Strategic management of tributary veins including concomitant versus staged intervention during endovenous thermal ablation for truncal varicose veins remains debated. Concomitant procedures mainly involves thermal ablation with ultrasound-guided foam sclerotherapy or phlebectomy. Staged strategies include initial truncal ablation followed by deliberated tributary management. Major venous disease guidelines exhibit substantial divergence,Japanese Society of Phlebology guidelines in 2019 contraindicate concomitant procedures, European Society for Vascular Surgery 2022 Clinical Practice Guidelines and Chinese frameworks endorse individualized decision-making,while American Vein and Lymphatic Society guidelines in 2023 prioritize concomitant procedures. Systematic literature review reveals that concomitant procedures do not uniformly translate into reduced reintervention rates or improved early Venous Clinical Severity Scores, yet consistently incur elevated complication risks and postoperative pain. Conversely, staged strategies offer superior tolerability with minimized complications. Hemodynamic principles indicate that most competent tributaries undergo partial or complete regression within 6 weeks to 6 months post-ablation and hemodynamic studies demonstrate that staged approaches preserve the drainage function of tributaries, preventing edema in their respective drainage territories and reducing tributary intervention rates. Future multicenter randomized controlled trials are imperative to delineate comparative outcomes between concomitant and staged management of truncal and tributary veins.

To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Strategic management of tributary veins including concomitant versus staged intervention during endovenous thermal ablation for truncal varicose veins remains debated. Concomitant procedures mainly involves thermal ablation with ultrasound-guided foam sclerotherapy or phlebectomy. Staged strategies include initial truncal ablation followed by deliberated tributary management. Major venous disease guidelines exhibit substantial divergence,Japanese Society of Phlebology guidelines in 2019 contraindicate concomitant procedures, European Society for Vascular Surgery 2022 Clinical Practice Guidelines and Chinese frameworks endorse individualized decision-making,while American Vein and Lymphatic Society guidelines in 2023 prioritize concomitant procedures. Systematic literature review reveals that concomitant procedures do not uniformly translate into reduced reintervention rates or improved early Venous Clinical Severity Scores, yet consistently incur elevated complication risks and postoperative pain. Conversely, staged strategies offer superior tolerability with minimized complications. Hemodynamic principles indicate that most competent tributaries undergo partial or complete regression within 6 weeks to 6 months post-ablation and hemodynamic studies demonstrate that staged approaches preserve the drainage function of tributaries, preventing edema in their respective drainage territories and reducing tributary intervention rates. Future multicenter randomized controlled trials are imperative to delineate comparative outcomes between concomitant and staged management of truncal and tributary veins.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

OBJECTIVE: To investigate the effects of methanol-ethyl acetate partitioned fractions from (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells. METHODS: The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of . The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts. RESULTS: MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner ( < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner ( < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax ( < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice. CONCLUSIONS The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both and , suggesting their value as promising therapeutic agents against lung cancer.
Acetates ; Animals ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Heterografts ; Humans ; Lung Neoplasms ; pathology ; Methanol ; Mice ; Mice, Nude ; Plant Extracts ; isolation & purification ; pharmacology

Objective To explore the pathological features of Aβ1-42 deposition and its correlation with Apolipoprotein E in brain of streptozotocin (STZ)-induced type Ⅱ diabetic rats.Methods High fat diet combined with small dose of STZ induced diabetic rats were adopted as experiment rats,and randomly divided into 3 months old diabetes mellitus group and 6 months old diabetes mellitus group (n=15).Healthy Wistar rats were adopted as control rats,and divided 3 months old control group and 6 months old control group (n=15).The Aβ1-42 and ApoE location and expressions were detected by immtmohistochemistry.Real-time fluorogenic quantitative-PCR and Westem blotting were used to detect the mRNA and protein levels of ApoE in each group.Results Immunohistochemical results showed that Aβ1-42 in the brain of the diabetic rats gathered around the vessel wall and blood vessel.The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group as compared with those in the 3 months old diabetes mellitus group (P＜0.05).The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old control groupas compared with those in the 3 months old control group (P＜0.05).As compared with that in the 6 months old control group,the number of Aβ11-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group (P＜0.05).As compared with that in the 3 months old control group,the number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions was significantly increased in the 3 months old diabetes mellitus group (P＜0.05).Person correlation coefficient indicated that the number of positively-stained cells of Aβ-42 was positively correlated to ApoE protein expression level (r=0.9755,P=0.000).Conclusions Aβ1-42 in the brain of type Ⅱ diabetic rats expresses both in blood vessel wall and around blood vessel.Age and duration of diabetes can increase the deposition of A3 and ApoE in brain tissues,and there is a positive correlation between them.