To investigate the effects of Wogonin (WO) on learning and memory impairment, Aβ1-42 was injected intracerebroventricularly to induced a mouse learning and memory impairment model, and D-galactose was injected intraperitoneally to induced a mouse acute aging model. Mice were administered WO (75, 150, or 300 mg/kg) by oral gavage for 28 consecutive days. Cognitive function was assessed using the Morris water maze (MWM), novel object recognition (NOR), and open field tests (OFT). In the Aβ1-42 model, WO treatment (150 and 300 mg/kg) significantly improved the recognition index in the NOR test, while the 150 mg/kg group showed increased target quadrant preference in the MWM test. No changes in the total distance traveled in OFT. In the D-galactose aging model, the 150 mg/kg WO group exhibited increased platform crossings in the MWM test, and all WO doses (75, 150, and 300 mg/kg) enhanced target quadrant preference, with no alterations in spontaneous movement. Western blot analysis revealed that WO significantly attenuated hippocampal apoptosis in both models. These findings suggest that WO ameliorates learning and memory impairment associated with Alzheimer’s disease and aging.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P＜0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P＜0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P＜0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of＜0.505×10-3 mm2/s and a postoperative D value of＜0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.

Objective To observe the value of clinical data combined with CT radiomics features for evaluating programmed cell death-ligand 1(PD-L1)status in gastric cancer.Methods Totally 277 gastric cancer patients were retrospectively enrolled and randomly divided into training set(n=195)and validation set(n=82)at the ratio of 7:3.There were 88 cases in PD-L1 positive subgroup and 107 cases in negative subgroup of training set,while 37 and 45 cases of validation set,respectively.The clinical and conventional CT features were compared between subgroups in both sets,the independent influencing factors of PD-L1 status in gastric cancer were analyzed,and radiomic features were screened based on CT data.Then clinical model,radiomics model and clinical-radiomics model were established,and the efficacy of each model for evaluating PD-L1 status in gastric cancer was observed.Results In training set,Borrmann type,cN stage,cM stage,clinical stage,maximum diameter and thickness were significant difference between subgroups(all P＜0.05).Borrmann type,clinical stage and the thickness were all independent influencing factors of PD-L1 positivity(all P＜0.05).The area under the curve(AUC)of clinical model,radiomic model and clinical-radiomics model for evaluating PD-L1 status in gastric cancer in training set was 0.748,0.832 and 0.841,respectively,and was 0.657,0.801 and 0.789 in validation set,respectively.AUC of clinical model was lower than the other models(all P＜0.05).Conclusion Clinical data combined with CT radiomics features was helpful for evaluating PD-L1 status in gastric cancer.

Intracranial aneurysm is a common cerebrovascular disease with high morbidity and mortality.Endovascular interventional therapy has advantages of high efficiency and minimally invasive.In this paper,the technical development of intracranial aneurysm interventional therapy Instruments was introduced,by interpreting the design mechanism of various types of coil,comparing the clinical benefits of braided and cut stents for assisting coil deployment,as well as analyzing the design principle and the optimization direction of currently the most eye-catching flow diverter,and thus the development and application of various interventional devices were discussed.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To evaluate the surgical treatments of refractory sclerosing peritonitis related peritoneal dialysis.Methods Clinical data of 15 patients with refractory sclerosing peritonitis related to peritoneal dialysis treated in the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from June 30,2014 to May 30,2018.Among them,5 cases underwent"open abdomen peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",4 cases underwent"laparoscopic peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",3 cases underwent"laparoscopic peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",2 cases underwent"open abdomen peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",and 1 case underwent"laparoscopic examination combined with laparotomy exploration and removal of lower abdominal catheter+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter".Age,gender,clinical symptoms,abdominal CT examination,peripheral blood routine,blood biochemistry,blood C-reactive protein(CRP),white blood cells,biochemistry,and aetiology of peritoneal dialysis fluid were collected and followed up,and the therapeutic effect was evaluated.Results 15 patients were transferred to the Department of Surgery after ineffective treatment in the Department of Internal Medicine.Preoperatively(after 5 days of antibiotic treatment)compared to before antibiotic treatment,there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Laparoscopic exploration or laparotomy exploration was performed,during which the peritoneal dialysis catheter was removed and the abdominal infection focus was cleared.A pelvic cavity washout drainage tube was left in place postoperatively.Fourteen patients had a good recovery after surgery,with effective control of peritonitis symptoms and no complications such as intestinal obstruction or enterocutaneous fistula.After the removal of the peritoneal dialysis catheter,all patients switched to hemodialysis.A comparison of inflammatory markers before and after surgery showed a significant decrease after surgery.Three days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Seven days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there was a significant decrease in blood WBC[(7.43±2.65)× 109/L VS(10.17±5.24)× 109/L],blood NEUT％[(88.23±9.02)％VS(85.07±11.57)％],and CRP[(152.88±113.01)mg/L VS(114.49±92.97)mg/L](P＜0.05);the peritoneal fluid WBC at 7 days postoperatively showed no significant change compared to before surgery(after 5 days of antibiotic treatment)(P＞0.05).The cases were followed up for at least 22 months,and 13 patients did not experience peritonitis or intestinal obstruction again.One patient died 39 days after surgery due to multiple organ failure,and one patient died from other causes after a 2-year follow-up.Conclusion For refractory sclerosing peritonitis related peritoneal dialysis that is ineffective in medical conservative treatment,On the basis of reasonable and effective antibiotics to control infection,surgical intervention should be actively carried out and surgical methods such as surgery should be used to control the progress of peritonitis,reduce mortality and improve the cure rate.

