Infected stent graft and severe aortitis after transcaval glue embolization of type II endoleak: a case report.

Background: Type II endoleaks are common and embolization is often performed if treatment is necessary. Although transarterial embolization is common, other methods including trans-caval embolization are also utilized. Complications can occur and we report a case of infection that was challenging to diagnose and treat. There is no data regarding the risk of aortic stent graft infection after trans-caval embolization with n-butyl 2-cyanoacrylate (n-BCA) glue of a type II endoleak. Case Description: We report a rare case of infected, Gore Excluder infrarenal stent graft after transcaval embolization with coil and n-BCA glue to treat a type II endoleak in a 71-year-old male. The endoleak caused a rapid sac enlargement. The stent graft was placed 5 years earlier electively. Soon after the endoleak embolization, the patient experienced abdominal pain and malaise. There was an intense inflammatory reaction involving the aneurysm wall and the adjacent bowel mesentery. Our differential included normal inflammation after embolization vs. infection and this was difficult to distinguish. The infection was confirmed by positron emission tomography scan and tissue biopsy. The patient was deemed high-risk for surgery because of his extensive cardiac history, status post coronary bypass and tissue mitral valve replacement, congestive heart failure with residual left ventricular ejection fraction of 36%. He was optimized by correcting fluid status, administration of intravenous antibiotic, and nutrition consultation with dietary supplementation before surgery over the course of 2 weeks. The graft was explanted through a transabdominal approach, and the aorta was reconstructed with cryopreserved allograft. Interestingly, the small and large intestine with their mesentery were found to be plastered to the aneurysm sac. The post-operative course was unremarkable except for a transient acute kidney injury that resolved within 1 week. Follow-up computed tomography scan at 6 months showed widely patent bypass. Conclusions: Glue embolization induces inflammation promoting thrombus formation inside the aneurysm sac. With a transcaval approach to the sac, there is the risk of extravasation of glue outside the sac as well as contamination of the graft with instrumentation. Differentiating between inflammation and infection can be difficult, and tissue biopsy provided the most conclusive diagnosis. Risk minimization considerations include, pre-operative optimization, a transabdominal approach, ureteral stenting, and tissue buttressing of anastomosis.

Exploring green environmental composites as hosts for shielding materials using experimental, theoretical and Geant4 simulation methods.

Rice straw is considered an agricultural waste harmful to the environment, which is abundant in most parts of the world. From this point, the present study is devoted to preparing new composites of two types of glue based on rice straw as a plentiful, low-cost matrix. Straw glue samples were prepared by mixing 20% wt. of rice straw with 80% wt. of animal glue (RS-An) and polyvinyl acetate (RS-PVAC) at different thicknesses of 1, 2, and 3 cm. The chemical composition of the prepared samples was identified by energy dispersive X-ray analysis and their morphology was examined using a scanning electron microscope. The mechanical test explored that RS-An and RS-PVAC respectively required a stress of 25.2 and 25.5 MPa before reaching the breaking point. γ-ray shielding performance was analyzed and determined at numerous photon energies from 0.059 to 1.408 MeV emitted from five-point γ-rays sources using NaI (Tl). Linear attenuation coefficient was calculated by obtaining the area under the peak of the energy spectrum observed from Genie 2000 software in the presence and absence of the sample. The experimental results of mass attenuation coefficient were compared with theoretical data of XCOM software with relative deviation ranging from 0.10 to 2.99%. Geant4 Monte Carlo simulation code was also employed to validate the experimental results. The relative deviation of XCOM and Geant4 outcomes was 0.09-1.77%, which indicates a good agreement between them. Other radiation shielding parameters such as half value layer (HVL), tenth value layer, and mean free path were calculated in three ways: experimentally, theoretically from the XCOM database, and by simulation using Geant4 code. Additionally, effective atomic number (Zeff), effective atomic number (Neff), equivalent atomic number (Zeq), and buildup factors were evaluated. It was confirmed that the γ-ray shielding properties were further boosted by mixing rice straw with the animal glue compared to the synthetic one.

Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics.

