Early Stages Of Treatment Research Articles

The Experience of Patients with Endocrine Therapy for Breast Cancer: A Patient Journey Map Based on Qualitative Research.

(1) Background: While there is extensive documentation on the medical experience of breast cancer, a thorough understanding of the various stages of endocrine therapy remains insufficient. The aim of this study was to map the experiences and coping styles of breast cancer patients during endocrine therapy. (2) Methods: Qualitative research was conducted to gather insights into the experiences of breast cancer patients undergoing endocrine therapy. The themes were organized through content analysis and induction. Subsequently, patients were invited for face-to-face interviews at a top-three hospital in Guangzhou to supplement and validate the findings from the literature review. The patient journey was then mapped based on both the literature review and the semi-structured interviews. (3) Results: A total of 24 studies were included that described patients' experiences and behaviors during the early, middle, and late stages of treatment, leading to the formation of a preliminary framework. Interviews were conducted with 20 patients, which confirmed and enriched the findings from the literature review. Based on these results, a stage trajectory for endocrine therapy in breast cancer was established. (4) Conclusions: The patient journey map developed in this study clearly and intuitively illustrates the thought and emotion matrix, as well as the behavior matrix, of breast cancer patients undergoing endocrine therapy. This provides a theoretical foundation for enhancing clinical services tailored to the needs of these patients.

"Moral spaces": A feasibility study to build nurses' ethical confidence and competence.

Background: Pre-licensure ethics nursing education does not adequately prepare and instill confidence in nurses to address ethical issues, and yet ethics education provides nurses with greater confidence to take moral action, which can mitigate the negative effects of moral distress. Objectives: To assess the feasibility and acceptability of a nursing ethics education program that included simulated case-based ethics competencies as a form of evaluation. The program aimed at building nurses' ethical knowledge and confidence to respond to ethical challenges in practice. Research design: A prospective, longitudinal, correlational, single-cohort feasibility study using an investigator-developed survey and intervention field data. Participants and research context: Registered nurses were recruited from an academic quaternary-care medical center and 9 small- to mid-sized regional hospitals within one health system in the Midwest United States. Ethical considerations: IRB approval was obtained. Participants could complete the educational program regardless of research process participation. Findings: Of 20 participants, 19 (95%) provided post-program surveys and 18 completed competencies. Median (IQR) scores with quartiles for scheduling, timing, and length of sessions were all 10.0 [9.0, 10.0], and participants perceived that the content was interesting, increased knowledge and confidence in ethics, increased skills in providing ethical care, and would recommend the program to colleagues. Of factors, an increase in ethics knowledge had the highest "always agree" (17, 89.5%) response. Most participants reported that ethics competencies were appropriate 9.0 [9.0, 10.0] and sufficiently challenging 10.0 [9.0, 10.0]. Discussion: The education program developed nurses' ethics knowledge and confidence. The single-cohort feasibility design provided early-stage intervention outcomes; however, a larger randomized controlled trial would substantiate program value. Conclusion: This novel ethics education program was highly feasible and acceptable to hospital-based nurses who reported increased knowledge and confidence in providing ethical care. Simulated case-based ethics competencies were an appropriate evaluation method.

