice in various groups(P＞0.05);compared with normal group,the blood glucose level of the mice in high dose of erythritol group was significantly increased(P＜0.01).The metabonomics analysis of the liver tissues of the mice in two groups identified 1 144 metabolites,mainly including lipids and lipid-like molecules(17.39％),organic acids and derivatives(10.87％),organic heterocyclic compounds(5.80％),and organic oxygen compounds(5.07％).Compared with normal group,there were 138 differential liver metabolites in the mice in high dose of erythritol group,among which 112 metabolites were up-regulated and 26 metabolites were down-regulated.The KEGG signal pathway enrichment analysis results showed that the differential metabolites were mainly enriched in metabolism,steroid hormone biosynthesis,cortisol synthesis and metabolism,and Cushing's syndrome pathways;the further topological analysis of the metabolic pathways results showed that the differential metabolites were mainly involved in sphingolipid metabolism,tricarboxylic acid cycle,riboflavin metabolism,steroid hormone biosynthesis,and purine metabolism signal pathways.Conclusion:Long-term intake of high dose of erythritol can increase the blood glucose level in the mice,and the mechanism may be that it affects the tricarboxylic acid cycle by interfering with riboflavin metabolism and interferes with sphingolipid metabolism,leading to impairment of the blood glucose control system.

Objective To evaluate the application of rabbit liver cancer model in teaching interventional medicine for graduate students.Methods A total of 10 first-year master graduate students majoring in Radiological Imaging(Interventional Medicine).who were studying at Zhengzhou University of China,were enrolled in this study.The rabbit liver cancer model was used as the experimental teaching materials.The teaching contents included the establishment of rabbit liver cancer model,the interventional operation of rabbit liver cancer,the method of scientific research and teaching,the evaluation of the teaching effect,and the survey of student satisfaction.Results Under the guidance of teaching tutor,the success rate of VX2 rabbit liver cancer modeling performed by the 10 master graduate students majoring in interventional medicine was 100％,and the mean operational quality assessment score was(11.5±2.0)points.During the operation of interventional surgery,the success rate of femoral artery puncture was also 100％,and the mean score for each interventional operation was(11.8±2.3)points.The students'experimental designs were evaluated by the expert group,the results were as follows:2 cases were rated as excellent,7 cases were rated as good,and one case was rated as moderate.The degree of students'satisfaction with experimental teaching method was high,the specific scores of each item are as follows:the understanding of the rabbit liver cancer model was(4.80±0.40)points,the command of interventional technology was(4.60±0.49)points,and the quality and practicability of teaching materials was(4.90±0.30)points.Conclusion This teaching method of using rabbit liver cancer model experiment can improve the animal experiment ability,interventional operation ability and scientific research innovation ability of graduate students.Animal model teaching method is an innovation of teaching mode for graduate students majoring in interventional medicine.

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4–120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4–120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4–120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Objective:To investigate clinicopathological characteristics and efficacy of conversion therapy in patients with metastatic gastric cancer.Methods:The clinicopathological and follow-up data of metastatic gastric cancer patients at the Department of Gastrointestinal Surgery of Peking University People's Hospital from Jan 2018 to Jun 2021 were retrospectively studied. Multivariate Logistic regression analysis was used to identify independent characteristics for pathological complete response (PCR). The influence of stage of metastatic gastric cancer and pathological response on prognosis were analyzed by Kaplan-Meier curve.Results:A total of 31 patients were enrolled, and 13 tumors located at the cardia or fundus, 8 at body, other 10 at pylorus or antrum . Baseline CT evaluation showed retroperitoneal lymph node metastasis in 10 cases, intraperitoneal metastasis in 10 cases, liver metastasis in 2 cases, adrenal and splenic metastasis in 1 case respectively, and multiple metastasis in 5 cases. After conversion therapy, 8 (26%) cases had pathological T0, 16 cases (52%) had pathological N0 and 7 cases (22%) had pathological complete response. Multivariate Logistic regression analysis showed retroperitoneal lymph node metastasis ( OR: 20.082, 95% CI: 2.141-188.315, P=0.009) was the only independent risk factor of PCR. Meanwhile, Kaplan-Meier curve showed pT0 improved disease-free survival significantly ( P=0.021). Conclusions:Metastatic gastric cancer patients with retroperitoneal lymph node metastasis alone had a tolerable conversion therapy effect. pT0 is a significant factor in improving prognosis.

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound