Search Results (39)

Background/Objectives: Although the binarism between type I and II endometrial cancer was dismissed and substituted with molecular classification, histopathological features remain of paramount importance. Hence, analysing survival outcomes according to histological type, our aim is to clarify whether the morphological features of the tumour retain prognostic relevance in the context of advanced disease. Methods: This is a retrospective analysis led within the Thames Valley Cancer Alliance Network. Results: We include 148 FIGO 2009 stage III–IV patients affected by endometrioid endometrial cancer (EEC) G1, G2, and G3, carcinosarcoma (CS), serous carcinoma (SC), and clear cell carcinoma (CCC) of the uterus. Five year overall survival (OS) is distinct among the histological groups (p-value < 0.001), being 73.3% for G2 endometrioid, 49.2% for G3 endometrioid, 8.3% for CS, and 28.4% for SC. The divergence was marked also for 5 year progression-free survival (PFS) (p-value < 0.001) as follows: for G2 endometrioid, was 76.4%; for G3 endometrioid, 52.7%; and for carcinosarcoma, 5.9%. PFS after 18 months for serous carcinoma was 5.7%. The multivariate analysis found G3 endometrioid (HR 2.91, 95% CI 1.20–7.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07–29.11, p-value < 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16–10.83, p-value < 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10–3.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28–41.11) and serous carcinoma (HR 17.68, 95% CI 6.41–48.75) were associated with an increased risk of recurrence. Conclusions: Our findings testify that, beyond the disease stage, histological subtype remains a major determinant of survival outcome. Cervical involvement is associated with a more aggressive disease, possibly correlated to death beyond relapse. Prospective trials involving advanced stage endometrial cancer, stratified by histological subtype and integrated with the molecular classification, are required. Full article

Background: Limited real-world data (RWD) may provide important information regarding diagnostic and treatment patterns in patients (pts) with AL Amyloidosis. The aim was to analyze the characteristics, treatment approach and clinical outcome of patients in the real-world settings. Materials and Methods: RWD of 60 pts diagnosed with AL amyloidosis were analyzed. Advanced cardiac involvement, Mayo Clinical Stage (CS) IIIa and IIIb, and Revised-Mayo CS III and IV, has been found in 26.7%, and 16.7%, or 33.3% and 16.7%, respectively. Bortezomib (Bz)-based regimens were applied in 36 pts (60%), and alkylating-based regimens in 24 pts (40%). In 8 pts (13.3%) treated initially with CyBorD induction, high-dose therapy with Melphalan and autologous stem cell transplantation (HDT + ASCT) was applied as the first line of treatment. Results: The overall response rate (ORR, ≥partial response) was achieved in 40 pts (70%). Patients treated with Bz-based induction followed by HDT + ASCT achieved significantly better hematologic (p = 0.001), cardiac (p = 0.004) and renal response rates (p = 0.002) in comparison to CyBorD or Alk-based regimens alone. There was no difference in PFS between those groups (p = 0.733), but patients treated with CyBorD + HDT + ASCT had significantly durable OS (p = 0.039). Univariate analysis pointed out the predictive influence of cardiac involvement (Mayo CS and Revised Mayo CS), ASCT eligibility, and hematologic, cardiac, renal and composite response rates. Conclusions: Advanced cardiac involvement and cardiac and hematologic response still retain adverse prognostic impact on the clinical outcome. Bz-based combinations significantly improved the survival of patients with AL amyloidosis, regardless of HDT + ASCT treatment. Full article

