Atlas of mildly and highly insoluble matrisome driving liver fibrosis.

The excessive deposition and cross-linking of core matrisome components typically result in abnormal remodeling of the extracellular matrix (ECM), leading to increased liver stiffness and worsening liver fibrosis. Exploring the biochemical properties of the ECM scaffold can deepen our understanding of the pathological mechanisms driving liver fibrosis and potentially facilitate the identification of therapeutic targets. While traditional sodium dodecyl sulfate (SDS)-based liver decellularization followed by proteomics can uncover the matrisome components within the ECM scaffold, it lacks the ability to reveal physicochemical characteristics like solubility. In our present study, using adult mouse liver as an example, we introduced a novel two-step workflow that combines our previously enhanced SDS (ESDS) decellularization with the conventional SDS method, enabling the identification of matrisome members with mild and/or high solubilities. Through this approach, we visualized the atlas of the mildly and highly insoluble matrisome contents in the adult mouse liver, as well as the regulatory network of highly insoluble matrisome that largely governs liver stiffness. Given the strong correlation between increased matrisome insolubility and heightened ECM stiffness, we believe that this methodology holds promise for future research focused on liver stiffness.

Effect of robotic versus laparoscopic surgery on postoperative wound infection in patients with cervical cancer: A meta-analysis.

The objective of this research is to evaluate the risk of postoperative infection and other risks associated with robotic radical hysterectomy (RRH) compared with laparoscopic radical hysterectomy (LRH). Recent studies on RRH versus LRH have not been conclusive for cervical carcinoma. Our group attempted to use meta-analyses to evaluate the effects of both RRH and LRH on postoperative outcomes in order to make sure that the best operative method was used to prevent wound infections. We looked up Cochrane Library and published databases for this research and found 594 findings. Articles were screened by title and abstract and then carefully examined for inclusion and exclusion criteria. Data extraction was performed independently by two researchers. Comparison studies were used to describe the incidence of wound complications after surgery. The publication bias was assessed using Egger regression correlation analysis. There were six trials eligible for inclusion, of which 491 RRH and 807 LRH. Depending on surgery for cervical carcinoma, it is true that there is a difference in the way that surgery affects the postoperative complications. Our analysis demonstrated that the use of robotic operation can decrease the amount of blood loss during operation as compared with routine laparoscopy (MD, -77.69; 95% CI, -132.08, -23.30; p = 0.005). However, there were no statistical differences in the incidence of postoperative wound infections (OR, 0.54; 95% CI, 0.25, 1.19; p = 0.13) and intraoperative operative time (MD, 13.01; 95% CI, -41.38, 67.41; p = 0.64) among the two procedures. There was no statistically significant difference between these two groups of patients with severe postoperative complications. Unlike other research, the findings of this meta-analysis are not consistent with the findings of the present study, which suggest that robotic operations cannot lower the rate of postoperative wound infections. However, because of the limitations and the retrospective character of the trials covered, these findings should be interpreted with care and more extensive research is required.

Structural and functional changes of the cerebellum in temporal lobe epilepsy.

Aims: This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information. Methods: The SUIT toolbox was utilized to perform cerebellar volume and diffusion analysis. In addition, we extracted the average diffusion values of cerebellar peduncle tracts to investigate microstructure alterations. Seed-based whole-brain analysis was used to investigate cerebellar-cerebral functional connectivity (FC). Subgroup analyses were performed to identify the cerebellar participation in TLE with/without hippocampal sclerosis (HS)/focal-to-bilateral tonic-clonic seizure (FBTCS) and TLE with different lateralization. Results: TLE showed widespread gray matter atrophy in bilateral crusII, VIIb, VIIIb, left crusI, and left VIIIa. Both voxel and tract analysis observed diffusion abnormalities in cerebellar afferent peduncles. Reduced FC between the right crus II and the left parahippocampal cortex was found in TLE. Additionally, TLE showed increased FCs between left lobules VI-VIII and cortical nodes of the dorsal attention and visual networks. Across all patients, decreased FC was associated with poorer cognitive function, while increased FCs appeared to reflect compensatory effects. The cerebellar structural changes were mainly observed in HS and FBTCS subgroups and were regardless of seizure lateralization, while cerebellar-cerebral FC alterations were similar in all subgroups. Conclusion: TLE exhibited microstructural changes in the cerebellum, mainly related to HS and FBTCS. In addition, altered cerebellar-cerebral functional connectivity is associated with common cognitive alterations in TLE.

