Survival Period Research Articles

Evaluation of Neuroprotective Effects of Local Hypothermia in a Porcine Spinal Cord Injury Model

Abstract The goal of this study was to assess the therapeutic potential of a 5-hour local spinal cord (SC) hypothermia by 4 °C saline on preservation of SC tissue at the injury epicentre and 3 cranial and caudal 10 mm long SC segments in a porcine experimental model of spinal cord injury (SCI). The SCI was inflicted through L3 laminectomy by a metallic rod moved by a velocity of 30 mm.sec−1, and operated by a computer-controlled apparatus. A group of 15 female minipigs 5‒8-month-old weighing 28‒35 kg was randomly divided into 5 subgroups (each composed of 3 animals): 1) sham controls; 2) SCI by force 8N; 3) SCI by force 8N, 5-hour hypothermia; 4) SCI by force 15N; 5) SCI by force 15N, 5-hour hypothermia. After a 9-week survival period, the minipigs were in deep general anaesthesia transcardially perfused by 5000 ml of saline and fixed by 5000 ml 4 % neutral paraformaldehyde. White and grey SC matter damage was evaluated in specimens cut from the epicentre of injury as well as 3 cranial and 3 caudal 10 mm long SC blocks dyed according to Luxol fast blue (LFB) with cresyl violet (CV) protocol for light microscopic observations. The percentage of preserved SC white and grey matter was assessed in microphotographs and compared with data from sham controls (considered 100 %). The data were statistically evaluated by ANOVA test, the difference P ˂ 0.05 was considered significant. Results of the study suggest that 5-hour local cooling of the epicentre of SCI is well tolerated and facilitates the preservation of SC tissue integrity. Additional experimental and preclinical studies are necessary before introducing the method in practice.

Integrated bioinformatics analysis and validation identify KIR2DL4 as a novel biomarker for predicting chemotherapy resistance and prognosis in colorectal cancer

BackgroundChemotherapy and immunotherapy have improved the cure rate and survival period for colorectal cancer (CRC), but genetic heterogeneity among patients leads to chemotherapy resistance and disease progression. Identifying new molecular markers is crucial for improving prognosis for CRC patients. KIR2DL4, a transmembrane glycoprotein expressed by immune cells, has shown potential therapeutic and prognostic value in other cancers, but in CRC remains unclear. MethodsThis study validated the expression levels of KIR2DL4 in CRC by integrating multiple public databases and assessed through immunohistochemistry (IHC). We further evaluated the diagnostic and prognostic value of KIR2DL4 and explored correlation with immune cell infiltration and chemotherapy sensitivity. The role of KIR2DL4 was further validated through functional enrichment analysis. Cellular assays were conducted using CCK8, colony-formation assay and scratch wound assay. ResultsThe study found that KIR2DL4 is significantly downregulated in CRC and closely associated with poor prognosis. The low expression of KIR2DL4 is associated with decreased immune cell infiltration and reduced chemotherapy sensitivity. Functional enrichment analysis suggests that KIR2DL4 may inhibit development of CRC by affecting immune cell infiltration and modulating chemotherapy sensitivity. Cellular assays have confirmed that inhibiting KIR2DL4 significantly promotes the proliferation and migration of CRC. Inhibition of KIR2DL4 expression significantly decreased the chemosensitivity of CRC cells to oxaliplatin and 5-FU. ConclusionThe significant downregulation of KIR2DL4 in CRC, associated with CRC metastasis and poor prognosis, highlights its importance as a potential new biomarker for treatment and prognosis assessment of CRC. Future research should delve into the molecular mechanisms of KIR2DL4 and potential applications in regulating immunotherapy and chemotherapy sensitivity.

Exploration of Active Ingredients, Targets, and Potential Mechanisms of Er-Miao-San in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology

Background Er-Miao-San (EMS) is a classic prescription in Traditional Chinese Medicine (TCM) for the treatment of colorectal cancer (CRC) and has shown promising therapeutic effects in clinical practice. However, the specific components and molecular mechanisms of EMS remain unclear. Purpose The aim of this study was to analyze the effective components and molecular mechanisms of EMS in treating CRC through network pharmacology techniques and experimental validation. Materials and Methods The Traditional Chinese Medicine Systems Pharmacology database was used to screen the main active chemical components and targets of the EMS formula. The compound structures were verified using the PubChem database, which is an organic small-molecule bioactivity database. GeneCards and OMIM databases were utilized to predict target genes related to CRC. The Cytoscape 3.8 software was used to construct a “Drug-Active Ingredient-Target-Disease” intersection network. The STRING database was employed to analyze the core target protein–protein interaction network shared by EMS and CRC. The core targets were further subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the R language. Molecular docking between the core targets and the major active chemical components of EMS was performed using AutoDock software. The impact of the core targets on the prognosis of CRC patients was analyzed using the R language. Subsequently, we validated the potential mechanisms predicted by network pharmacology for the inhibition of CRC cell proliferation by the key proteins in the relevant pathways through CCK8 cell proliferation assays and Western blot experiments. Results Molecular docking results showed good docking affinity between the key active components, such as quercetin and baicalein, of EMS and the core targets. Kaplan–Meier survival analysis demonstrated a close correlation between the core targets and the survival prognosis of CRC patients. Cellular experiments showed that EMS significantly inhibited the proliferation of CRC cells and may promote apoptosis and autophagy of CRC cells by suppressing the expression of key proteins in the PI3K/AKT pathway. Conclusion The TCM formula EMS exerts anti-CRC effects through multiple pathways and targets, improving the prognosis and extending the survival period of CRC patients. This study provides preliminary insights into the effective components and molecular mechanisms of EMS in the treatment of CRC, which were preliminarily validated through molecular docking and experimental approaches.

Tiaogan Bushen Xiaoji Formula Enhances the Sensitivity of Estrogen Receptor- Positive Breast Cancer to Tamoxifen by Inhibiting the TGF-β/SMAD Pathway.

The resistance to endocrine therapy can lead to recurrence and metastasis of breast cancer (BC), affecting the survival period. Tiaogan Bushen Xiaoji (TGBSXJ) Formula, a traditional Chinese medicine (TCM) decoction, has been widely used in the treatment of estrogen receptor-positive (ER+) BC. However, the underlying mechanism of TGBSXJ Formula in ER+BC treatment has not been totally elucidated. Network pharmacology (NP) and RNA sequencing were used to predict the candidate ingredients and explore the potential targets of TGBSXJ Formula. Then, the results of NP and RNA sequencing were investigated by in vitro experiments. Active ingredients of TGBSXJ Formula mainly included Mangiferin, Rutin, Anemarrhena asphodeloides saponin BII, Ganoderic acid A and Acacetin, etc. A protein-protein interaction (PPI) network was created based on the active ingredients of TGBSXJ Formula and target genes of ER+ BC, in which TGF-β, MMP2 and SMAD3 were defined as the hub genes. In vitro experiments showed that TGBSXJ Formula significantly inhibited the viability, colony ability and migration of ER+ BC cells, and significantly increased the sensitivity to TAM. Western blot analysis showed that TGBSXJ Formula significantly downregulated TGF-β, E-cadherin, MMP2, MMP9, N-cadherin, p-Smad2 and p-Smad3 in ER+ BC cells. TGBSXJ Formula increases the sensitivity of ER+ BC cells to TAM by inhibiting the TGF-β/Smad signaling pathway.

Factors associated with cause-specific discontinuation of long-term anti-tumor necrosis factor agent use in patients with ankylosing spondylitis: a retrospective cohort study

ObjectTo investigate the factors associated with cause-specific discontinuation of long-term anti-tumor necrosis factor (TNF) agent use in patients with ankylosing spondylitis (AS).MethodsAS patients who initiated first-line anti-TNF treatment between 2004 and 2018 and continued treatment for at least two years were enrolled in the study. Enrolled patients were observed until the last visit, discontinuation of treatment, or September 2022. Reasons for discontinuation of the first-line anti-TNF agent were categorized into the following: (1) clinical remission, (2) loss of efficacy, (3) adverse events, and (4) other reasons including loss to follow-up, cost, or reimbursement issues. A cumulative incidence function curve was used to visualize the cumulative failure rates over time for each specific reason. Univariable and multivariable cause-specific hazard models were utilized to identify factors associated with cause-specific discontinuation of the first-line anti-TNF agent.ResultsA total of 429 AS patients was included in the study, with 121 treated with adalimumab (ADA), 176 with etanercept (ETN), 89 with infliximab (INF), and 43 with golimumab (GLM). The median overall survival on the first-line anti-TNF agent was 10.6 (7.9–14.5) years. Among the patients, 103 (24.0%) discontinued treatment, with 36 (34.9%) due to inefficacy, 31 (30.1%) due to clinical remission, 15 (14.6%) due to adverse events, and 21 (20.4%) due to other reasons. Patients treated with ETN had a lower risk of discontinuation due to clinical remission compared to those receiving ADA (hazard ratio [HR] 0.45 [0.21–0.99], P = 0.048). Higher baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; HR 1.31 [1.04–1.65], P = 0.023) and INF use were linked to a higher risk of treatment discontinuation for inefficacy compared to ADA use (HR 4.53 [1.45–14.16], P = 0.009). Older age was related to an increased risk of discontinuation due to infection-related adverse events (HR 1.07 [1.02–1.12], P = 0.005), and current smoking was a risk factor for discontinuation due to other reasons (HR 6.22 [1.82–21.28], P = 0.004).ConclusionAS patients on their first anti-TNF treatment for at least two years demonstrated a favorable long-term treatment retention rate, with a 24.0% discontinuation rate over a 10.6-year overall survival period. The predictors for discontinuation varied by causes, underscoring the complexity of treatment response and the importance of personalized approaches to treatment management.