In addition to being governed by genetic factors, environmental factors also play a crucial role in influencing the fragrance of rice. In this research, the high-quality rice variety Dalixiang was selected as the experimental material to investigate the impacts of soil nutrients in Guiyang and Meitan on its fragrance. The results indicated that the levels of ammonium nitrogen, organic matter, total nitrogen, available nitrogen, and the pH value in the soil of Meitan were lower compared to those in Guiyang. Conversely, the contents of total potassium, available phosphorus, and available potassium were higher in Meitan. Specifically, the concentrations of 2-acetyl-1-pyrroline (2AP) in the leaves of Dalixiang at the heading stage and in the grains at the maturity stage at the Meitan planting site were 0.13 mg/kg and 0.56 mg/kg, respectively. These values were significantly lower than the 0.17 mg/kg and 0.64 mg/kg measured at the Guiyang planting site. This phenomenon is associated with the higher expression levels of the betaine aldehyde dehydrogenase (OsBadh2) gene, enhanced enzyme activities, and a greater content of γ-aminobutyric acid (GABA) in the leaves of Dalixiang at the Meitan planting site. In contrast, the expression levels of genes related to triose phosphate isomerase (OsTPI), proline dehydrogenase (OsProDH), ornithine aminotransferase (OsOAT), and Delta1-pyrroline-5-carboxylic acid synthetase (OsP5CS), along with their corresponding enzyme activities, as well as the contents of methylglyoxal, proline, and ornithine, were lower. In conclusion, due to the influence of the Guiyang environment, the biosynthesis of Dalixiang 2AP was promoted, which made the Dalixiang planted in Guiyang stronger than that planted in Meitan. This study provides a theoretical basis for the selection of the best planting area of Dalixiang and the improvement of Dalixiang flavor through agronomic cultivation techniques. Full article

TRPV1 regulates neuronal and vascular function mediated by NO and CGRP. Systemic arterial hypertension (SAH) induces an imbalance in vascular mediators NO and CGRP by altering the transport of Ca²⁺ ions through TRPV1, generating cellular damage. We studied the effect of topical capsaicin (CS) treatment on cardiac mechanical work, oxidative stress (TAC, NO, BH4, and BH2), cellular damage (MDA, MTO, and 8HO2dG), and inflammation (IL-6 and TNFα), generated by SAH, which was induced by L-NAME, in male Wistar rats. CS was added to a moisturizing cream and applied to the abdomen of animals for two weeks. Experimental groups were as follows: (1) Control, (2) Control+Cream, (3) Hypertensive, and (4) Hypertensive+Cream. Hearts were exposed to ischemia-reperfusion (I-R) using the Langendorff technique to study the potential cardioprotection of CS. Expression of SOD1, SOD2, catalase, eNOS, pNOS, TRPV1, and CGRP in cardiac tissue was evaluated. In the Hypertensive group, TRPV1 activation by CS (Hypertensive+Cream) reduced oxidative stress (OS), decreasing cellular damage and inflammation and increasing TAC, modulating biochemical and tissue alterations induced by OS generated by SAH. In parallel, an increase in tissue levels and the expression of CGRP, TRPV1, and eNOS, induced by CS, was observed. These findings indicate that pretreatment with CS attenuates cardiac I-R and SAH injury in rats. The cardioprotective mechanism may be based on TRPV1-mediated CGRP overexpression. Full article

Background/Objectives: Bowel resection may be necessary during cytoreductive surgery (CS) in advanced epithelial ovarian cancer to achieve complete tumor removal. However, concerns about increased perioperative risks and unclear survival benefits have led to ongoing debate. This study aimed to evaluate the impact of bowel resection on perioperative mortality and overall survival (OS) in patients undergoing CS. Methods: We retrospectively reviewed 127 patients with FIGO stage IIB–IV epithelial ovarian cancer who underwent primary or interval CS between 2007 and 2021. Patients were stratified based on the performance of bowel resection. Clinical, surgical, and survival data were analyzed using Kaplan–Meier survival analysis and Cox proportional hazards modeling. Primary outcomes were 90-day mortality and OS. Results: Bowel resection was performed in 58 patients (46%) with more extensive disease and poorer ECOG performance scores. Although the resection group had increased perioperative risks (e.g., higher transfusion rates and ICU use), OS was similar between groups (log-rank p = 0.122). Multivariate analysis identified that increasing age (HR = 1.042, p = 0.005) was independently associated with poorer OS, whereas lymph node dissection (HR = 0.450, p = 0.003) and undergoing primary CS (HR = 0.540, p = 0.047) were associated with improved survival. Bowel resection was not independently associated with OS. Conclusions: Bowel resection does not adversely affect OS when optimal cytoreduction is achieved. Although it increases perioperative complexity, it can be safely incorporated into CS in selected patients. These findings support its use as part of an individualized surgical strategy for advanced ovarian cancer. Full article