Balloon-compression endoscopic injection sclerotherapy versus transjugular intrahepatic portosystemic shunt for esophageal variceal rebleeding.

BACKGROUND: In cirrhotic patients, recurrent bleeding after the first episode of esophageal variceal bleeding (EVB) is common and lethal. The present study was aimed to compare balloon-compression endoscopic injection sclerotherapy (bc-EIS) with transjugular intrahepatic portosystemic shunt (TIPS) for the prophylaxis of variceal rebleeding. METHODS: Between June 2020 and September 2022, 81 cirrhotic patients with EVB (42 in the bc-EIS group and 39 in the TIPS group) were evaluated retrospectively. The occurrence of rebleeding, hepatic encephalopathy (HE) or other complications, as well as liver functions and survival rate were compared between two groups. RESULTS: During the 12 months of follow-up, variceal eradication was achieved in 40 (95.24%) patients of the bc-EIS group after a mean of 1.80 ± 0.94 sessions. TIPS was successfully performed in 39 (100%) patients. No significant difference in the variceal rebleeding rate was observed between bc-EIS and TIPS groups (16.67 vs. 17.95%; p = 0.111). While the bc-EIS group showed significantly decreased incidence of HE (2.38 vs. 17.95%; p < 0.001) and lower level of total bilirubin (p < 0.05) in comparison with the TIPS group. The difference in mortality between the two groups failed to reach statistical significance (0.00 vs. 7.69%; p = 0.107). CONCLUSION: Bc-EIS is not inferior to TIPS in the survival and control of variceal rebleeding, but associated with decreased risk of HE and liver dysfunction.

Transcriptome analysis of Lr19-virulent mutants provides clues for the AvrLr19 of Puccinia triticina.

Introduction: Wheat leaf rust caused by Puccinia triticina (Pt) remains one of the most destructive diseases of common wheat worldwide. Understanding the pathogenicity mechanisms of Pt is important to control wheat leaf rust. Methods: The urediniospores of Pt race PHNT (wheat leaf rust resistance gene Lr19-avirulent isolate) were mutagenized with ethyl methanesulfonate (EMS), and two Lr19-virulent mutants named M1 and M2 were isolated. RNA sequencing was performed on samples collected from wheat cultivars Chinese Spring and TcLr19 infected with wild-type (WT) PHNT, M1, and M2 isolates at 14 days post-inoculation (dpi), respectively. Screening AvrLr19 candidates by quantitative reverse transcription PCR (qPCR) and Agrobacterium-mediated transient assays in Nicotiana benthamiana. Results: 560 genes with single nucleotide polymorphisms (SNPs) and insertions or deletions (Indels) from non-differentially expressed genes were identified. Among them, 10 secreted proteins were screened based on their fragments per kilobase of exon model per million mapped reads (FPKM) values in the database. qPCR results showed that the expression profiles of 7 secreted proteins including PTTG_27471, PTTG_12441, PTTG_28324, PTTG_26499, PTTG_06910, PTTG_26516, and PTTG_03570 among 10 secreted proteins in mutants were significantly different with that in wild-type isolate after infection wheat TcLr19 and might be related to the recognition between Lr19 and AvrLr19. In addition, a total of 216 differentially expressed genes (DEGs) were obtained from three different sample comparisons including M1-vs-WT, M2-vs-WT, and M1-vs-M2. Among 216 DEGs, 15 were predicted to be secreted proteins. One secreted protein named PTTG_04779 could inhibit programmed progress of cell death (PCD) induced by apoptosis-controlling genes B-cell lymphoma-2 associated X protein (BAX) on Nicotiana benthamiana, indicating that it might play a virulence function in plant. Taken together, total 8 secreted proteins, PTTG_04779, PTTG_27471, PTTG_12441, PTTG_28324, PTTG_26499, PTTG_06910, PTTG_26516, PTTG_03570 are identified as AvrLr19 candidates. Discussion: Our results showed that a large number of genes participate in the interaction between Pt and TcLr19, which will provide valuable resources for the identification of AvrLr19 candidates and pathogenesis-related genes.

Identification of mRNA expression biomarkers associated with epilepsy and response to valproate with co-expression analysis.