Objective:To explore the effects of applying peer-assisted learning (PAL) combined with modular teaching in physiology education, and to explore a more suitable mode for physiology teaching and learning.Methods:We selected a total of 89 undergraduate medical students of grade 2022 from a university offering physiology courses from February 28 to June 30, 2022. They were assigned using a random number table into experimental class (44 students) and control class (45 students). The experimental class adopted PAL with modular teaching, while the control class adopted the online and offline hybrid teaching method. The two classes were compared for teaching effects in terms of the completion rate of task points, final assessment scores, and questionnaire results. SPSS 19.0 was used to perform the independent samples t-test and the chi-square test. Results:The final exam scores for the objective questions of the experimental class and the control class were (43.04±3.25) and (40.24±8.64), respectively; the scores for the subjective items were (44.49±2.80) and (39.21±5.71), respectively; and the total scores were (87.53±4.24) and (79.40±12.08), respectively, all with significant differences between the two classes. There were significant differences in students' learning autonomy, micro-video preview rate, problem discussion participation rate, unit self-test participation rate, and after-class homework completion rate. The questionnaire survey showed that students in the experimental class believed that this teaching model was helpful for improving students' comprehensive qualities.Conclusions:PAL combined with modular teaching can effectively improve physiology teaching effects and students' learning autonomy and comprehensive abilities.

Objective To investigate the chemical composition from the flowers of Callerya speciosa,and reveal the metabolites difference at different flowering periods based on metabolomics technology.Methods The primary and secondary metabolites,volatile chemical components in flowers of C.speciosa were analyzed combined by GC-MS and UPLC-Q-Exactive MS.Principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and hierarchical cluster analysis(HCA)were performed to identify differential metabolites.Results A total of 332 compounds were identified by UPLC-Q-Exactive MS,mainly including secondary metabolites such as flavonoids,triterpenoids,phenylpropanoids.A total of 297 compounds were identified by GC-MS,mainly including primary metabolites and volatile chemical components,such as organic acids,amino acids,saccharides,heterocycles,alcohols.The PCA analysis demonstrated that the metabolites of the four flowering periods were divided into two groups:bud,initial bloom and blooming periods clustered into one group,while wilting period clustered into the other group,the main differences were filtered and identified as flavonoids and triterpenoids,organic acids,respectively.Compared to the upright type,the flowers of vine type contained more characteristic flavonoids as differential metabolites during the bud,initial bloom and blooming periods,and some flavonoids decrease gradually with the development of flowering.Conclusion The results indicated that the flowers of C.speciosa possessed abundant active flavonoid metabolites for further utilization,and the best harvest stage is initial bloom,the best harvest plant is vine type.This study provides a scientific basis for the scientific development and rational use of the flowers of C.speciosa.