Brief Discussion on the Efficacy of Combining Yiqi-jianpi Therapy with Chemotherapy for the Treatment of Colorectal Cancer

Colorectal cancer is one of the common and frequently occurring malignant tumors both at home and abroad. With the continuous economic development and improvement of living standards, the incidence of colorectal cancer has increased significantly due to the increasing prevalence of high-salt, high-fat, low-fiber diet. In recent years, the combination of Yiqi-jianpi therapy with chemotherapy for colorectal cancer has achieved better objective efficacy, and it has unique advantages in reducing toxicity, enhancing efficacy, improving the quality of life of patients, and prolonging survival period.

Combined targeting of Hedgehog/GLI1 and Wnt/β-catenin pathways in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. Challenges in its treatment include relapse, drug resistance, and a short survival period. The Hedgehog/GLI1 (Hh/GLI1) and Wnt/β-catenin pathways are crucial in cancer cell proliferation, survival, and drug resistance, making them significant targets for anticancer research. This study aimed to assess the effectiveness of combining inhibitors for both pathways against MCL and investigate the underlying molecular mechanisms. The co-expression of key proteins from the Hh/GLI1 and Wnt/β-catenin pathways was observed in MCL. Targeting the Hh/GLI1 pathway with the GLI1 inhibitor GANT61 and the Wnt/β-catenin pathway with the CBP/β-catenin transcription inhibitor ICG-001, dual-target therapy was demonstrated to synergistically suppressed the activity of MCL cells. This approach promoted MCL cell apoptosis, induced G0/G1 phase blockade, decreased the percentage of S-phase cells, and enhanced the sensitivity of MCL cells to the drugs adriamycin and ibrutinib. Both GANT61 and ICG-001 downregulated GLI1 and β-catenin while upregulating GSK-3β expression. The interaction between Hh/GLI1 and Wnt/β-catenin pathways was mediated by GANT61-dependent Hh/GLI1 inhibition. Moreover, GLI1 knockdown combined with ICG-001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. GANT61 attenuated the overexpression of β-catenin and decreased the inhibition of GSK-3β in MCL cells. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β-catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients.

Impact of the COVID-19 Pandemic on the Diagnosis of Malignant Neoplasia of the Bronchus and Lung in the Burgos Region.

To retrospectively analyze the impact of the COVID-19 pandemic on the diagnosis, mortality rate, and survival period of malignant bronchial and lung neoplasms in the Burgos region, with the aim of promoting the development of strategies to improve cancer care management during health crises, highlighting the importance of non-pharmacological approaches to mitigate the negative impacts of future pandemics on lung cancer patients. This retrospective, longitudinal, single-center study was conducted in Burgos from 2019 to 2021. Participants included all patients diagnosed with malignant bronchial and lung neoplasms by the Pneumology unit of Complejo Asistencial Universitario de Burgos during the year immediately before and the year immediately after 31 March 2020, the official start date of the pandemic. Inclusion criteria encompassed patients diagnosed through histological or clinicoradiological methods, who provided informed consent. Data were systematically gathered using a specific template that included demographic information, disease stage, death, and survival time. Statistical analysis involved descriptive methods, ANOVA, and chi-square tests to assess differences in survival time and associations between categorical variables. The results reveal a decrease in the number of patients diagnosed during the pandemic period (154 vs. 105), which could indicate delays in detection. However, there were no significant differences between the two periods, in which more than 60% of cases were detected in stage IV, being incompatible with survival. Although fewer patients died during the pandemic than expected (p = 0.015), patients diagnosed after the onset of the pandemic had a shorter survival time (182.43 ± 142.63 vs. 253.61 ± 224.30; p = 0.038). Specifically, those diagnosed in stage I during the pre-pandemic had a much longer survival time (741.50 days) than the rest of the patients (p < 0.05). In addition, among those diagnosed in stage IV, those diagnosed after the beginning of the pandemic had a shorter survival time (157.29 ± 202.36 vs. 241.18 ± 218.36; p = 0.026). Understanding these changes can support both medical strategies and non-pharmacological therapies to improve cancer care management during health crises, thus contributing to the optimization of public health.