Nuvance Health/Vassar Brothers Medical Center, Poughkeepsie, NY

Introduction: Mycosis fungoides (MF) is a form of cutaneous T cell non-Hodgkin’s lymphoma that presents as patches in early stages of the disease that can progress into thick plaques and eventually leukemia in later stages. Treatments currently focus on symptom repertoire, as well as disease stage. However, patch stage MF has been shown to be more responsive to phototherapy than plaque stage MF. This report aims to expand the literature regarding the efficacy and safety of early-stage MF treatment with 308-nm excimer lamp. Case Report: A 55-year-old African American woman presented to a private dermatologic practice with a 1-year history of pruritic hyperpigmented patches involving the right and left medial scapular back that was confirmed as patch stage MF via biopsy. Initial treatment consisted of 308-nm excimer lamp phototherapy at a dose of 150MED to the affected area which was gradually increased to a range of 160MED to 190MED over the next 18 weeks at 1 to 3-week intervals. After treatment completion a shave biopsy was performed 5 weeks later which confirmed resolution of MF. Discussion: Excimer lamp phototherapy offers shorter therapy duration, targeted treatment, and low UV exposure. This report aims to demonstrate the potential use, safety, and efficacy of the 308-nm excimer lamp in the treatment of patch stage MF. The positive results observed in this report indicate a need for further research and assessment for the potential use of the 308-nm excimer lamp as a therapeutic for early-stage MF.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Biomarkers for Health Functional Foods in Metabolic Dysfunction-Associated Steatotic Liver Disorder (MASLD) Prevention: An Integrative Analysis of Network Pharmacology, Gut Microbiota, and Multi-Omics.

Metabolic dysfunction-associated steatotic liver disorder (MASLD) is increasingly prevalent globally, highlighting the need for preventive strategies and early interventions. This comprehensive review explores the potential of health functional foods (HFFs) to maintain healthy liver function and prevent MASLD through an integrative analysis of network pharmacology, gut microbiota, and multi-omics approaches. We first examined the biomarkers associated with MASLD, emphasizing the complex interplay of genetic, environmental, and lifestyle factors. We then applied network pharmacology to identify food components with potential beneficial effects on liver health and metabolic function, elucidating their action mechanisms. This review identifies and evaluates strategies for halting or reversing the development of steatotic liver disease in the early stages, as well as biomarkers that can evaluate the success or failure of such strategies. The crucial role of the gut microbiota and its metabolites for MASLD prevention and metabolic homeostasis is discussed. We also cover state-of-the-art omics approaches, including transcriptomics, metabolomics, and integrated multi-omics analyses, in research on preventing MASLD. These advanced technologies provide deeper insights into physiological mechanisms and potential biomarkers for HFF development. The review concludes by proposing an integrated approach for developing HFFs targeting MASLD prevention, considering the Korean regulatory framework. We outline future research directions that bridge the gap between basic science and practical applications in health functional food development. This narrative review provides a foundation for researchers and food industry professionals interested in developing HFFs to support liver health. Emphasis is placed on maintaining metabolic balance and focusing on prevention and early-stage intervention strategies.

Therapeutic effects of LIPUS on the elasticity of injured tendons: animal experiment

Abstract This paper aims to explore the efficacy and duration of low-intensity pulsed ultrasound (LIPUS) treatment in improving the elastic properties of injured tendons through animal experiments. 48 healthy 3-month-old New Zealand white rabbits (weight 2.5-3.0 kg) were randomly divided into the Control group (n = 9) and model group (n = 39). The rabbits in the model group were injected with 0.2ml PGE2 mixed solution (concentration: 500 ng/0.2ml) into the Achilles tendon 2cm above the calcaneus, once a week, for 4 weeks, to build the Achilles tendon injury model. The Control group was injected with the same volume of PBS solution. Three rabbits were randomly selected from the Control and model groups for model validation, the model group was randomly divided into the Model (n = 6) and LIPUS (n = 30) groups. Then the LIPUS was randomly divided into the LIPUS1 (n = 6), LIPUS4 (n = 6), LIPUS7 (n = 6), LIPUS14 (n = 6), and LIPUS28 (n = 6) subgroups. Following interventions on days 1, 4, 7, 14, and 28, tendon elasticity was assessed by shear wave elastography (SWE). The elastic modulus of the Model, LIPUS1, and LIPUS4 groups exhibited a significant decrease compared to the Control group during the early stages of treatment. With prolonged treatment duration, the elastic modulus of LIPUS groups gradually increased. By day 7, no statistically significant difference in elastic modulus existed between the LIPUS7 and Control groups, indicating that LIPUS treatment had successfully restored the Achilles tendon’s elasticity to a healthy state. In summary, LIPUS therapy demonstrates the potential to effectively ameliorate the elastic properties of injured Achilles tendons.