Targeted therapies, such as small molecule kinase inhibitors, have made significant progress in the treatment of hematologic malignancies by directly modulating protein activity. However, issues such as drug toxicity, drug resistance due to target mutations, and the absence of key active sites limit the therapeutic efficacy of these drugs. Targeted protein degradation (TPD) presents an emergent and rapidly evolving therapeutic approach that selectively targets proteins of interest (POI) based on endogenous degradation processes. With an event-driven pharmacology of action, TPD achieves efficacy with catalytic amounts, avoiding drug-related toxicity. Furthermore, TPD has the unique mode of degrading the entire POI, such that resistance derived from mutations in the targeted protein has less impact on its degradation function. Proteolysis-targeting chimeras (PROTACs) and molecular glue degraders (MGDs) are the most maturely developed TPD techniques. In this review, we focus on both preclinical experiments and clinical trials to provide a comprehensive summary of the safety and clinical effectiveness of PROTACs and MGDs in hematologic malignancies over the past two decades. In addition, we also delineate the challenges and opportunities associated with these burgeoning degradation techniques. TPD, as an approach to the precise degradation of specific proteins, provides an important impetus for its future application in the treatment of patients with hematologic malignancies.

An annotated image dataset of pests on different coloured sticky traps acquired with different imaging devices.

The sticky trap is probably the most cost-effective tool for catching insect pests, but the identification and counting of insects on sticky traps is very labour-intensive. When investigating the automatic identification and counting of pests on sticky traps using computer vision and machine learning, two aspects can strongly influence the performance of the model - the colour of the sticky trap and the device used to capture the images of the pests on the sticky trap. As far as we know, there are no available image datasets to study these two aspects in computer vision and deep learning algorithms. Therefore, this paper presents a new dataset consisting of images of two pests commonly found in post-harvest crops - the red flour beetle (Tribolium castaneum) and the rice weevil (Sitophilus oryzae) - captured with three different devices (DSLR, webcam and smartphone) on blue, yellow, white and transparent sticky traps. The images were sorted by device, colour and species and divided into training, validation and test parts for the development of the deep learning model.

Tissue Adhesive versus Skin Suture plus Waterproof Wound Dressings for Carpal Tunnel Wound Closure: A Prospective Randomized Controlled Trial.

Introduction: The popular wound closure methods for carpal tunnel decompression (CTD) include non-absorbable and absorbable sutures which have comparable results in clinical outcomes. However, these wound closure methods are recommended to keep a wound dry which may limit some ADLs. We conducted a prospective randomized controlled trial that compares clinical outcomes and cost-effectiveness in a skin closure following CTD between absorbable sutures plus a 2-octyl cyanoacrylate tissue adhesive (2OCA) versus non-absorbable skin sutures plus a waterproof dressing (NSPWD). Materials and Methods: We enrolled 120 patients undergoing CTD into two groups: 2OCA and NSPWD, with 60 patients in each group. Number of dressing changes, Quick DASH, pain VAS, cosmetic VAS, patient satisfaction VAS, and Hollander wound evaluation score, cost-effectiveness, and post-operative complications were collected at pre-operative period and two and six weeks post-operatively. Results: Slightly better patient satisfaction VAS (7.9 vs 7.2, p=0.018) and cosmetic VAS (8.0 vs 7.2, p=0.025) were observed in 2OCA at 2 weeks. Meanwhile, NSPWD revealed lesser times of dressing change (Median, mode, IQR: 0/0/0 vs 2/3/2, p<0.001). The total wound-related costs include dressing change and suture removal cost ($15.9 for 2OCA vs $19.2 for NSPWD, p=0.002) although an initial wound-related cost in 2OCA was higher ($15.7/case vs $7.9/case, p<0.001). Conclusion: Our study revealed that the supplementary tissue adhesive to absorbable sutures following CTD could reduce total wound-related costs while clinical outcomes might not be considered clinically significant.

Amniotic membrane graft to patch an overfiltering trabeculectomy flap.