Chromosomal-level genome assembly of Hylurgus ligniperda: insights into host adaptation and environmental tolerance

BackgroundHylurgus ligniperda (Coleoptera: Curculionidae) is a worldwide forest quarantine pest. It is widely distributed, has many host tree species, and possesses strong adaptability. To explore its environmental adaptability and the related molecular mechanisms, we conducted chromosome-level genome sequencing and analyzed the transcriptome under different environmental factors, identifying key expressed genes.ResultsWe employed PacBio, Illumina, and Hi-C sequencing techniques to assemble a 520 Mb chromosomal-level genome of H. ligniperda, obtaining an N50 of 39.97 Mb across 138 scaffolds. A total of 10,765 protein-coding genes were annotated after repeat masking. Fourteen chromosomes were identified, among which Hyli14 was determined to be the sex chromosome. Survival statistics were tested over various growth periods under high temperature and low humidity conditions. The maximum survival period of adults reached 292 days at 25 °C, 65% relative humidity. In comparison, the maximum survival period was 14 days under 35 °C, 65% relative humidity, and 106 days under 25°C, 40% relative humidity. This indicated that environmental stress conditions significantly reduced adults' survival period. We further conducted transcriptome analysis to screen for potentially influential differentially expressed genes, such as CYP450 and Histone. Subsequently, we performed gene family analysis to gain insights into their functions and interactions, such as CYP450 and Histone. CYP450 genes affected the detoxification metabolism of enzymes in the Cytochrome P450 pathway to adapt to different environments. Histone genes are involved in insect hormone biosynthesis and longevity-regulating pathways in H. ligniperda to adapt to environmental stress.ConclusionsThe genome at the chromosome level of H. ligniperda was assembled for the first time. The mortality of H. ligniperda increased significantly at 35 ℃, 65% RH, and 25 ℃, 40% RH. CYP450 and Histone genes played an important role in response to environmental stress. This genome offers a substantial genetic resource for investigating the molecular mechanisms behind beetle invasion and spread.

Trends in Mortality for Anaplastic Thyroid Cancer: Have We Made Progress?

IntroductionAnaplastic thyroid cancer (ATC) has one of the highest mortality rates of all human malignancies, accounting for two-thirds of all thyroid cancer deaths. Despite multimodal treatment, ATC still has a reported median survival period of 6 mo. Recent single-center studies have reported improved survival with the approval of new treatments for ATC. In this study, we sought to investigate whether the approval of new treatments and use of multimodal treatments was associated with reduced risk of mortality over time nationally. MethodsEight hundred and seventy four patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results database that were diagnosed with ATC from 1990 to 2020 were included in this study. Cox proportional hazards models were used to assess the change in 2-y survival over time and to identify characteristics associated with survival. Overall survival (OS) and cancer specific survival (CSS) were both evaluated. ResultsThe OS within 2 y of diagnosis was 14% and the CSS was 19%. For every 3-y increase in diagnosis year from 1990 to 2020, there was no significant change in the CSS (adjusted hazard ratio [95% confidence interval]: 0.98 [0.94, 1.01]). Patients who received treatment (surgery, chemotherapy, and/or radiation) had an increased CSS (adjusted hazard ratio [95% confidence interval]: 0.42 [0.32, 0.55]). ConclusionsWe observed no significant change in OS or CSS after adjusting for confounders by year of diagnosis. Though receiving treatment was associated with increased CSS, more effective treatments are needed in the future to increase survival time in patients with ATC.

Tele-medicine controlled hospital at home is associated with better outcomes than hospital stay.

