This study aimed to investigate the inhibitory effect of tubuloside B (Tub B) on amyloid β-protein (Aβ), and analyse the potential mechanism. A model of amyloid fibril was established by incubation of Aβ_1-42 in vitro. Thioflavin-T (ThT), Congo red (CR), 8-anilino-1-naphthene sulfonic acid (ANS) staining and transmission electron microscopy (TEM) were applied to detect the suppression of Tub B on the formation of Aβ_1-42 fibril. Circular dichroism (CD) was used to analyse the regulatory effect of Tub B on the secondary structure of Aβ_1-42. 3-(4,5-Dimethyl-2-thiazole) -2,5-diphenyltetrazolium bromide (MTT) and red blood cell hemolysis experiments were used to investigate the attenuation of Tub B on Aβ_1-42 induced cytotoxicity. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) staining was used to assess the expression of intracellular reactive oxygen species (ROS) induced by Aβ_1-42. And molecular docking experiment was used to explore the interaction between Tub B and Aβ_1-42. The results indicated that Tub B could inhibit Aβ_1-42 fibrillization in a certain extent, which retarded the structural transition of α-helix to β-sheet of Aβ_1-42, hampered the exposure of hydrophobic regions, and attenuated amyloid-induced cytotoxicity and hemolysis. In summary, Tub B can prevent the formation of Aβ_1-42 amyloid fibril, which may be related to its antioxidant activity and hydrogen bonding and hydrophobic interactions with protein molecules. All animal experiments were approved by the Experimental Animal Research Center of Air Force Medical University (No. 20190051).

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

Objective:To investigate the diagnostic value and imaging characteristics of MRI combined with 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT in focal cortical dysplasia (FCD) complicated with refractory epilepsy. Methods:A retrospective analysis was performed on 42 patients with FCD complicated with refractory epilepsy who were admitted to the Affiliated Hospital of Jining Medical University from January 2017 to December 2022. All patients underwent preoperative MRI and 18F-FDG PET/CT, and PET/MRI fusion was performed on the images. Chi-square test and Kappa consistency test were used to compare the localization diagnostic efficacy of PET/CT, MRI and PET/MRI fusion for epileptic foci. The patients were categorized based on gender, lesion location, pathological type, seizure type, and efficacy. Independent sample t-test and analysis of variance were used to compare maximum standardized uptake (SUVmax) values and asymmetry index (AI) of the patients between different groups. Results:Among the 42 patients, the positive rates of MRI, PET/CT, PET/MRI fusion examinations were 85.7%(36/42), 95.2%(40/42), 100.0%(42/42), the lateral localization rates were 71.4%(30/42), 92.9%(39/42), 95.2%(40/42), and the localization rates were 57.1%(24/42), 81.0%(34/42), 88.1%(37/42), respectively. There were significant differences in the lateral localization rates and localization rates of epileptogenic foci between MRI and PET/CT (χ 2=6.574, P=0.010; χ 2=5.570, P=0.018). There were significant differences in the positive rates of lesions, the lateral localization rates and the localization rates of epileptogenic foci between MRI and PET/MRI fusion (χ 2=6.385, P=0.012; χ 2=8.571, P=0.003; χ 2=10.118, P=0.001). There were no significant differences in the positive rates of lesions between MRI and PET/CT, and in the positive rates of lesions, the lateral localization rates and localization rates of epileptogenic foci between PET/CT and PET/MRI fusion (χ 2=2.184, P=0.139; χ 2=2.024, P=0.155; χ 2=0.210, P=0.647; χ 2=0.819, P=0.365). The Kappa consistency test of PET/CT and PET/MRI fusion imaging was performed for the location of epileptogenic foci, and the Kappa=0.721 was obtained, indicating that they were consistent in the location of epileptogenic foci. The SUVmax values of patients with temporal lobe epilepsy were lower, and the AI values were higher than that of patients with extra temporal lobe epilepsy (7.4±1.3 vs 9.6±1.6, 15.5±2.6 vs 12.9±2.4; t=5.154, 6.083; P=0.001, 0.001). The SUVmax values of patients with good efficacy (according to the Engel efficacy grading system, grades Ⅰ-Ⅱ indicating good efficacy) were higher, and the AI values were lower than that of patients with poor efficacy (according to the Engel efficacy grading system, grades Ⅲ-Ⅳ indicating poor efficacy; 9.5±1.9 vs 7.9±2.1, 13.5±3.3 vs 14.8±3.0; t=2.789, 3.722; P=0.042, 0.029). There were no significant differences in SUVmax and AI values among different genders, pathological types and seizure types (all P>0.05). Conclusions:The imaging characteristics of patients with different types of FCD complicated with refractory epilepsy are different. PET/MRI fusion is better than MRI in the diagnosis of FCD complicated with refractory epilepsy, and is consistent with PET/CT in the location of epileptogenic foci.