Purpose: To describe the use of an amniotic membrane graft (AMG) with fibrin sealant to address an overfiltering trabeculectomy flap encountered intraoperatively. Observations: A 35-year-old female with severe primary open angle glaucoma underwent trabeculectomy with mitomycin C due to uncontrolled intraocular pressure (IOP). Intraoperatively, the elastic nature of the scleral flap led to overfiltration, causing persistent anterior chamber shallowing despite numerous sutures. To decrease but not completely shut down aqueous outflow through the trabeculectomy flap, we utilized AMG and fibrin sealant to stabilize the flap. Postoperatively, the patient had a formed anterior chamber, elevated bleb and significantly reduced IOP, without the need for additional glaucoma medications. Conclusions and importance: Amniotic membrane grafts (AMG) with fibrin sealant may help regulate aqueous flow efflux, maintain anterior chamber stability, and mitigate the risk of postoperative hypotony in trabeculectomy surgery. AMG was chosen in this setting given its anti-inflammatory, anti-fibrotic properties, as well as its optically clear nature to allow for post-operative visualization of the flap. AMG allows for early postoperative stabilization of the scleral flap without complete obstruction, and may be useful in patients at risk of early postoperative hypotony.

Perspective: Timely diagnosis and repair of intraoperative thoracic/lumbar cerebrospinal fluid (CSF) leaks.

Background: Our review of 12 articles for this perspective showed the frequency of intraoperative thoracic and/or lumbar CSF fistulas/dural tears (DT) ranged from 2.6% - 8% for primary surgical procedures. Delayed postoperative CSF leak/DT were also diagnosed in 0.83% (17/2052 patients) to 14.3% (2/14 patients) of patients undergoing thoracic and/or lumbar procedures. Further, the rate of recurrent postoperative CSF leaks/DT varied from 13.3% (2/15 patients) to 33.3% (4/12 patients). Methods: Intraoperative, postoperative delayed, and recurrent postoperative traumatic postsurgical thorac CSF leaks/DT can be limited by performing initially sufficient operative decompressions and/or decompressions/fusions (i.e., utilizing adequate open exposures vs. inadequate minimally invasive (MI) approaches). The incidence of CSF leaks/DT can be further reduced by spine surgeons' utilization of operating microscopes, and their avoiding routine attempts at total synovial cyst excision and/or complete resection of hypertrophied/ossified yellow ligament in the presence of significant dural adhesions. Results: Multiple CSF leak/CT repair techniques included; using interrupted, non-resorbable sutures for direct dural repairs (i.e. 7-0 Gore-Tex sutures where the suture is larger than the needle thus plugging needle holes), and adding where needed muscle patch grafts, microfibrillar collagen, the rotation of Multifidus muscle pedicle flaps, fibrin sealants (FS)/fibrin glues (FG), lumbar drains (LD), and/or lumbo-peritoneal (LP) shunts. Conclusion: Intraoperative, postopertive delayed, and/or recurrent postoperative thorac and/or lumbar traumatic surgical CSF leaks can be reduced by choosing to initially perform the appropriately extensive open operative decompressions and/or decompresssions/fusions. It is critical to use an operating microscope, non-resorbable interrupted sutures, and where necessary, muscle patch grafts, microfibrillar collagen, the rotation of Multifidus Muscle Pedicle Flaps, FS/FG, LD, and/or LP shunts.

Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression.

Background: Velcrins are molecular glues that kill cells by inducing the formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. Formation of the complex activates SLFN12, which cleaves tRNALeu(TAA) and induces apoptosis. Velcrins such as the clinical investigational compound, BAY 2666605, were found to have activity across multiple solid tumor cell lines from the cancer cell line encyclopedia, including glioblastoma cell lines. We therefore aim to characterize velcrins as novel therapeutic agents in glioblastoma. Materials and Methods: PDE3A and SLFN12 expression levels were measured in glioblastoma cell lines, the Cancer Genome Atlas (TCGA) tumor samples, and tumor neurospheres. Velcrin-treated cells were assayed for viability, induction of apoptosis, cell cycle phases, and global changes in translation. Transcriptional profiling of the cells was obtained. Xenograft-harboring mice treated with velcrins were also monitored for survival. Results: We identified several velcrin-sensitive glioblastoma cell lines and 4 velcrin-sensitive glioblastoma patient-derived models. We determined that BAY 2666605 crosses the blood-brain barrier and elicits full tumor regression in an orthotopic xenograft model of GB1 cells. We also determined that the velcrins BAY 2666605 and BRD3800 induce tumor regression in subcutaneous glioblastoma PDX models. Conclusions: Velcrins have antitumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents.