Hospital-at-home (HAH) is increasingly becoming an alternative for in-hospital stay in selected clinical scenarios. Nevertheless, there is still a question whether HAH could be a viable option for acutely ill patients, otherwise hospitalized in departments of general-internal medicine. This was a retrospective matched study, conducted at a telemedicine controlled HAH department, being part of a tertiary medical center. The objective was to compare clinical outcomes of acutely ill patients (both COVID-19 and non-COVID) admitted to either in-hospital or HAH. Non-COVID patients had one of three acute infectious diseases: urinary tract infections (UTI, either lower or upper), pneumonia, or cellulitis. The analysis involved 159 HAH patients (64 COVID-19 and 95 non-COVID) who were compared to a matched sample of in-hospital patients (192 COVID-19 and 285 non-COVID). The median length-of-hospital stay (LOS) was 2 days shorter in the HAH for both COVID-19 patients (95% CI: 1-3; p = 0.008) and non-COVID patients (95% CI; 1-3; p < 0.001). The readmission rates within 30 days were not significantly different for both COVID-19 patients (Odds Ratio (OR) = 1; 95% CI: 0.49-2.04; p = 1) and non-COVID patients (OR = 0.7; 95% CI; 0.39-1.28; p = 0.25). The differences remained insignificant within one year. The risk of death within 30 days was significantly lower in the HAH group for COVID-19 patients (OR = 0.34; 95% CI: 0.11-0.86; p = 0.018) and non-COVID patients (OR = 0.38; 95% CI: 0.14-0.9; p = 0.019). For one year survival period, the differences were significant for COVID-19 patients (OR = 0.5; 95% CI: 0.31-0.9; p = 0.044) and insignificant for non-COVID patients (OR = 0.63; 95% CI: 0.4-1; p = 0.052). Care for acutely ill patients in the setting of telemedicine-based hospital at home has the potential to reduce hospitalization length without increasing readmission risk and to reduce both 30 days and one-year mortality rates.

Behind Armor Blunt Trauma: Liver Injuries Using a Live Animal Model.

While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current behind armor blunt trauma standard. The purpose of this study was to report on the methods, procedures, and data collected from swine. Live swine tests were conducted after obtaining approvals from the local institution and the Army Care and Use Review Office of the U.S. Department of Defense. Trachea tubes and an intravenous line were introduced before administering anesthesia. Pressure transducers were inserted into the lungs and aorta. An indenter simulating the backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers was used to deliver impact loading to the liver region. A triaxial accelerometer was included in the indenter design. The animals were monitored for 6 hours, necropsies were performed, and injuries were identified. Biomechanical data of the energy, velocity, deflection, viscous criterion, force, and impulse variables were obtained for each test. Peak accelerations, velocities, deflections, forces, impulse, and energies ranged from 897 to 5,808 g, 21 to 59 m/s, 1.96 to 8.87 cm, 2.3 to 13.1 kN, 1.1 to 7.1 Ns, and 58 to 387 J, respectively. The peak viscous criterion ranged from 0.8 to 5.8 m/s. All animals survived the 6-hour survival period. Three animals responded with liver lacerations while the remaining 4 did not have any injuries. The experimental design based on parallel tests with whole body human cadavers and cadaver swine was found to be successful in delivering controlled impacts to the liver region of live swine and reproducing liver injuries. Previously used biomechanical measures as potential candidates for injury criteria development were obtained. Using this proven model, tests with additional samples are needed to develop injury risk curves for liver impacts and obtain regional (liver) injury criteria.

Craniospinal irradiation for leptomeningeal metastasis of solid tumors: survival analysis and prognostic factors.

We conducted a study to examine the treatment outcomes and prognostic factors for patients who underwent craniospinal irradiation (CSI) for leptomeningeal metastasis of solid tumors. This retrospective study included patients who received CSI for leptomeningeal metastasis at a single institute between 2010 and 2021. Data from clinical records and the radiation information system were obtained and analyzed. A total of 25 patients were included in the study. Eighteen patients (72%) completed the scheduled CSI. The median overall survival (OS) period was 4.8months (95% confidence interval (CI): 3.2-10.0months). Symptom relief was achieved in four out of 23 symptomatic patients (17%). Non-hematological adverse events occurred in 12 patients (48%), with 1 patient (4%) developing Grade 3 bacterial meningitis and the other patients having Grade 1-2 events. Twenty patients (80%) had hematological adverse events of Grade 3 or higher. Grade 4 hematologic toxicities occurred in 3 patients (12%) due to neutropenia and in 11 patients (44%) due to lymphopenia. In multivariate Cox regression analysis, the systemic immune-inflammation index (SII) was identified as the only significant parameter for predicting OS. The median OS periods for patients with SII < 607 and SII ≥ 607 were 6.1 and 2.1months, respectively (P = 0.003). In conclusion, this study showed the treatment outcomes of CSI for leptomeningeal metastasis of solid tumors. It was shown that a high baseline SII was associated with shorter OS after CSI. The findings will contribute to the evaluation of prognosis after CSI.

Identification of an autophagy- and macropinocytosis-related prognostic signature for the prediction of prognosis and therapeutic response in gastric cancer.