Application of extracorporeal membrane oxygenation combined with renal replacement therapy in the treatment of war traumatic sepsis

Sepsis is an important factor for trauma related death, especially the refractory septic shock, which has a mortality rate exceeding 50%. The treatment of sepsis is a medical problem that needs to be solved urgently. The role and status of extracorporeal membrane oxygenation (ECMO) in the treatment of cardiopulmonary failure has become more and more prominent, and its role in the treatment of sepsis in children and infants has gained remarkable achievements. However, its role in adult sepsis remains controversial, with current reports showing varied outcomes for ECMO in adult sepsis treatment. ECMO application can potentially cause renal impairment, and renal impairment can affect the outcomes of ECMO treatment in turn. Studies have shown that adjunctive renal replacement therapy during non-ECMO treatment of septic shock can improve the prognosis, and whether the combination with renal replacement therapy in the early stage of ECMO treatment can effectively improve the treatment outcome still needs to be confirmed by multicenter and prospective studies. Based on this, this article reviews the relevant research on the application of ECMO combined with renal replacement therapy in the treatment of sepsis after war trauma, aiming to provide clinical reference for the treatment of sepsis after war trauma.

An Acceptor-Donor-Acceptor Structured Nano-Aggregate for NIR-Triggered Interventional Photoimmunotherapy of Cervical Cancer.

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η=67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.

Identification of Immune Checkpoint Inhibitor–Induced Diabetes

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy. To define incidence, risk factors, and clinical spectrum of an irreversible and life-threatening irAE: ICI-induced diabetes. This cohort study, conducted at an academic integrated health care system examined 14 328 adult patients treated with ICIs, including 64 patients who developed ICI-induced diabetes, from July 2010 to January 2022. The data were analyzed from 2022 to 2023. Cases of ICI-induced diabetes were manually confirmed; detailed clinical phenotyping was performed at diagnosis and 1-year follow-up. For 862 patients, genotyping data were available, and polygenic risk for type 1 diabetes was determined. For ICI-induced diabetes cases and controls, demographic characteristics, comorbidities, tumor category, and ICI category were compared. Among ICI-induced diabetes cases, markers of glycemic physiology were examined at diagnosis and 1-year follow-up. For patients with available genotyping, a published type 1 diabetes polygenic score (T1D GRS2) was calculated. Of 14 328 participants, 6571 (45.9%) were women, and the median (range) age was 66 (8-106) years. The prevalence of ICI-induced diabetes among ICI-treated patients was 0.45% (64 of 14 328), with an incidence of 124.8 per 100 000 person-years. Preexisting type 2 diabetes (odds ratio [OR], 5.91; 95% CI, 3.34-10.45) and treatment with combination ICI (OR, 2.57; 95% CI, 1.44-4.59) were significant clinical risk factors of ICI-induced diabetes. T1D GRS2 was associated with ICI-induced diabetes risk, with an OR of 4.4 (95% CI, 1.8-10.5) for patients in the top decile of T1D GRS2, demonstrating a genetic association between spontaneous autoimmunity and irAEs. Patients with ICI-induced diabetes were in 3 distinct phenotypic categories based on autoantibodies and residual pancreatic function, with varying severity of initial presentation. The results of this analysis of 14 328 ICI-treated patients followed up from ICI initiation determined the incidence, risk factors and clinical spectrum of ICI-induced diabetes. Widespread implementation of this approach across organ-specific irAEs may enhance diagnosis and management of these conditions, and this becomes especially pertinent as ICI treatment rapidly expands to treat a wide spectrum of cancers and is used at earlier stages of treatment.