Results of patch testing propolis in the European baseline series: A 4-year retrospective study.

BACKGROUND: Propolis was added to the European baseline series (EBS) in 2019. OBJECTIVES: To investigate the frequency and relevance of positive patch tests to propolis in the EBS and to study co-reactivities. PATIENTS AND METHODS: Retrospective study in patients patch tested between June 2019 and November 2023 in a university hospital in Amsterdam, The Netherlands. RESULTS: Of 3134 consecutive patients, 299 (9.5%) had a positive reaction to propolis 10% pet. Only nine reactions (3%) were judged to be clinically relevant. There were significant co-reactivities to Myroxylon pereirae resin (balsam of Peru), colophonium, fragrance mixes 1 and 2, and to limonene and linalool hydroperoxides. A steep increase in rates of positive reactions to propolis was observed from 2020 to 2023. This was highly likely the result of the replacement of Chinese propolis with Brazilian propolis by the manufacturer. CONCLUSIONS: Positive patch tests for propolis are very frequent in Amsterdam, but only a few of these reactions are relevant. Most are probably (pseudo-)cross-reactions in patients with fragrance allergies. Propolis in the EBS has very limited value for dermatologists and patients in The Netherlands. Changes in patch test materials should be provided to all users to avoid misinterpretation of patch test results.

Comparison of nylon, vicryl, and fibrin glue for nerve grafting in rats.

OBJECTIVES: For nerve injuries, not amendable to tensionless epineural coaptation of the nerve, autografts are the preferred treatment. Although absorbable sutures are not recommended for nerve repair, there is no evidence that non-absorbable sutures are superior to absorbable sutures. This study aims to assess the effectiveness of non-absorbable monofilament nylon sutures, absorbable monofilament vicryl sutures, and fibrin glue when used for nerve grafting. METHODS: Lewis rats (N = 32) were subjected to a sciatic nerve transection and randomly assigned to a group: graft with Nylon, graft with Vicryl, graft with Fibrin Glue, or no graft. Motor function, sensory function, and thermal pain were assessed during a 12-week recovery period, and immunohistochemistry was used to assess macrophage response. RESULTS: At 12 weeks, the Vicryl and Nylon groups had significantly larger ankle angles at to lift off, which is a measure of motor function, compared to injured controls (p < 0.05). Grafted rats displayed no difference in thermal response but hypersensitivity to mechanical stimuli compared to the uninjured hindlimb. The Nylon, Vicryl, and Fibrin Glue groups all had significantly less atrophy of the gastrocnemius muscle compared to injured controls (p < 0.0001). In the Fibrin Glue group, 3/9 grafts did not incorporate. The Nylon group had significantly less (p = 0.0004) axon growth surrounding the suture holes compared to the Vicryl group. There were no differences in the axon counts, motor neurons, or sensory neurons between all grafted rats. CONCLUSIONS: These results demonstrate that vicryl sutures work just as well as nylon for nerve recovery after injury and grafting.

Data on terpene content in pre-rolled cone paper infused with terpene-containing flavours based on the formation of a partially soluble precipitate.

The high volatility of the terpenes contained in flavour-containing terpene (FCT) products causes the loss of these contents during product storage; thus, measuring the loss of FCT content during storage is important to estimate the final content. This work provides data on the reduction in FCT content of infused pre-rolled paper cones after 1 to 7 days of storage. Determination of FCT content was based on the formation of a reddish-brown precipitate resulting from the reaction of terpene moiety in FCT with sulphuric acid. Then, the absorbance of the precipitate was analysed using the UV-Vis Spectrophotometric method at a visible wavelength of 538 nm. A calibration standard curve was prepared concerning the concentration of the original FCT sample and used to determine the FCT content in infused pre-rolled paper. The FCT content on the first day of storage decreased and increased again after seven days of storage due to condensation. The data on the FCT content reduction as the effect of additive added was also evaluated.

Minimally Invasive Endovascular Management of Uterine Arteriovenous Malformations: A Single Center Experience and Case Series.