Objective To analyze the therapeutic effects and survival benefits of sintilimab combined with albumin-bound paclitaxel chemotherapy in the treatment of patients with advanced gastric cancer.Methods Patients with advanced gastric cancer were divided into the treatment group and the control group by cohort method.The control group was treated with albumin-bound paclitaxel-based chemotherapy[intravenous infusion of albumin-bound paclitaxel at 125 mg·m-2 from day 1 to day 8,for a cycle(21 days as a cycle);Tiggio capsule 40 mg·m-2·d-1 was taken orally for 1-14 days for 1 consecutive cycle;Trastuzumab was administered once every 3 weeks at an initial loading dose of 8 mg·kg-1,followed by maintenance treatment at a dose of 6 mg·kg-1 every 3 weeks].On this basis,the treatment group was treated with intravenous infusion of sintilimab injection at a dose of 200 mg·time-1 on the first day of each cycle,with 21 d as a cycle.After 6 cycles of continuous treatment,both groups were given maintenance treatment and were followed up for 8 months.The two groups were compared in terms of clinical efficacy,the levels of serum tumor markers[carbohydrate antigen 242(CA242),carbohydrate antigen 724(CA724),carcinoembryonic antigen(CEA),tissue polypeptide-specific antigen(TPS),soluble intercellular cell adhesion molecule-1(sICAM-1)and E-cadherin],survival and evaluated the safety.Results In this study,39 and 41 patients were enrolled in the control group and the treatment group,respectively.At the end of treatment,the objective response rates(ORR)in the treatment group and the control group were 56.10％and 33.33％;the disease control rates(DCR)were 78.05％and 48.71％.The differences were statistically significant(all P＜0.05).After treatment,serum CA242 levels in the treatment group and the control group were(57.64±5.82)and(68.95±7.23)mg·L-1;CA724 levels were(36.58±3.79)and(43.65±4.48)U·mL-1;CEA levels were(17.33±1.78)and(20.16±2.35)ng·mL-1;TPS levels were(21.35±2.44)and(37.65±3.84)U·L-1;sICAM-1 levels were(216.77±22.53)and(275.34±28.63)ng·mL-1;E-cadherin levels were(12.15±1.36)and(9.87±1.45)ng·mL-1.The differences were statistically significant(all P＜0.05).The average progression free survival(PFS)of the treatment group and the control group was 7.55 months and 7.17 months;PFS rates were 65.78％and 56.42％.The differences were statistically significant(P＜0.05).The adverse drug reactions in the treatment group and the control group were mainly bone marrow suppression,nausea and vomiting,liver function damage,peripheral nerve paresthesia,and hypothyroidism.There was no statistically significant difference in the above adverse drug reactions between the treatment group and the control group(all P＞0.05).Conclusion Sintilimab combined with albumin-bound paclitaxel chemotherapy is effective in the treatment of patients with advanced gastric cancer,which can significantly improve serum tumor markers and prolong PFS,with good safety.

Misuse of pyrrolizidine alkaloid (PA)-containing herbs is the major cause of hepatic sinusoidal obstruction syndrome (HSOS) in China. And diuretics are among the most commonly used medications for the treatment of PA-induced HSOS in clinical practice. As a traditional diuretic in traditional Chinese medicine, the diuretic mechanism of Alismatis Rhizoma (AR) has not been fully clarified, and there is no report on AR ameliorating PA-induced HSOS from a diuretic point of view. Therefore, this study aims to investigate the therapeutic potential of alisol B 23-acetate (AB23A) against acute liver injury induced by senecionine (a representative toxic PA) in mice, and to further elucidate its effect on impaired water-liquid balance in mice exposed to PA. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (Registration number: PZSHUTCM220808017). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Model of mice was induced by a single oral exposure of senecioine (50 mg·kg^-1) (SEN group), and AB23A (40 mg·kg^-1) intervention group (AB23A+SEN group), solvent control group (Ctrl group) and AB23A control group (AB23A group) were set up. The results showed that AB23A could significantly attenuate the levels of serum biochemical indices of liver functions in senecioine-induced acute liver injury mice, as evident by alleviated hepatocyte necrosis and hepatic sinusoidal stasis. AB23A also improved kidney function of mice exposed to senecionine, fascinated urinary excretion and repaired electrolyte disorders, as well as decreased content of senecioine metabolites. Further, the protein and mRNA expression of genes related to the water balance pathway were measured. AB23A could significantly down-regulate the elevated protein and mRNA expression levels of aquaporin 2 (AQP2) and angiotensin II type 1 receptor, and inhibit the transport of AQP2 to the apical plasma membrane induced by senecionine exposure. AB23A also significantly decreased serum levels of angiotensin II. In vitro studies further confirmed that AB23A regulates AQP2 expression in renal inner medullary collecting duct cells 3 (IMCD3). These data indicate that AB23A regulates the expression of AQP2 in renal medulla, thereby affecting its water reabsorption in mice with senecionine-induced acute liver injury. This work achieves a better understanding of the diuretic effect of AR, and provides experimental foundation and theoretical basis for the treatment of PA-induced acute liver injury by AR in clinics.