Purpose: Valproate (VPA) resistance was reported to be an important predictor of intractable epilepsy. We conducted this study to identify candidate biomarkers in peripheral blood correlated with VPA resistance. Methods: The microarray dataset (GSE143272) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to construct co-expression modules and obtain the most prominent module associated with VPA resistance. Differentially expressed genes (DEGs) between VPA-responsive and VPA-resistant patients were obtained using the "Limma" package in R. The intersections between the most prominent module and DEGs were identified as target genes. Metascape was performed to discover the possible involved pathways of the target genes. GeneCards database was used to know the function of each target gene. Results: All genes in the GSE143272 were divided into 24 different modules. Among these modules, the darkred module showed a pivotal correlation with VPA resistance. A total of 70 DEGs between VPA-responsive and VPA-resistant patients were identified. After taking the intersection, 25 target genes were obtained. The 25 target genes were significantly enriched in T cell receptor recognition, T cell receptor signaling pathway, regulation of T cell activation, cytokine-cytokine receptor interaction, and in utero embryonic development. Half of the target genes (CD3D, CD3G, CXCR3, CXCR6, GATA3, GZMK, IL7R, LIME1, SIRPG, THEMIS, TRAT1, and ZNF683) were directly involved in the T cell development, migration, and activation signaling pathway. Conclusion: We identified 25 target genes prominently associated with VPA resistance, which could be potential candidate biomarkers for epilepsy resistance in peripheral blood. The peripheral blood T cells may play a crucial role in VPA resistance. Those genes and pathways might become therapeutic targets with clinical usefulness in the future.

Efficient Initial Eradication of Large Esophageal Varices by Balloon-compression Endoscopic Injection Sclerotherapy.

BACKGROUND: The management of large esophageal varices (EVs) remains challenging because of the difficulty of endoscopic variceal ligation and fatal post-endoscopic variceal ligation bleeding ulcers. The current study evaluated the efficacy and safety of balloon-compression endoscopic injection sclerotherapy (bc-EIS) in the treatment of large EVs. MATERIALS AND METHODS: This retrospective study included 105 patients with cirrhosis exhibiting large EVs (64 in the bc-EIS group and 41 in the EIS group). Primary outcomes included the initial rate of variceal eradication and intraoperative bleeding signs. Secondary outcomes included incidences of rebleeding, mortality, complications, and optimal time of balloon-compression (bc). RESULTS: The initial rate of variceal eradication in the bc-EIS group was significantly higher than that in the EIS group (46.9 vs. 24.4%; P =0.021). The incidence of intraoperative bleeding, which was represented as oozing and spurting, in the bc-EIS group was markedly lower than that in the EIS group (43.8 vs. 61.0% and 9.4 vs. 39.0%, respectively; P =0.043). Patients in the bc-EIS group showed a significantly lower incidence of rebleeding (0.0 vs. 17.1%; P =0.001). However, no significant difference in mortality rate was observed between different groups. Chest pain or discomfort tended to be more common in the EIS group than in the bc-EIS group (58.5 vs. 17.2%; P =0.001). The cut-off value of 11.5-minutes appeared to have a maximum combined sensitivity and specificity of 80.0% and 58.8%, respectively. The area under the curve was 0.708 (95% confidence interval =0.576-0.839; P =0.004). CONCLUSION: bc-EIS could achieve a higher variceal eradication rate and milder intraoperative bleeding signs in large EVs. Furthermore, 11.5-minutes appeared to be the optimal compression time in bc-EIS.

Comparison of transjugular intrahepatic portosystemic with endoscopic treatment plus anticoagulation for esophageal variceal bleeding and portal vein thrombosis in liver cirrhosis.

BACKGROUND AND AIM: The optimal management of esophageal variceal bleeding (EVB) and portal vein thrombosis (PVT) in liver cirrhosis has not been well-established. The aim of the present study was to compare the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic treatment (ET) plus anticoagulation in cirrhotic patients with EVB and PVT. PATIENTS AND METHODS: A total of 66 cirrhotic patients with PVT and EVB (31 in the TIPS group and 35 in the ET plus anticoagulation group) were evaluated retrospectively between January 2016 and January 2022. RESULTS: During the follow-up period, 85.5% of patients in the TIPS group achieved complete recanalization of the portal vein, as compared with 19.6% in the ET plus anticoagulation group (p < .001). The cumulative 5-year rate of variceal rebleeding in the TIPS group was significantly lower than that in the ET plus anticoagulation group (31.0 vs. 50.1%; p = .017). The TIPS group exhibited a significantly higher incidence of overt hepatic encephalopathy (HE) than the ET plus anticoagulation group (25.8 vs. 5.7%; p = .037). No difference in the 5-year survival rate (74.1 vs. 85.7%; p = .692) and probability of other complications was observed between the two groups. CONCLUSION: TIPS was superior to ET plus anticoagulation in preventing variceal rebleeding and achieving recanalization of PVT but increased the incidence of overt HE without improving the survival rate.