Uterine arteriovenous malformations (UAVMs) are rare and abnormal entanglements of uterine arteries and veins that are potentially fatal, requiring blood transfusions in about a third of cases. Although the optimal management of the condition is not well established in the literature, surgical hysterectomy is believed to be the only definitive treatment for arteriovenous malformations. We present three cases of UAVMs treated by a minimally invasive endovascular approach. Chief complaints were heavy menstrual bleeding and sudden onset heavy bleeding. The diagnosis was confirmed by computed tomography imaging and angiography of the pelvic vessels. Uterine artery embolization (UAE) was performed in all patients. The follow-up period was uneventful. In our experience, the UAE provides satisfactory results in terms of success rates, complications, and short hospital stays.

Antimicrobial peptide-fibrin glue mixture for treatment of methicillin-resistant Staphylococcus aureus-infected wounds.

Aim: This study was conducted to investigate the effect of fibrin glue-CM11 antibacterial peptide mixture (FG-P) on the healing of infected wounds in vivo. Materials & methods: We formulated a mixture of FG-P and evaluated its antimicrobial activity in vitro against multidrug-resistant (MDR) bacteria involved in wound infection as well as its healing effect on wound infected by methicillin-resistant S. aureus (MRSA) in vivo. Results: The peptide had an MIC of 8 µg/ml against all bacteria isolates. Growth inhibition zones were evident for FG-P compared with FG. The in vivo study showed that the FG-P could be significantly effective in healing the MRSA-infected wound. Conclusion: The use of FG-P mixture is a very suitable option for treating infected wounds.

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Scalable and Sustainable Zinc (II) Ions Glue Assisted Conversion of Biomass Waste Bits into Carbon Aerogels for Efficient Uranium Extraction.

Carbon aerogels (CAs) are attracting great attention for their multifunctional applications. Additionally, a large amount of biomass bits waste generated from agriculture and industry is regarded as the main carbon resource. However, the development of a facile, sustainable, and efficient method to produce CAs from biomass waste remains challenging. Here, a one-step Zn2+ ions glue triggered carbonization technology was reported to construct large-scale and high-performance CAs. Multiple biomass bits (wood bits, peanut shells, bamboo bits, and straw waste) were treated in the molten salt system (ZnCl2/KCl) at 300 °C for 2h to obtain large-block biomass bits derived CAs. Zn2+ ions as the glue cleavage cellulose hydrogen bonds of natural biomass, then facilitate dehydration crosslinking reaction between cellulose, hemicellulose, and lignin for re-constructing the whole block structure. The obtained CAs show high porosity (95%) and low density (0.078 g/cm3). Meanwhile, numerous of hydroxyl and carbonyl groups were well maintained during low temperature treated process, which facilitate chemical modification for various applications. For instance, amidoxime functionalized CAs were utilized as a filter for selective and highly efficient extraction of U(VI) from wastewater. The adsorption capacity and extraction efficiency reached 801.2 mg/g and 95% with a flux rate of 6.1×103 L/m2·h, respectively.

The use of Fibrin Sealants in Reducing Drain Output in Abdominoplasty: Is it Useful?

Background: Abdominoplasty is a common surgical procedure in which excess abdominal skin and fat are reduced to improve body contouring. Fibrin sealant has been proposed to reduce postsurgical bleeding and exudation. In this study, we evaluated whether there was a significant statistical difference in surgical output between the use of fibrin glue and its nonuse in abdominoplasty surgery, specifically in reducing bleeding and exudation. Material and methods: A retrospective chart review of 68 postbariatric abdominoplasty patients (58 females, 10 males) was performed. We divided the patients into Group A (30 cases, 44%), in which we used fibrin sealant, and Group B (38 cases, 56%), in which we did not use fibrin glue. We calculated the total amount of liquid in suction drainages until the day of their removal. Statistical analysis included the independent t-test with a significance level of 0.05. Results: The average drainage output in Group A was 620.0 ± 375.0 mL, whereas in Group B, it was 500.0 ± 290.0 mL. Results indicate an insignificant correlation between the use of fibrin glue and the amount of liquid in the surgical drains (t = 1.52, p = 0.13). The result is not significant at p <.05 according to the independent t-test. Conclusion: The use of fibrin sealant surely has a high value in all surgical branches to reduce postoperative complications, but in our study, we did not find any advantages in its use for reducing surgical drain output in abdominoplasty patients.