Traditional liquid biopsy markers show a low rate of positivity and accurate in gastric cancer. With the rapid advancement of sequencing technology, scientists have identified promising research avenues in this field. Autophagy and macropinocytosis utilize diverse pathways and mechanisms to supply resources and fuel for tumor growth. Nonetheless, their potential interplay introduces an untapped avenue for the discovery of novel tumor biomarkers. To develop an innovative prognostic signature based on autophagy- and micropinocytosis-related genes, with the aim to predict the outcome and therapeutic response of gastric cancer patients. Additionally, to validate the prognostic impact of this signature, and elucidate the role of representative molecules in gastric cancer. To construct and validate a prognostic signature for gastric cancer, bioinformatics methods such as COX regression, LASSO regression, survival analysis, ROC curve, and nomogram were utilized based on the sequencing and clinical data of gastric cancer patients retrieved from the TCGA and GEO databases. GSEA functional enrichment analyses were employed to predict the biological functions. Meanwhile, qRT-PCR and Western blot experiments were utilized to quantify the mRNA and protein expression levels. Furthermore, the EdU assay and colony formation assay were utilized to examine the cell proliferation ability while the Transwell assays were conducted to assess the migration and invasion abilities of gastric cancer cells. Through consistency clustering and univariate COX analyses, potential prognostic genes involved in both autophagy and macropinocytosis were identified. Based on these genes, a 9-gene signature was constructed, which demonstrated high accuracy in predicting gastric cancer patients' survival period, immunotherapeutic response, and chemotherapy drug tolerance. Furthermore, qRT-PCR analyses of gastric cancer tissue samples showed that the representative genes of this signature were aberrantly overexpressed in gastric cancer, with MATN3, as the most notable molecule, exhibiting significant carcinogenic effects on cancer cells by actively regulating their proliferation, migration, and invasion abilities. Our newly created prognostic signature possesses significant potential as a biomarker for gastric cancer, while MATN3 is identified as an oncogenic factor in gastric cancer. This brings to light new perspectives, which can contribute to enhancing the diagnosis and treatment of gastric cancer.

Giant mucinous liposarcoma of the abdominal cavity: A case report.

Mucinous liposarcoma myxoid liposarcoma is a malignant mucoid soft tissue tumor derived from undifferentiated stromal cells in perivascular, subbody cavity and intermuscular space, and composed of cells at different stages of differentiation from preadipocytes to mature cells. In rare cases, it may change from lipoma malignancy. The main manifestations is painless mass, relatively slow growth, the course can last decades, the prevalence of liposarcoma in the population is 14% to 18%, mainly in adults, male prevalence is higher than women, but not significant. The main good hair part is the thigh, have mucinous sex, high differentiation type, dedifferentiation type, polymorphic type. Clinical diagnosis is difficult, and there are no obvious symptoms in the early stage, so the diagnosis should be combined with B ultrasound, MRI, CT, and other auxiliary examinations. The gold standard is pathological examination. In December 2023, our department admitted a patient with a mucinous abdominal mass. The report is as follows. Does liposarcoma metastasize? Is any chemotherapy required after surgery? Will it ever relapse in the future? What is the survival period after surgery? Mucinous liposarcoma. Surgical resection of the sarcoma. The nodule sample was 33 * 28 * 13 cm, with complete capsule, gray and yellow sections, fine texture, soft, gray, red, grayish, and yellow mucoid nodules in some areas, and the maximum diameter of the nodules was 21cm. Immunohistochemistry was: CD34 (+), CDK 4 (+), CK (-), Desmin (weak +), Ki67 (index 5%), MDM 2 (-), p16 (weak +), S-100P (+), Vimentin (+), BCL-2 (+). He was also sent to the Department of Pathology of Peking Union Medical College Hospital for consultation with Professor Lu Zhaohui, whose consultation opinion was in line with myxoliposarcoma. Retroperitoneal liposarcoma is a common retroperitoneal tumor, but it is relatively rare in clinical practice; the overall morbidity is low, mainly manifested as abdominal pain and abdominal distension, abdominal distension, and a long course of disease; it is not sensitive to radiotherapy and chemotherapy, and should be closely follow up by CT examination to understand the recurrence and metastasis.

Cutaneous Melanoma: An Overview of Physiological and Therapeutic Aspects and Biotechnological Use of Serine Protease Inhibitors.

Metastatic melanoma stands out as the most lethal form of skin cancer because of its high propensity to spread and its remarkable resistance to treatment methods. In this review article, we address the incidence of melanoma worldwide and its staging phases. We thoroughly investigate the different melanomas and their associated risk factors. In addition, we underscore the principal therapeutic goals and pharmacological methods that are currently used in the treatment of melanoma. The implementation of targeted therapies has contributed to improving the approach to patients. However, because of the emergence of resistance early in treatment, overall survival and progression-free periods continue to be limited. We provide new insights into plant serine protease inhibitor therapeutics, supporting high-throughput drug screening soon, and seeking a complementary approach to explain crucial mechanisms associated with melanoma.