Optimizing machine learning algorithms for diabetes data: A metaheuristic approach to balancing and tuning classifiers parameters

Diabetes mellitus poses a global health concern, prompting the development of machine learning algorithms designed to construct a model for the accurate classification of patients, enabling precise diagnoses and early-stage treatment. However, the efficacy of classifying diabetes patients through machine learning relies on datasets, often plagued by imbalance, leading to biased classification and inaccurate diagnoses. Previous research attempts, employing techniques like random sampling (under-sampling and oversampling) and the Synthetic Minority Oversampling Technique (SMOTE), have struggled to achieve optimally balanced datasets. Additionally, setting the best parameters for machine learning classifiers remains a challenging task. To address these issues, this research focuses on devising a methodological metaheuristic optimization, a machine learning algorithm tailored for diabetes data balancing, and classifier hyperparameter tuning. Leveraging Particle Swarm Optimization (PSO) algorithm for diabetes data balancing and a genetic algorithm to select the optimal architecture for various machine learning classifiers. The study compares the performance of the proposed metaheuristic data balancer and classifier architecture parameter tuner using classification metrics (F1 score, Average Precision–Recall (APR), AUC, and accuracy). The PSO balanced dataset emerges as the most effective in classifying diabetes, with an Average Percentage Improvement (API) in classification performance metrics: 20.78% accuracy, 16.79% area under the curve for receiver operating characteristics, and a significant 32.78% enhancement in APR. Moreover, the XGBOOST classifier trained with a genetic algorithm demonstrates minimal computational training time for the Centre for Disease Control and Prevention (CDC) diabetes dataset compared to the artificial neural network and random forest classifier. Notably, the imbalanced CDC diabetes dataset exhibits the least APR compared to random under-sampling and the PSO data balancing technique.

How to ventilate critically ill children with cancer?: a narrative review

Abstract The management of respiratory failure and hypoxemia in children with cancer presents a critical challenge. Choosing between invasive and noninvasive mechanical ventilation can profoundly impact mortality rates, especially in resource-limited settings. Choosing between invasive and noninvasive mechanical ventilation can impact mortality rates, particularly in resource-limited settings. Extensive clinical studies are imperative to thoroughly evaluate the efficacy of invasive mechanical ventilation (IMV) and noninvasive ventilation (NIV) during the early stages of treatment. Further research is crucial to determine the most optimal therapeutic approach. Early implementation of IMV or NIV could significantly reduce mortality rates in these patients.[ 1 ] Additionally, this article examines the admission of children with terminal cancer, evaluating their use of invasive and noninvasive ventilatory support versus palliative care. The interdisciplinary medical team, in collaboration with the family, must carefully consider the benefits and risks of these interventions, whether in the early or terminal stages of the disease. Furthermore, the article delves into the controversies surrounding the utilization of ventilation in critically ill children with cancer.

Anti-HDGF antibody targets EGFR tyrosine kinase inhibitor-tolerant cells in NSCLC patient-derived xenografts.

Constitutively active mutant epidermal growth factor receptor (EGFR) is one of the major oncogenic drivers in NSCLC. Targeted therapy using EGFR tyrosine kinase inhibitor (TKI) is a firstline option in patients that have metastatic or recurring disease. However, despite the high response rate to TKI, most patients have a partial response, and the disease eventually progresses in 10 to 19 months. It is believed that drug-tolerant cells that survive TKI exposure during the progression-free period facilitate the emergence of acquired resistance. Thus, targeting the drug-tolerant cells could improve the treatment of NSCLC with EGFR mutations. We demonstrated here that EGFR mutant patient-derived xenograft (PDX) tumors responded partially to osimertinib despite near complete inhibition of EGFR activation. Signaling in AKT/mTOR and MAPK pathways could be reactivated shortly after initial inhibition. As a result, many tumor cells escaped drug killing and regained growth following about 35 days of continuous osimertinib dosing. However, when an antibody to hepatoma-derived growth factor (HDGF) was given concurrently with osimertinib, tumors showed complete or near-complete responses.There was significant prolongation of progression-free survival (PFS) of tumor-bearing mice as well. Immunohistochemistry and western blot analysis of tumors collected in the early stages of treatment suggest that increased suppression of the AKT/mTOR and MAPK pathways could be a mechanism that results in enhanced efficacy of osimertinib when it is combined with anti-HDGF antibody.