Comparative analysis of medical glue and positioning hooks for preoperative localization of pulmonary nodules.

Background: Through preoperative localization, surgeons can easily locate ground glass nodules (GGNs) and effectively control the extent of resection. Therefore, it is necessary to choose an appropriate puncture positioning method. The purpose of this study was to evaluate the effectiveness and safety of medical glue and positioning hooks in the preoperative positioning of GGNs and to provide a reference for clinical selection. Methods: From March 30, 2020 to June 13, 2022, a total of 859 patients with a CT diagnosis of GGNs requiring surgical resection were included in our study at the hospital. Among them, 21 patients who either opted out or could not undergo preoperative localization for various reasons were excluded. Additionally, 475 patients who underwent preoperative localization using medical glue and 363 patients who underwent preoperative localization through positioning hooks were also excluded. We conducted statistical analyses on the baseline data, success rates, complications, and pathological results of the remaining patients. The success rates, complication rates, and pathological results were compared between the two groups-those who received medical glue localization and those who received positioning hook localization. Results: There was no statistically significant difference between the two groups of patients in terms of age, body mass index, smoking history, location of the nodule, distance of the nodule from the pleura, or postoperative pathological results (P > 0.05). The success rate of medical glue and positioning hooks was 100%. The complication rates of medical glue and positioning hooks during single nodule positioning were 39.18% and 23.18%, respectively, which were significantly different (p < 0.001); the complication rates during multiple nodule positioning were 49.15% and 49.18%, respectively, with no statistically significant differences (p > 0.05). In addition, the method of positioning and the clinical characteristics of the patients were not found to be independent risk factors for the occurrence of complications. The detection rate of pulmonary nodules also showed some positive correlation with the spread of COVID-19 during the 2020-2022 period when COVID-19 was prevalent. Conclusion: When positioning a single node, the safety of positioning hooks is greater than when positioning multiple nodes, the safety of medical glue and positioning hooks is comparable, and the appropriate positioning method should be chosen according to the individual situation of the patient.

Comparison of Fibrin Glue With Conventional Suturing in Peripheral Nerve Repairs: A Study of Sensory and Motor Outcomes.

BACKGROUND: Nerve injuries have traditionally been repaired with sutures, and this method is considered the gold standard technique in the management of nerve injuries. However, fibrin glue has recently become a promising tool for repairing nerve injuries and has advantages including ease of usability, atraumatic application technique, and decreased co-optation time of the nerves. This study aims to clinically evaluate the efficacy of nerve repair with fibrin glue compared with the usual suture technique in terms of sensory and motor outcomes. METHODS: A total of 80 patients were included in the study; 50 patients underwent primary nerve repair, and 30 patients underwent Oberlin's repair. These subsets were randomly divided into two groups in which the nerves were repaired with microsutures in one group and fibrin glue in the other group. RESULTS: In the comparison of fibrin glue with microsutures, there were no significant differences between the two groups in the 2-point discrimination (2PD) test, Semmes-Weinstein test, motor function, and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire scores. However, the co-optation times were significantly shorter with fibrin glue than with microsutures. CONCLUSION: Based on our findings, nerve repair with fibrin glue is as effective as microsutures in terms of sensory and motor recovery and has added advantages of ease of usability and shorter repair times. Therefore, fibrin glue may be an effective alternative to sutures in nerve repair.

The next-generation KRAS inhibitors What comes after sotorasib and adagrasib?

The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the first driver oncogenes identified in human cancer in the early 1980s. However, it has been deemed 'undruggable' for nearly four decades until the discovery of KRAS G12C covalent inhibitors, which marked a pivotal breakthrough. Currently, sotorasib and adagrasib have been approved by the US FDA to treat patients with non-small cell lung cancer (NSCLC) harboring KRAS G12C mutation. However, their efficacy is somewhat limited compared to that of other targeted therapies owing to intrinsic resistance or early acquisition of resistance. While G12C is the predominant subtype of KRAS mutations in NSCLC, G12D/V is prevalent in colorectal and pancreatic cancers. These facts have spurred active research to develop more potent KRAS G12C inhibitors as well as inhibitors targeting non-G12C KRAS mutations. Novel approaches, such as molecular shielding or targeted protein degradation, are also under development. Combining KRAS inhibitors with inhibitors of the receptor-tyrosine kinase-RAS-mitogen-activated protein kinase (MAPK) pathway is underway to counteract redundant feedback mechanisms. Additionally, immunological approaches utilizing T-cell receptor (TCR)-engineered T cell therapy or vaccines, and Hapimmune antibodies are ongoing. This review delineates the recent advancements in KRAS inhibitor development in the post-sotorasib/adagrasib era, with a focus on NSCLC.