Objective: Mental fatigue (MF) induced by prolonged cognitive tasks poses significant risks to postural stability, yet its effects on multi-sensory integration remain poorly understood. Method: This study investigated how MF alters sensory reweighting and postural control in 27 healthy young males. A 45 min incongruent Stroop task was employed to induce MF, validated via subjective Visual Analog Scale (VAS) scores and psychomotor vigilance tests. Postural stability was assessed under four sensory perturbation conditions (O-H: no interference; C-H: visual occlusion; O-S: proprioceptive perturbation; C-S: combined perturbations) using a Kistler force platform. Center of pressure (COP) signals were analyzed through time-domain metrics, sample entropy (SampEn), and Discrete Wavelet Transform (DWT) to quantify energy distributions across sensory-related frequency bands (visual: 0–0.1 Hz; vestibular: 0.1–0.39 Hz; cerebellar: 0.39–1.56 Hz; proprioceptive: 1.56–6.25 Hz). Results: MF significantly reduced proprioceptive energy contributions (p < 0.05) while increasing vestibular reliance under O-S conditions (p < 0.05). Time-domain metrics showed no significant changes in COP velocity or displacement, but SampEn decreased under closed-eye conditions (p < 0.001), indicating reduced postural adaptability. DWT analysis highlighted MF’s interaction with visual occlusion, altering cerebellar and proprioceptive energy dynamics (p < 0.01). Conclusion: These findings demonstrate that MF disrupts proprioceptive integration, prompting compensatory shifts toward vestibular and cerebellar inputs. The integration of nonlinear entropy and frequency-domain analyses advances methodological frameworks for fatigue research, offering insights into real-time sensor-based fatigue monitoring and balance rehabilitation strategies. This study underscores the hierarchical interplay of sensory systems under cognitive load and provides empirical evidence for optimizing interventions in high-risk occupational and clinical settings. Full article

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and neuroinflammation, often accompanied by cognitive impairment. This study aims (1) to investigate the potential of glatiramer acetate (GA) as a therapy for preventing cognitive decline in patients with MS (pwMS) by modulating oxidative stress (OS) and (2) to seek out the differences in cognition between pwMS in a cohort exhibiting good clinical evolution and control subjects (CS). An exploratory, prospective, multicentre, cross-sectional case–control study was conducted, involving three groups at a 1:1:1 ratio—41 GA-treated pwMS, 42 untreated pwMS, and 42 CS. The participants performed a neuropsychological battery and underwent venepuncture for blood sampling. The inclusion criteria required an Expanded Disability Status Scale score of ≤3.0 and a minimum of 5 years of MS disease. Concerning cognition, the CS had a better performance than the pwMS (p = <0.0001), and between those treated and untreated with GA, no statistically significant differences were found. Regarding oxidation, no statistically significant differences were detected. Upon categorizing the pwMS into cognitively impaired and cognitively preserved groups, the lactate was elevated in the pwMS with cognitive preservation (p = 0.038). The pwMS exhibited a worse cognitive performance than the CS. The pwMS treated with GA did not show an improvement in oxidation. Lactate emerged as a potential biomarker for cognitive preservation. Full article

Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We aimed to test if high parenteral (200 mg/kg/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (n = 75) and interventional Group B (n = 75). Group B intraoperatively received one-fourth (i.e., 50 mg/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke’s score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%, p < 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3, p < 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results. Full article

The most important volatile in determining the aroma of fragrant rice is 2-Acetyl-1-pyrroline (2-AP); however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by the genetic transformation of the Indica rice cultivar, i.e., ‘Zhonghua11′, which knocks out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the OsbZIP60-like transcription factor was screened by yeast one-hybrid assays. The OsbZIP60-like transcription factor specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that the OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, OsP5CS1 gene expression was significantly down-regulated in the Osbzip60-like mutant and resulted in a substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased, whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of the OsbZIP transcription factor in fragrant rice. Full article