Efficacy and mechanism of the Ermiao San series of formulas for rheumatoid arthritis based on Chinmedomics strategy

BackgroundThe Ermiao San Series of Formulas (ESSF) refers to Ermiao San (TS), Sanmiao Wan (TW), and Simiao Wan (FW), which are widely used traditional Chinese medicine (TCM) formulas for treating rheumatoid arthritis (RA). However, the therapeutic advantages and underlying mechanisms of ESSF treatment are unclear, especially regarding the improper selection of these three formulas when treating RA. PurposeTo explore the efficacy and mechanisms of ESSF treatment for RA. MethodsComplete Freund's adjuvant was used to induce RA in rats. Chinmedomics strategy, which included metabolomics, serum pharmacochemistry of TCM, molecular docking, western blotting and qPCR, was applied to reveal the therapeutic advantages, pathways, and targets of ESSF. ResultsIn the early stages of treatment, TS quickly reduced joint swelling and the arthritis score index and regulated pathways such as arachidonic acid metabolism and purine metabolism. TW increases the regulation of tryptophan metabolism and pyrimidine metabolism pathways, promoting the recovery of the thymus and spleen. FW increases the regulation of linoleic acid metabolism and has the greatest effect on immune organ and bone recovery. In addition, 54, 67, and 86 bioactive compounds were detected in the serum from TS, TW, and FW, respectively. Berberine, phellodendrine, atractylolide III, limonin, 25R-inokosterone, coixol, and stigmasterol were found to act on the key enzymes COX-2, mPGES-1, ALOX5, and XDH in arachidonic acid metabolism and purine metabolism pathways. Western blot and qPCR results showed that ESSF can reduce the activity of these targets, thereby inhibiting the expression of the inflammatory factors IL-1β, IL-6, IL-17, and TNF-α; the tissue injury factors MMP-3 and CRP; and the rheumatoid factors CCP Ab and RF, thereby achieving anti-RA efficacy. ConclusionESSF has a good therapeutic effect on RA. TS focus on rapid swelling reduction in the early stages of RA, TW focus on the recovery of immune organ function, and FW can be used for bone recovery in the later stage of RA treatment. The key mechanism of treating RA is that ESSF reduces the activity of COX-2, mPGES-1, ALOX5, and XDH. These findings provide valuable guidance for targeted therapy for RA and for the clinical application of ESSF.

Close Cardiovascular Monitoring during the Early Stages of Treatment for Patients Receiving Immune Checkpoint Inhibitors.

Background: There is an unmet medical need for the early detection of immune checkpoint inhibitor (ICI)-induced cardiovascular (CV) adverse events due to a lack of adequate biomarkers. This study aimed to provide insights on the incidence of troponin elevations and echocardiographic dynamics during ICI treatment in cancer patients and their role as potential biomarkers for submyocardial damage. In addition, it is the first study to compare hs-TnT and hs-TnI in ICI-treated patients and to evaluate their interchangeability in the context of screening. Results: Among 59 patients, the mean patient age was 68 years, and 76% were men. Overall, 25% of patients received combination therapy. Although 10.6% [95% CI: 5.0-22.5] of the patients developed troponin elevations, none experienced a CV event. No significant changes were found in 3D left ventricular (LV) ejection fraction nor in global longitudinal strain f (56 ± 6% vs. 56 ± 6%, p = 0.903 and -17.8% [-18.5; -14.2] vs. -17.0% [-18.8; -15.1], p = 0.663) at 3 months. There were also no significant changes in diastolic function and right ventricular function. In addition, there was poor agreement between hs-TnT and hs-TnI. Methods: Here, we present a preliminary analysis of the first 59 patients included in our ongoing prospective clinical trial (NCT05699915) during the first three months of treatment. All patients underwent electrocardiography and echocardiography along with blood sampling at standardized time intervals. This study aimed to investigate the incidence of elevated hs-TnT levels within the first three months of ICI treatment. Elevations were defined as hs-TnT above the upper limit of normal (ULN) if the baseline value was normal, or 1.5 ≥ times baseline if the baseline value was above the ULN. Conclusions: Hs-TnT elevations occurred in 10.6% of the patients. However, no significant changes were found on 3D echocardiography, nor did any of the patients develop a CV event. There were also no changes found in NT-proBNP. The study is still ongoing, but these preliminary findings do not show a promising role for cardiac troponins nor for echocardiographic dynamics in the prediction of CV events during the early stages of ICI treatment.