Objective To establish a new animal model of filum terminale traction tethered cord syndrome to explore its pathogenesis.Methods Sixteen New Zealand white rabbits were randomly divided into the traction group and the sham group,with 8 rabbits in each group.The traction group used silk thread to establish a model of filum terminale traction tethered cord syndrome,while the sham group only cut the filum terminale without traction.After 8 weeks,the behavioral Talov score,lumbosacral MRI examination,somatosensory evoked potential detection,urodynamic index test and pathological analysis were completed.Results At the 8th week after surgery,the hindlimb injury was obvious in the traction group,and the Talov scores at the 4th and 8th weeks after operation were lower than those in the sham group(P<0.001).The lumbosacral MRI results at 8 weeks after surgery showed that the distal filum terminale was pulled by silk thread,with bladder abnormal enlargement in sagital MRI in the traction group,while axial MRI showed the spinal cord within the spinal canal was subjected to mechanical forces in the downward and dorsal directions;the sagittal and axial MRI of the sham group showed that the spinal cord was located in the middle of the spinal canal and the bladder size was normal.At the 8th week after surgery,the amplitude in the traction group was significantly lower than that in the sham group(P<0.001),and the amplitude decreased by more than 50% .The overall latency period in the traction group was slightly longer than that in the sham group(P<0.05).The results of urodynamic examination showed that the maximum bladder capacity in the traction group was significantly higher than that in the sham group(Z=-3.361,P<0.001),the bladder pressure was significantly lower than that in the sham group(Z=-3.361,P<0.001),and the bladder compliance was significantly higher than that in the sham group(P<0.001).Pathological staining showed that the traction of the filum terminale on the spinal cord led to nerve tissue damage and degeneration of bladder epithelial cells.Conclusion This study successfully established a model of filum terminale traction tethered cord syndrome of New Zealand white rabbits,which can provide reference for exploring the pathogenesis of tethered cord and understanding the pathological process of spinal cord injury.

Objective:To investigate the effects of the "TECK" (theoretical class, experimental course, case discussion, and knowledge reinforcement) teaching model oriented by post competency in clinical pathology internship teaching.Methods:The intern students from 2015 to 2019 in the pathology direction of clinical medicine in the School of Pathology, Qiqihar Medical College, who were enrolled in the internship from 2019 to 2023, were selected as the research objects.We enrolled 32 medical students from grades 2017, 2018, and 2019 (research group) and 24 medical students from grades 2015 and 2016 (control group) who would participate in pathology internships. The control group adopted the traditional internship mode, while the research group adopted the competency-oriented "TECK" teaching mode. After the internship, the two groups were compared for internship assessment score and surveyed for post competency. With the use of SPSS 18.0 statistical software. Continuous data were presented as (mean±standard deviation) and t-test was used for comparison between groups. Count data were expressed in the number of cases, and chi-square test was used for comparison between groups.The significance level α was 0.05. Results:The research group showed significantly higher scores of skill assessment (82.81±4.20 vs. 79.58±5.09) and pathological diagnosis assessment (80.28±4.23 vs. 76.21±4.58) than the control group (both P<0.05), with no significant difference in the score of theoretical knowledge ( P>0.05). In terms of post competency, the research group was superior to the control group in clinical skills and medical care ability (12.38±0.94 vs. 11.35±0.76), disease prevention and health promotion ability (6.28±0.92 vs. 4.48±0.93), interpersonal communication and information management ability (19.81±1.09 vs. 17.00±1.28), and teamwork and scientific research ability (11.44±1.27 vs. 9.25±0.87; all P<0.05). There were no significant differences between the two groups in core values and professional literacy and medical knowledge and lifelong learning (both P>0.05). Conclusions:In undergraduate internships, the competency-oriented "TECK"teaching mode can significantly improve students' clinical operation and pathological diagnosis ability, and effectively cultivate their abilities of clinical skills and medical care, disease prevention and health promotion, interpersonal communication and information management, teamwork and scientific research.