Novel balloon compression-assisted endoscopic injection sclerotherapy and endoscopic variceal ligation in the treatment of esophageal varices: a prospective randomized study.

BACKGROUND: Herein, our group designed a novel technology, termed balloon compression-assisted endoscopic injection sclerotherapy (bc-EIS), which was applied to improve the efficiency of eradicating esophageal varices (EVs). The present study aimed to compare the rate of eradication and efficacy between bc-EIS and endoscopic variceal ligation (EVL) in the management of EVs. METHODS: Ninety-five patients with esophageal variceal bleeding (EVB) were randomly assigned to receive bc-EIS or ligation alone. Additional treatment sessions were held 1 month later and then at 3-month intervals until eradication of the varices was achieved. Endoscopic follow-up examinations were carried out at 6-month intervals in the absence of recurrence or immediately if there was any recurrent bleeding. RESULTS: The mean physical injection points per session were 2.89 ± 0.79, and the mean volume of lauromacrogol used per session was 17.74 ± 7.09 ml in the bc-EIS group. The mean band per session was 6.13 ± 0.86. The rate of eradication after one to three rounds of bc-EIS was obviously higher than that of the EVL group (89.36%, 97.87%, and 100% vs. 37.5%, 43.75%, and 47.92%, respectively). Retrosternal pain or discomfort in the bc-EIS group was slightly lower than that in the EVL group (23.4%, 11/47 vs. 31.25%, 15/48). Two and five patients showed mild abdominal bloating and distension between the bc-EIS and EVL groups, respectively (2/47, 4.26% vs. 5/48, 10.42% P > 0.05). Nausea and vomiting were reported in one patient (1/47, 2.13%) in the bc-EIS group and three patients (3/48, 6.25%) in the EVL group. However, there were no statistically significant differences between the two groups (P > 0.05). No fatal or severe complications, such as esophageal perforation, esophageal stricture or ectopic embolism, were observed. CONCLUSION: The bc-EIS method was effective in eradicating EVs and was accompanied by fewer complications.

TaPR1 Interacts With TaTLP1 via the αIV Helix to Be Involved in Wheat Defense to Puccinia triticina Through the CAPE1 Motif.

Pathogenesis-related (PR) proteins play important roles in plant defense response and systemic acquired resistance (SAR). PR1 has antifungal activity against many plant pathogens. In our previous study, RNA sequencing (RNA-seq) was conducted on resistant wheat line TcLr19 and sensitive wheat cultivar Chinese Spring inoculated with Puccinia triticina (Pt) race PHNT. In this study, seven salicylic acid (SA)-induced TaPR1 genes involved in plant disease resistance were found in the RNA-seq library. Quantitative PCR (qPCR) results showed that TaPR1-4 was most induced by Pt among these seven TaPR1 genes in the incompatible interaction. Yeast two-hybrid (Y2H) results showed that TaPR1-4 interacted with TaTLP1 via the αIV helix. Protein-mediated phenotyping assays in vivo and antifungal activity in vitro demonstrated that wheat leaves infiltrated with pure TaPR1-4 protein developed significantly less disease compared to control leaves. This effect was correlated with a strong increase in defense gene expression, and resistance activity was dependent on the CAPE1 motif located in the C-terminal region of TaPR1-4. These findings increase current knowledge regarding the interaction of TaPR1 and TaTLP1 and provide new insights on the role of TaPR1 protein in the resistance of wheat to Pt.

Imaging Genetics in Epilepsy: Current Knowledge and New Perspectives.

Epilepsy is a neurological network disease with genetics playing a much greater role than was previously appreciated. Unfortunately, the relationship between genetic basis and imaging phenotype is by no means simple. Imaging genetics integrates multidimensional datasets within a unified framework, providing a unique opportunity to pursue a global vision for epilepsy. This review delineates the current knowledge of underlying genetic mechanisms for brain networks in different epilepsy syndromes, particularly from a neural developmental perspective. Further, endophenotypes and their potential value are discussed. Finally, we highlight current challenges and provide perspectives for the future development of imaging genetics in epilepsy.