Chinese herbal formula, modified Guilu Erxian glue, alleviates apoptosis of hematopoietic stem cells by regulating SLAM-SAP signal pathway in aplastic anemia mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Guilu Erxian Glue (GEG) and Danggui Buxue Tang (DBT) are traditional Chinese herbal formulas. According to the theory of traditional Chinese medicine, the combination of those two formulas (Modified Guilu Erxian Glue, MGEG) has the effects of tonifying the kidney and producing blood, was usually used to treat bone marrow failure diseases, including aplastic anemia (AA). AIM OF THE STUDY: T lymphocytes play a crucial role in the disease pathogenesis and progression of AA. Our preliminary results confirmed that GEG can improve the damage of hematopoietic stem cells in mice, while DBT can reduce the proliferation and differentiation of T lymphocytes and inhibit the production of IFN-γ. We hypothesized that the combination of those two herbal formulas could inhibit immune attack and restore hematopoietic function through multiple mechanisms. In this study, we aim to study the curative effect of MGEG on regulating the expression of Signal lymphocyte activating molecule (SLAM), an activation-related molecule in T lymphocytes, thereby suppressing the immune function of T cells and decelerating the damage to hematopoietic stem cells. MATERIALS AND METHODS: High-performance liquid chromatography-electrospray ionization/mass spectrometry system was used to identify the components of the MGEG formulation. Induction of aplastic anemia mouse model by injecting allogeneic lymphocyte suspension into BABL/c mice after ionizing radiation. Cyclosporine A (CsA) was used as a positive control drug. Flow cytometry was used to detect the number and apoptosis rate of hematopoietic stem cells in the bone marrow. Enzyme-linked immunosorbent assay was performed to measure the levels of IFN-γ and TNF-α. Immunofluorescence staining was used to assess the expression of T-bet and SLAM-SAP. Western Blot was conducted to examine the expression of activation-related molecules in T lymphocytes and proteins related to the Fas signal pathway. Hematoxylin-eosin staining was performed to observe pathological changes in the bone marrow tissue. Wright-Giemsa staining was utilized to evaluate alterations in the cellular composition and basic structure of the bone marrow cells (BMCs). Transmission electron microscopy was employed to observe changes in the structure and morphology of hematopoietic stem cells. The hematology analyzer was used to detect peripheral blood parameters. RESULTS: Twenty-three different components were identified in MGEG. After MGEG treatment, the expression levels of Fyn and SLAM-SAP binding were increased in AA mice, while the expression levels of T-bet were decreased and the secretion of IFN-γ was reduced significantly. Additionally, MGEG also could downregulate the protein levels of Fas, caspase-3, and cleaved caspase-3 in AA mice. CONCLUSION: MGEG could attenuate the production of IFN-γ by promoting the SLAM-SAP signal pathway to regulate the generation and distribution of T-bet in T cells. Additionally, it suppresses apoptosis of HSCs through intervention in the Fas-dependent pathway, thereby mitigating immune-mediated damage to HSCs.

Trans-splenic percutaneous glue embolization of bleeding gastric varices in the setting of malignant sinistral portal hypertension.

Sinistral portal hypertension, also known as left-sided portal hypertension, is a rare cause of gastric variceal bleeding which occurs secondary to occlusion of the splenic vein. We present a case of venous occlusion and sinistral portal hypertension secondary to distal pancreatic cancer requiring treatment of gastric variceal bleeding. After failing conservative management, transvenous intervention was attempted, but a venous communication with the gastric varices was unable to be identified on multiple venograms. A percutaneous trans-splenic approach using a 21-G needle and ultrasound guidance was successful in directly accessing an intraparenchymal vein feeding the gastric varices, and glue embolization was performed directly through the access needle with excellent results.