Exogenous or endogenous caffeine application confers resistance to diverse biotic stresses in plants. In this study, we demonstrate that endogenous caffeine in caffeine-producing rice (CPR) increases tolerance even to abiotic stresses such as water deficit. Caffeine produced by CPR plants influences the cytosolic Ca²⁺ ion concentration gradient. We focused on examining the expression of Ca²⁺-dependent protein kinase genes, a subset of the numerous proteins engaged in abiotic stress signaling. Under normal conditions, CPR plants exhibited increased expressions of seven OsCPKs (OsCPK10, OsCPK12, OsCPK21, OsCPK25, OsCPK26, OsCPK30, and OsCPK31) and biochemical modifications, including antioxidant enzyme (superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase) activity and non-enzymatic antioxidant (ascorbic acid) content. CPR plants exhibited more pronounced gene expression changes and biochemical alterations in response to water-deficit stress. CPR plants revealed increased expressions of 16 OsCPKs (OsCPK1, OsCPK2, OsCPK3, OsCPK4, OsCPK5, OsCPK6, OsCPK9, OsCPK10, OsCPK11, OsCPK12, OsCPK14, OsCPK16, OsCPK18, OsCPK22, OsCPK24, and OsCPK25) and 8 genes (OsbZIP72, OsLEA25, OsNHX1, OsRab16d, OsDREB2B, OsNAC45, OsP5CS, and OsRSUS1) encoding factors related to abiotic stress tolerance. The activity of antioxidant enzymes increased, and non-enzymatic antioxidants accumulated. In addition, a decrease in reactive oxygen species, an accumulation of malondialdehyde, and physiological alterations such as the inhibition of chlorophyll degradation and the protection of photosynthetic machinery were observed. Our results suggest that caffeine is a natural chemical that increases the potential ability of rice to cope with water-deficit stress and provides robust resistance by activating a rapid and comprehensive resistance mechanism in the case of water-deficit stress. The discovery, furthermore, presents a new approach for enhancing crop tolerance to abiotic stress, including water deficit, via the utilization of a specific natural agent. Full article

Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with either SIRT or CS-PHP. We included 62 patients with hepatic metastasized uveal melanoma (n = 34 with SIRT, receiving 41 cycles; n = 28 with CS-PHP, receiving 56 cycles) that received their treatments between 12/2013 and 02/2020 at a single center. We evaluated their response according to the RECIST 1.1, as well as progression-free survival (PFS) and overall survival (OS), after the initiation of the first cycle of the liver-directed treatment using Cox regression, adjusted via propensity score analysis for confounders, including the amount of hepatic involvement. The disease control rate was 18% for SIRT and 30% for CS-PHP. The median (range) of PFS was 127.5 (19–1912) days for SIRT and 408.5 (3–1809) days for CS-PHP; adjusted Cox regression showed no significant difference (p = 0.090). The median (range) of OS was 300.5 (19–1912) days for SIRT and 516 (5–1836) days for CS-PHP; adjusted Cox regression showed a significant difference (p = 0.006). In our patient cohort, patients treated with CS-PHP showed a significantly longer OS than patients treated with SIRT. CS-PHP might therefore be preferable for patients with liver-dominant metastatic uveal melanoma. Full article

Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. Methods: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. Results: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. Conclusion: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required. Full article