An International Registry Study of Early-Stage NSCLC treatment variations (LUCAEUROPE) in Europe and the USA highlighting variations

ObjectiveHarmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear. Summary background dataSurgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization. MethodsThe retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010–2015. ResultsThe study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes. ConclusionsResection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment.

Main active constituents and mechanism of toxicity of raphides from Arisaema erubescens against Oncomelania hupensis

To find a high-efficiency and environment-friendly biogenic molluscicide against Oncomelania hupensis, and prevent aquatic ecosystem from being contaminated by chemical molluscicides and being toxic. We extracted and purified raphides from the tubers of Arisaema erubescent, and determined the active constituents and molluscicidal activity of the raphides, detoxification enzyme activity, and liver damage. The results showed that the raphides had a strong molluscicidal activity. O. hupensis snails were exposed to the lethal concentration (LC50) of 70.95 mg/L and 44.25 mg/L for treatment with raphides for 48 h and 72 h, respectively. The raphides of molluscicidal activity of the main constituents was as follows: intact raphides > calcium oxalate crystals > AEL (Arisaema erubescens Lectin). The activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) in the snail livers increased significantly at the early stage of treatment (24 h), but decreased sharply in the later stage (120 h), compared with that in the control group. The results indicated that after treatment with 1/2 LC50 raphides for 120 h, the activities of POD, SOD, and CAT in the snail livers decreased by 82.5 %, 62.9 %, and 84.7 %, respectively. In addition, electron micrographs have shown that the raphides were needle-shaped crystals and tended to be sharp at both ends (with a groove down both sides) and some were barbed, which caused damage to the snail livers to different extent. Overall, our results indicate that the mechanism of toxicity of raphides against O. hupensis may be that the calcium oxalate crystals pricked the liver surface of snail and produced mechanical damage; and then the harmful protease AEL in the raphides was injected into the liver, which reduced the activities of detoxification enzymes, produced severe toxic reactions and eventually killed the O. hupensis snails.

Fruits and vegetables dietary intake and its estimated consumption among adults receiving antiretroviral therapy in health facilities in Northcentral Ethiopia: a multi-facility cross-sectional study.

Despite the significant role of fruit and vegetables (FAVs) in preventing a variety of chronic diseases and their potential to bolster immune responses and slow the progression of HIV infection to AIDS, there is a lack of studies on the dietary intake of FAVs among HIV-infected adults in Africa, including Ethiopia. Hence, this study aimed to investigate the magnitude of FAV intake and estimated consumption among HIV-infected adults receiving antiretroviral therapy (ART) in northcentral Ethiopia. A multifacility cross-sectional study was conducted on the FAV intake among 865 HIV-infected adults receiving ART. A Poisson regression model with robust variance was used to identify factors associated with FAVs dietary intake. The study indicated that 655 (76.34%; 95% CI: 73.38, 79.07) HIV-infected adults reported consuming FAVs less than once per day, with 838 (97.67%, 95% CI: 96.41, 98.49) and 676 (78.79%, 95% CI: 75.92, 81.40) HIV-infected adults reporting consuming fruits and vegetables less than once per day, respectively. The median (IQR) total FAV intake was 271.3 (IQR: 92.5, 439.5) g/day, with the median (IQR) intake of fruits being 248.1 (IQR: 100.0, 400.0) g/day and vegetables being 273.78 (IQR: 82.44, 348.33) g/day, respectively. We found that being divorced (APR = 1.57, 95% CI: 1.16, 2.12), employed as a daily laborer (APR = 2.08, 95% CI: 1.36, 3.20), being employed (APR = 1.77, 95% CI: 1.10, 2.84), merchants (APR = 1.59, 95% CI: 1.03, 2.47), having children as caregivers (APR = 1.61, 95% CI: 1.02, 2.55), an advanced WHO clinical stage (APR = 1.32, 95% CI: 1.32(1.03, 1.69), and receiving ART for more than 8 years (APR = 1.78, 95% CI: 1.18, 2.67) were found to be independent predictors of FAV dietary intake among HIV-infected adults. From the findings, we understood that farmers were less likely to consume FAVs compared to employed individuals, daily laborers, and merchants. The finding indicated a very low level of FAV dietary intake among HIV-infected adults receiving ART, falling well-below the minimum recommendation for physically active adults. Despite living in areas with surplus production and producing these items, farmers are less likely to consume FAV. The study emphasizes the importance of focusing on the early stage of ART treatment for patients and family therapy, including counseling and guidance on consuming healthy diets such as FAVs, to enhance the role of children as caregivers for their families. Additionally, there is a need for comprehensive nutritional counseling to improve FAV consumption, with a particular emphasis on educating individuals about portion size estimation for the consumption of FAVs.