Structural characterization of the urease accessory protein UreF from Klebsiella pneumoniae.

Klebsiella pneumoniae is an opportunistic pathogen that mostly affects those with weakened immune systems. Urease is a vital enzyme that can hydrolyze urea to ammonia and carbon dioxide as a source of nitrogen for growth. Urease is also a K. pneumoniae virulence factor that enables survival of the bacterium under nutrient-limiting conditions. UreF, an important nickel-binding urease accessory protein, is involved in the insertion of Ni2+ into the active site of urease. Here, the crystal structure of UreF from K. pneumoniae (KpUreF) is reported. Functional data show that KpUreF forms a stable dimer in solution. These results may provide a starting point for the design of urease inhibitors.

Balloon-compression endoscopic injection sclerotherapy for the treatment of esophageal varices.

Video 1Balloon-compression endoscopic injection sclerotherapy for the treatment of esophageal varices. A 50-year-old man with schistosomiasis-induced liver fibrosis presented with melena and hematemesis. The bleeding stopped after intravenous administration of somatostatin and ceftriaxone for 4 days. Balloon-compression endoscopic injection sclerotherapy (bc-EIS) was performed with the patient under general anesthesia to prevent rebleeding. The novel device for bc-EIS is composed of a syringe, a stopcock, a catheter, and an inflatable balloon. In the majority of patients with cirrhosis, the blood flow from the coronary vein drains into the azygos and hemiazygos venous system through esophageal and para-esophageal varices, and eventually back to the inferior vena cava. With compression of proximal esophageal and para-esophageal varices via an inflated balloon, sclerosant can be retained at the injection site, rather than flowing back to the inferior vena cava. Endoscopy revealed the presence of moderately enlarged, beady esophageal varices with red wale signs in the middle and lower esophagus. An inflatable balloon was fixed to an endoscope at a distance of 3 cm from its distal end. When the end of the endoscope was introduced to the target varices, 20 mL of air was injected into the balloon through a thin catheter, making its outer diameter expand to 3.5 cm. A disposable endoscopic injection needle then entered the base of the variceal columns near the cardia. When blood flowed back into the needle, a mixture of Lauromacrogol and methylene blue was intravariceally administered. Minor bleeding at the injection site was stopped through brief compression with the needle sheath. The second injection was performed following the aforementioned procedure. Follow-up endoscopy at 1 month, 4 months, and 7 months revealed the progression from thrombosed blue varices to complete eradication of esophageal varices. Endoscopic ultrasonography also showed the absence of blood flow in the varices after treatment. To date, bc-EIS has been performed successfully on 28 patients with esophageal varices. Variceal eradication was obtained in 17 patients with 1 session, 10 patients with 2 sessions, and 1 patient with 3 sessions. Two patients showed recurrence of esophageal varices on routine follow-up endoscopy and were re-treated with bc-EIS successfully. There were no severe complications during the follow-up period. With the sclerosant retained at injection sites after balloon compression, bc-EIS enables complete eradication of esophageal varices and lowers the risk of recurrence. The blockade of sclerosant also decreases the incidence of complications related to large-volume injection of sclerosant, such as embolization, ulceration, and perforation. In conclusion, bc-EIS appears to be an effective and safe approach for the treatment of esophaeal varices. Further research is underway to determine its suitability for large-scale clinical application.

Structure of Pseudomonas aeruginosa spermidine dehydrogenase: a polyamine oxidase with a novel heme-binding fold.

The opportunistic pathogen Pseudomonas aeruginosa can utilize polyamines (including putrescine, cadaverine, 4-aminobutyrate, spermidine, and spermine) as its sole source of carbon and nitrogen. Spermidine dehydrogenase (SpdH) is a component of one of the two polyamine utilization pathways identified in P. aeruginosa, but little is known about its structure and function. Here, we report the first crystal structure of SpdH from P. aeruginosa to 1.85 Å resolution. The resulting core structure confirms that SpdH belongs to the polyamine oxidase (PAO) family with flavin-binding and substrate-binding domains. A unique N-terminal extension wraps around the flavin-binding domain of SpdH and is required for heme binding, placing a heme cofactor in close proximity to the FAD cofactor. Structural and mutational analysis reveals that residues in the putative active site at the re side of the FAD isoalloxazine ring form part of the catalytic machinery. PaSpdH features an unusual active site and lacks the conserved lysine that forms part of a lysine-water-flavin N5 atom interaction in other PAO enzymes characterized to date. Mutational analysis further confirms that heme is required for catalytic activity. This work provides an important starting point for understanding the role of SpdH, which occurs universally in P. aeruginosa strains, in polyamine metabolism.