Outcomes of sutured scleral-fixated intraocular lens implantation combined with penetrating keratoplasty

BackgroundThe purpose of the study was to assess visual outcomes, complications, intraocular lens (IOL) stability, and corneal status after sutured scleral-fixated intraocular lens implantation combined with penetrating keratoplasty (PKP).MethodsThis retrospective single-arm cohort study included patients who underwent PKP and sutured scleral-fixated intraocular lens implantation between 2013 and 2018 at the Dhahran Eye Specialty Hospital. The eyes were examined postoperatively at 1, 3, 6, 12, and 24 months. Corneal status, complications, and IOL status were also evaluated periodically, and the number of eyes with a BCVA of > 20/200 was recorded.ResultsTwenty-two eyes from 22 patients were included. The median duration of follow-up was 3 (IQR 1.8; 4.4) years. Reasons for surgery were traumatic globe rupture (six eyes, 27.3%), bullous keratopathy (nine eyes, 40.1%), failed previous graft (five eyes, 22.7%), and corneal scarring (two eyes, 9.1%). Twelve (54.5%) eyes showed a BCVA of > 20/200 (non-blind) at 12 months after surgery and only five (22.7%) before surgery. Twelve months after surgery, 13 patients showed an improvement in BCVA in two lines (59.1%), seven remained the same (31.8%), and 2 deteriorated (9.1%). The indication for surgery (p = 0.2) and the stability of the sutured-scleral fixated IOL (p = 0.8) were not associated with an improvement in BCVA at the final follow-up. The corneal graft remained clear in nine eyes (40.9%) at a median duration of 3 years. The overall average survival period for all corneal grafts was 42.9 months.ConclusionsThe combination of sutured scleral-fixated intraocular lens implants and PKP is an effective intervention for preserving visual acuity in patients with complex cases. However, the risk of graft failure and then need for repeat transplantation should be taken into consideration.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol treatment inhibits abnormal tumor growth by regulating neutrophil infiltration in a non-small cell lung carcinoma mouse model

Excessive neutrophil infiltration into the tumor microenvironment (TME) is an important factor that contributes to tumor overgrowth and limited immunotherapy efficacy. Neutrophils activate various receptors involved in tumor progression, while suppressing the infiltration and activity of cytotoxic T cells and creating optimal conditions for tumor growth. Therefore, the appropriate control of neutrophil infiltration is an effective strategy for tumor treatment.In the present study, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) inhibited tumor overgrowth by suppressing excessive neutrophil infiltration, resulting in >74.97 % reduction in tumor size in a Lewis lung carcinoma (LLC-1) mouse model. All subjects in the positive control group died during the 90-day survival period, whereas only four subjects in the PLAG treatment group survived. PLAG had a significantly higher tumor growth inhibitory effect and survival rate than other neutrophil infiltration-targeting inhibitors (e.g., Navarixin, lymphocyte antigen 6 complex locus G6D antibody [aLy6G]). The ability of PLAG to regulate neutrophil infiltration and inhibit tumor growth depends on thioredoxin-interacting protein (TXNIP). In tumors lacking TXNIP expression, PLAG failed to control neutrophil infiltration and infiltration-related factor release, and the inhibitory effect of PLAG on tumor growth was reduced. PLAG-mediated inhibition of neutrophil infiltration enhances the efficacy of immune checkpoint inhibitors (ICIs), increasing the antitumor efficacy and survival rate by 30 %.In conclusion, PLAG could be a novel alternative to anti-tumor drugs that effectively targets excessive neutrophil infiltration into cancer tissues.

Potential for boron neutron capture therapy (BNCT) with ASCT2-targeted boron agents.

233 Background: Boron Neutron Capture Therapy (BNCT) is a cutting-edge particle irradiation technique that utilizes the nuclear reaction triggered by the irradiation of non-radioactive boron-10 with thermal neutrons, selectively annihilating tumor cells that have incorporated boron. In the clinical arena, Boronophenylalanine (BPA), a phenylalanine compound targeting amino acid receptors, has been the cornerstone of BNCT. While BNCT has been effective against malignant gliomas, its dependency on BPA uptake has illuminated the existence of inherent resistance within specific cells, tissues, and cancer types. This study pivots towards the Alanine-serine-cysteine transporter 2 (ASCT2)—a transporter distinct from LAT1—investigating its potential as a gateway for the development of innovative boron carriers, with the aim of expanding the clinical applicability and effectiveness of BNCT. Methods: This research embarked on in vitro investigations to evaluate boron accumulation in F98 and C6 rat glioma cells, and 9L rat gliosarcoma, following 24 hours of exposure to BPA and GluB-2 (10 μg B/ml each). Complementary in vivo studies involved the intravenous administration of these compounds to an F98 rat brain tumor model, with the subsequent measurement of boron distribution at 2.5, 6, and 24 hours post-administration. The efficacy of these treatments was then ascertained through neutron irradiation experiments, gauging therapeutic outcomes via the survival periods of the subjects. Results: In vitro findings highlighted that GluB-2 facilitated a significantly higher intracellular boron concentration compared to BPA in F98 cells (p=0.02, Student's t-test). In vivo results indicated that the apex of boron biodistribution in tumors was achieved at 2.5 hours post-BPA treatment and at 6 hours post-GluB-2 treatment, with GluB-2 securing a superior maximum intratumor boron concentration. Survival analysis revealed a mean survival of 28.0±2.5 days for the neutron alone group, 37.7±5.0 days for the group receiving BPA IV + BNCT at 2.5 hours, 55.1±19.9 days for the group treated with GluB-2 IV + BNCT at 6 hours, and 25.3±1.4 days for the untreated group. Remarkably, the group treated with GluB-2 demonstrated significantly prolonged survival compared to the BPA-treated group (p&lt;0.001, log-rank test). Conclusions: Combining BNCT with GluB-2 showed superior efficacy over BPA. Further research is needed to optimize boron concentration timing and ASCT2 expression levels, yet GluB-2 presents a promising advancement in BNCT, potentially transforming malignant brain tumor treatment.

Naringin and chloroquine combination mitigates chloroquine-resistant parasite-induced malaria pathogenesis by attenuating the inflammatory response

BackgroundMalaria, characterised by inflammation and multi-organ complications, needs novel chemotherapeutics due to the rise of drug-resistant malaria parasites, which is a serious health issue. Naringin (NGN), a flavanone glycoside (naringenin 7-O-neohesperidose), has a broad spectrum of pharmacological activities but its effect against malaria, alone and in combination, was not deeply investigated. PurposeTo assess the pharmacological efficacy of NGN alone and in combination with chloroquine (CQ) against a Plasmodium strain resistant to CQ and to elucidate its potential mode of action. MethodsThe anti-inflammatory potential of NGN was assessed in mouse microglial cells stimulated with hemozoin by analyzing inflammatory cytokines production. The anti-plasmodial potential of NGN was subsequently tested alone and in combination with CQ against the K1 strain of Plasmodium using the fixed ratio combination method. Further, we evaluated NGN's antimalarial efficacy against the CQ-resistant Plasmodium yoelii nigeriensis N67 strain (P. yoelii), both alone and in combination with CQ, by measuring parasitemia and survival rates. To comprehend the impact of NGN on malaria-induced inflammation in mice, we measured pro-inflammatory cytokines elevated by activated NF-кB signalling. These findings were supported by mRNA and immunohistochemical analyses of malaria-infected mice's liver and brain tissues. ResultsOur study demonstrated that NGN displayed anti-plasmodial activity, which was further augmented when combined with CQ. At 50 µM, NGN significantly reduced the elevation of pro-inflammatory cytokines in synthetic hemozoin-stimulated microglial cells. Compared to P. yoelii-infected mice, NGN (12.5 mg kg-1) significantly reduced parasitemia in mice, resulting in a survival period of up to 13 days. Survival improved by up to 20 days when NGN and CQ were given in combination. NGN, as revealed by immunohistochemical examination of brain and liver tissues, interfered with the NF-кB pathway, potentially reducing the elevation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-18, IFN-γ, and IL-6). This was supported by the overexpression of inflammation-regulatory genes (TGFβ, Nrf2, HO-1, and iNOS) and the downregulation of inflammation-stimulating genes (NF-κB, NLRP3, and caspase-1). Histopathological analysis demonstrated the potential of NGN to restore liver and brain tissues to normal. The substantial decrease in the expression and production of ICAM-1 protein in the brain tissue implies the beneficial effects of NGN, pointing towards its potential for mitigating brain pathology. ConclusionThe findings of this study revealed NGN as a promising drug-like candidate for the management of CQ-resistant parasite-induced malaria pathogenesis for adjunctive therapy in combination with standard antimalarial drugs through its modulation of the NF-κB-mediated inflammation.