(1) Background: Sarcopenia lasting >1 year might be considered a chronic condition in many HNSCC patients. CT-scan-derived Skeletal Muscle Mass Index (SMI) is an established surrogate of sarcopenia; yet, the cut-off reported in the literature (literature-based, lb-SMI < 43.2) is mainly based on the risk of chemoradiotherapy-induced toxicity, and the optimal value to discriminate OS is under-investigated. (2) Methods: The effect on OS of the lb-SMI cutoff was compared with an untailored OS-oriented SMI cutoff obtained in a cohort of consecutive advanced HNSCC patients treated with primary chemoradiotherapy, bio-chemotherapy or chemo-immunotherapy (cohort-specific, cs-SMI cutoff). Gender- and BMI-tailored (gt-SMI and bt-SMI) cut-offs were also evaluated. Cutoff values were identified by using the maximally selected rank statistics for OS. (3) Results: In 115 HNSCC patients, the cs-SMI cutoff was 31.50, which was lower compared to the lb-SMI reported cut-off. The optimal cut-off separately determined in females, males, overweight and non-overweight patients were 46.02, 34.37, 27.32 and 34.73, respectively. gt-SMI categorization had the highest effect on survival (p < 0.0001); its prognostic value was independent of the treatment setting or the primary location and was retained in a multivariate cox-regression analysis for OS including other HNSCC-specific prognostic factors (p = 0.0004). (4) Conclusions: A tailored SMI assessment would improve clinical management of sarcopenia in chemoradiotherapy-, bio-chemotherapy- or chemo-immunotherapy-treated HNSCC patients. Gender-based SMI could be used for prognostication in HNSCC patients. Full article

As a great threat to the normal growth of rice, drought not only restricts the growth of rice, but also affects its yield. Glutathione S-transferases (GSTs) have antioxidant and detoxification functions. In rice, GSTs can not only effectively cope with biological stress, but also play a defense role against abiotic stress. In this study, we selected OsGSTU17, a member gene that was induced by drought, to explore the role of GSTs and analyze their physiological mechanisms that are involved in rice drought tolerance. With the CRISPR/Cas9 knockout system techniques, we obtained two independent mutant lines of osgstu17. After 14 days of drought stress treatment, and then re-supply of the water for 10 days, the survival rate of the osgstu17 mutant lines was significantly reduced compared to the wild-type (WT). Similarly, with the 10% (w/v) PEG6000 hydroponics experiment at the seedling stage, we also found that compared with the WT, the shoot and root biomass of osgstu17 mutant lines decreased significantly. In addition, both the content of the MDA and H₂O₂, which are toxic to plants, increased in the osgtu17 mutant lines. On the other hand, chlorophyll and proline decreased by about 20%. The activity of catalase and superoxide dismutase, which react with peroxides, also decreased by about 20%. Under drought conditions, compared with the WT, the expressions of the drought stress-related genes OsNAC10, OsDREB2A, OsAP37, OsP5CS1, OsRAB16C, OsPOX1, OsCATA, and OsCATB in the osgtu17 mutant lines were significantly decreased. Finally, we concluded that knocking out OsGSTU17 significantly reduced the drought tolerance of rice; OsGSTU17 could be used as a candidate gene for rice drought-tolerant cultivation. However, the molecular mechanism of OsGSTU17 involved in rice drought resistance needs to be further studied. Full article

(1) Background: We aim to find a novel blink parameter in nasolacrimal duct obstruction (NDO) patients and analyze parameters that could reflect subjective symptoms and objective indicators at the same time through a blink dynamic analysis. (2) Methods A retrospective study was conducted with 34 patients (48 eyes) who underwent lacrimal passage intubation (LPI) and 24 control groups (48 eyes). All patients’ blink patterns were measured using an ocular surface interferometer before and after LPI, including total blink (TB) and partial blink (PB) and the blink indices blink time (BT), lid closing time (LCT), closure time (CT), lid opening time (LOT), interblink time (IBT), closing speed (CS) and opening speed (OS). The tear meniscus height (TMH) was measured, and the questionnaire “Epiphora Patient’s Quality of Life (E-QOL),” which includes daily activity restriction as well as static and dynamic activities, was completed. (3) Results: Compared to CT and the ratio of CT during BT (CT/BT) in control (89.4 ± 20.0 msec, 13.16%), those in NDOs were longer (140.3 ± 92.0 msec, 20.20%) and were also related to TMH. After LPI, CT and CT/BT were recovered to 85.4 ± 22.07 msec, 13.29% (p < 0.001). CT and CT/BT showed a positive correlation with the E-QOL questionnaire score, particularly with dynamic activities. (4) Conclusions: CT and CT/BT, which are objective indicators associated with subjective symptoms of patients, are considered new blink indices for the evaluation of NDO patients with Munk’s score. Full article