Evaluating therapeutic potential of NR2E3 doses in the rd7 mouse model of retinal degeneration

Retinitis Pigmentosa is a leading cause of severe vision loss. Retinitis Pigmentosa can present with a broad range of phenotypes impacted by disease age of onset, severity, and progression. This variation is influenced both by different gene mutations as well as unique variants within the same gene. Mutations in the nuclear hormone receptor 2 family e, member 3 are associated with several forms of retinal degeneration, including Retinitis Pigmentosa. In our previous studies we demonstrated that subretinal administration of one Nr2e3 dose attenuated retinal degeneration in rd7 mice for at least 3 months. Here we expand the studies to evaluate the efficacy and longitudinal impact of the NR2E3 therapeutic by examining three different doses administered at early or intermediate stages of retinal degeneration in the rd7 mice. Our study revealed retinal morphology was significantly improved 6 months post for all doses in the early-stage treatment groups and for the low and mid doses in the intermediate stage treatment groups. Similarly, photoreceptor function was significantly improved in the early stage for all doses and intermediate stage low and mid dose groups 6 months post treatment. This study demonstrated efficacy in multiple doses of NR2E3 therapy.

Dynamic nanomechanical characterization of cells in exosome therapy

Exosomes derived from mesenchymal stem cells (MSCs) have been confirmed to enhance cell proliferation and improve tissue repair. Exosomes release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression, which is the main pathway through which exosomes exert therapeutic effects. The corresponding process of exosome internalization mainly occurs in the early stage of treatment. However, the therapeutic effect of exosomes in the early stage remains to be further studied. We report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells, serving as an effective method to characterize the therapeutic effect of exosomes. Compared with traditional biochemical methods, we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction force. Through quantitative analysis of traction forces, we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome therapy. Further experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway, thereby promoting cell proliferation. This work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.

Data mining study on adverse events of tirzepatide based on FAERS database

ABSTRACT Background Tirzepatide is a novel dual gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 receptor agonist (GLP-1 RA) for type 2 diabetes or obesity. To explore the safety profile of tirzepatide in real-world clinical applications. Research design and methods A retrospective analysis of adverse events (AEs) reports associated with tirzepatide was conducted from the second quarter of 2022 through the fourth quarter of 2023, utilizing the FDA Adverse Event Reporting System (FAERS) database. Signal mining utilized the reporting odds ratio (ROR) method, and onset time was analyzed utilizing the Weibull Shape Parameter (WSP). Results We identified 25,215 AE reports related to tirzepatide, predominantly in the 65 to 85 age group. Four positive signals were found at the system organ classes level. Additionally,109 AEs at the preferred terms level with positive signals were indicated. Included among these are novel signals, such as the presence of thyroid mass, medullary thyroid carcinoma, and conditions affecting the reproductive system and breast. Most AEs occurred within the first 30 days. The WSP was 0.66, indicating a propensity for early failure type. Conclusions This study identified several novel AE signals for tirzepatide, highlighting the need for careful monitoring, especially in the early stages of treatment.