Screening, clinical features and prognostic analysis of liver cirrhosis-related hepatocellular carcinoma.

OBJECTIVE: To explore the impact of the screening interval and methods on cirrhosis-related hepatocellular carcinoma (HCC) detection and to analyse the clinical features and prognosis of HCC. MATERIALS AND METHODS: We recruited 3000 patients diagnosed with liver cirrhosis, who had been treated at the First Affiliated Hospital of Anhui Medical University from January 2016 to January 2020. The time of admission was divided into 3- (group A, 539 cases), 6- (group B, 1012 cases), and 12-month screening groups (group C, 1449 cases). We compared the detection rate of small HCCs in each group and analysed the clinical characteristics and prognosis of the patients with HCC. RESULTS: We detected a total of 124 HCC cases, including 41 cases of small HCC: 21, 14, and 6 cases in groups A, B, and C, respectively. The detection rate was 3.9% (21/539) in group A, which was significantly higher than that in groups B and C (χ2 = 31.186, p < .001). Single small, right liver lobe, and alpha-fetoprotein-negative HCCs accounted for 90.2%, 73.2%, and 68.3%, respectively. We detected vascular invasion and lymph node metastasis in one and three cases, respectively. The average survival time of patients in the small HCC group was significantly higher than that in the non-small-HCC group (35.68 ± 12.95 vs. 22.87 ± 11.42 months) (t = 5.623, p < .001). CONCLUSIONS: Screening patients with a history of liver cirrhosis at intervals of 3 months can increase the detection rate of small HCCs. Early detection can provide more patients with an opportunity for radical treatment and prolong their survival.

PPARγ induces PD-L1 expression in MSS+ colorectal cancer cells.

Only a small subset of colorectal cancer (CRC) patients benefits from immunotherapies, comprising blocking antibodies (Abs) against checkpoint receptor "programmed-cell-death-1" (PD1) and its ligand (PD-L1), because most cases lack the required mutational burden and neo-antigen load caused by microsatellite instability (MSI) and/or an inflamed, immune cell-infiltrated PD-L1+ tumor microenvironment. Peroxisome proliferator-activated-receptor-gamma (PPARγ), a metabolic transcription factor stimulated by anti-diabetic drugs, has been previously implicated in pre/clinical responses to immunotherapy. We therefore raised the hypothesis that PPARγ induces PD-L1 on microsatellite stable (MSS) tumor cells to enhance Ab-target engagement and responsiveness to PD-L1 blockage. We found that PPARγ-agonists upregulate PD-L1 mRNA/protein expression in human gastrointestinal cancer cell lines and MSS+ patient-derived tumor organoids (PDOs). Mechanistically, PPARγ bound to and activated DNA-motifs similar to cognate PPARγ-responsive-elements (PPREs) in the proximal -2 kb promoter of the human PD-L1 gene. PPARγ-agonist reduced proliferation and viability of tumor cells in co-cultures with PD-L1 blocking Ab and lymphokine-activated killer cells (LAK) derived from the peripheral blood of CRC patients or healthy donors. Thus, metabolic modifiers improved the antitumoral response of immune checkpoint Ab, proposing novel therapeutic strategies for CRC.

Removal of giant blood clots in patients with gastroesophageal variceal bleeding using novel methods: two case reports.

Gastroesophageal variceal bleeding is a severe complication of cirrhotic portal hypertension. Endoscopic treatment is recommended as the first-line therapy for gastroesophageal variceal bleeding, and its therapeutic effect is closely related to the visualization of endoscopy. We reported 2 cases of gastric variceal bleeding in which clear endoscopic visualization was obtained with two simple approaches assisted by suction tube and stone retrieval basket, respectively. Endoscopic treatments were successfully conducted after the removal of giant blood clots. Serious complications were not found.

Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice.

BACKGROUND: Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown. METHODS: In the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests. RESULTS: We found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group. CONCLUSIONS: These results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients.