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Chinese Journal of Integrative Medicine Jun 2024To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application,...
OBJECTIVE
To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation.
METHODS
Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways.
RESULTS
Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot.
CONCLUSION
LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.
PubMed: 38941043
DOI: 10.1007/s11655-024-3717-5 -
Applied Biochemistry and Biotechnology Jun 2024Chronic stress has been linked to a large number of pathologies, including cancer, premature aging, and neurodegenerative diseases. The accumulation of molecular waste...
Chronic stress has been linked to a large number of pathologies, including cancer, premature aging, and neurodegenerative diseases. The accumulation of molecular waste resulting from oxidative and heavy metal-induced stress has been ascribed as a major factor contributing to these diseases. With this in mind, we started by screening 13 small molecules to determine their antistress potential in heavy metal stress-exposed C6 glioblastoma and found that alpha-lipoic acid (ALA) (a natural antioxidant abundantly present in yeast, spinach, broccoli, and meat) was the most effective candidate. We then conducted molecular analyses to validate its mechanism of action. Dose-dependent toxicity assays of cells treated with two ALA enantiomers, R-ALA and S-ALA, showed that they are nontoxic and can be tolerated at relatively high doses. Cells exposed to heavy metal, heat, and oxidative stress showed better recovery when cultured in R-ALA-/S-ALA-supplemented medium, supported by reduction of reactive oxygen species (ROS), aggregated proteins, and mitochondrial and deoxyribonucleic acid (DNA) damage. Molecular analyses revealed protection against stress-induced apoptosis and induction of autophagy in R-ALA- and S-ALA-treated C6/U2OS cells. Consistent with these findings, normal human fibroblasts showed lifespan extension. Taken together, this study demonstrates that lipoic acid has antiaging and antistress potential and warrants further attention in laboratory and clinical studies.
PubMed: 38941028
DOI: 10.1007/s12010-024-04994-4 -
Digestive Diseases and Sciences Jun 2024Drainage of pancreatic fluid collections (PFCs) is required in select cases including infected or symptomatic collections. In this network meta-analysis, we have...
BACKGROUND AND AIMS
Drainage of pancreatic fluid collections (PFCs) is required in select cases including infected or symptomatic collections. In this network meta-analysis, we have compared lumen-apposing metal stents (LAMS), fully covered self-expandable metal stents (FCSEMS), and double-pigtail stents (DPS) to identify the most useful stent type in the management of PFCs.
METHODS
We reviewed several databases to identify studies that compared DPS or FCSEMS with LAMS and the ones which compared DPS with FCSEMS for the treatment of PFCs. Our outcomes of interest were clinical success, adverse events, technical success, recurrence of PFCs, and procedure duration. Random effects model and frequentist approach were used for statistical analysis.
RESULTS
We included 28 studies with 2974 patients. Rate of clinical success was significantly lower with DPS compared to LAMS, OR (95% CI): 0.43 (0.32, 0.59). Rate of recurrence was higher with DPS compared to LAMS, OR (95% CI): 2.06 (1.19, 3.57). We found no significant difference in rate of adverse events between groups. Rate of technical success was higher for FCSEMS compared to LAMS. Procedure duration was significantly shorter for LAMS compared to DPS and FCSEMS. Based on frequentist approach, LAMS was found to be superior to DPS and FCSEMS in achieving higher clinical success, lower rate of adverse events and recurrence, and shorter procedure time.
CONCLUSIONS
This network meta-analysis demonstrates the superiority of LAMS over DPS and FCSEMS in the management of PFCs in achieving a higher clinical success, shorter procedure time, and lower rate of recurrence. Some of the analyses are not adequately powered to make firm conclusions, and future large multicenter RCTs are required to further evaluate this issue.
PubMed: 38940974
DOI: 10.1007/s10620-024-08538-y -
Clinical and Experimental Medicine Jun 2024Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for... (Comparative Study)
Comparative Study
Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for advanced hepatocellular carcinoma (HCC) in China. Different efficacy between the two regimens combined with transvascular intervention for unresectable HCC (uHCC) remain unknown. We retrospectively analyzed uHCC patients treated in three centers by simultaneous combination of A+B or S+B with transarterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs) were compared. Totally 188 patients were included, with 92 and 96 administered A+B+TACE-HAIC (ABTH) and S+B+TACE-HAIC (SBTH), respectively. ORRs (62.0 vs. 70.8%, respectively; P = 0.257) and disease control rates (88.0 vs. 93.8%, P = 0.267) were similar between groups by the mRECIST criteria. ABTH showed no survival advantage over SBTH, with median PFS times of 11.7 months and 13.0 months, respectively (HR = 0.81, 95% CI, 0.52-1.26, P = 0.35) and similar OS times (HR = 1.19, 95% CI, 0.32-4.39, P = 0.8). No significant differences were observed in grade 3-4 TRAEs between groups. Either PD-L1 or PD-1 inhibitor plus bevacizumab combined with TACE-HAIC have similarly excellent therapeutic efficacy with manageable adverse events, representing promising treatment options for uHCC.
Topics: Humans; Carcinoma, Hepatocellular; Male; Bevacizumab; Middle Aged; Female; Liver Neoplasms; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Antibodies, Monoclonal, Humanized; Treatment Outcome; Immune Checkpoint Inhibitors; China; Chemoembolization, Therapeutic; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Fluorouracil; Leucovorin
PubMed: 38940944
DOI: 10.1007/s10238-024-01415-y -
Skeletal Radiology Jun 2024Fatty infiltration of skeletal muscle (Myosteatosis) is associated with increased frailty, decreased muscle and mobility function, which seems fairly prevalent in...
OBJECTIVE
Fatty infiltration of skeletal muscle (Myosteatosis) is associated with increased frailty, decreased muscle and mobility function, which seems fairly prevalent in multiple myeloma (MM) patients. This study aimed to determine the prognostic value of myosteatosis assessed by CT for progression-free survival (PFS) and overall survival (OS).
MATERIALS AND METHODS
This IRB-approved cohort study included patients with newly diagnosed MM who were treated at a single university hospital and received CT at baseline. Geriatric assessment was performed via International Myeloma Working Group frailty score and Revised Myeloma Comorbidity Index. Myosteatosis was determined through measurement of paravertebral muscle radiodensity. Statistical analyses included uni- and multivariable Cox proportional hazard models and the Kaplan-Meier-method.
RESULTS
A total of 226 newly diagnosed MM patients (median age: 65 years [range: 29-89], 63% males, mean BMI: 25 [14-42]) were analyzed. The prevalence of myosteatosis was 51%. Muscle radiodensity was significantly decreased in individuals with International Staging System stage III vs. I (p < 0.001), indicating higher fatty muscle infiltration in patients with advanced disease. Both PFS and OS were significantly decreased in patients with myosteatosis (PFS: median 32.0 months (95% CI 20.5.5-42.2) vs. 66.4 months without myosteatosis (95% CI 42.5-not reached), p < .001); OS: median 58.6 (95% CI 51.3-90.2) vs. not reached, p < .001). Myosteatosis remained an independent predictor of OS in multivariable analyses (HR: 1.98; 95%-CI: 1.20-3.27).
CONCLUSION
Myosteatosis seems fairly prevalent in patients with newly diagnosed MM and associated with impaired overall survival. Prospective clinical trials are required to better understand the role of myosteatosis in MM patients.
PubMed: 38940940
DOI: 10.1007/s00256-024-04735-y -
Abdominal Radiology (New York) Jun 2024Prostate magnetic resonance imaging (MRI) stands as the cornerstone in diagnosing prostate cancer (PCa), offering superior detection capabilities while minimizing... (Review)
Review
Prostate magnetic resonance imaging (MRI) stands as the cornerstone in diagnosing prostate cancer (PCa), offering superior detection capabilities while minimizing unnecessary biopsies. Despite its critical role, global disparities in MRI diagnostic performance persist, stemming from variations in image quality and radiologist expertise. This manuscript reviews the challenges and strategies for enhancing image quality in prostate MRI, spanning patient preparation, MRI unit optimization, and radiology team engagement. Quality assurance (QA) and quality control (QC) processes are pivotal, emphasizing standardized protocols, meticulous patient evaluation, MRI unit workflow, and radiology team performance. Additionally, artificial intelligence (AI) advancements offer promising avenues for improving image quality and reducing acquisition times. The Prostate-Imaging Quality (PI-QUAL) scoring system emerges as a valuable tool for assessing MRI image quality. A comprehensive approach addressing technical, procedural, and interpretative aspects is essential to ensure consistent and reliable prostate MRI outcomes.
PubMed: 38940911
DOI: 10.1007/s00261-024-04396-4 -
Annals of Surgical Oncology Jun 2024Persons assigned female or intersex at birth and identify as transgender and/or gender-diverse (TGD) may undergo gender-affirming chest masculinization surgery (GACMS);...
The Impact of a Breast Cancer Risk Assessment on the Decision for Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Individuals: A Pilot Single-Arm Educational Intervention Trial.
BACKGROUND
Persons assigned female or intersex at birth and identify as transgender and/or gender-diverse (TGD) may undergo gender-affirming chest masculinization surgery (GACMS); however, GACMS is not considered equivalent to risk-reducing mastectomies (RRM). This study aimed to estimate the prevalence of elevated breast cancer (BC) risk in TGD persons, compare self-perceived versus calculated risk, and determine how risk impacts the decision for GACMS versus RRM.
METHODS
A prospective single-arm pilot educational intervention trial was conducted in individuals assigned female or intersex at birth, age ≥ 18 years, considering GACMS, without a BC history or a known pathogenic variant. BC risk was calculated using the Tyrer-Cuzik (all) and Gail models (age ≥ 35 years). Elevated risk was defined as ≥ 17%.
RESULTS
Twenty-five (N = 25) participants were enrolled with a median age of 24.0 years (interquartile range, IQR 20.0-30.0 years). All were assigned female sex at birth, most (84%) were Non-Hispanic (NH)-White, 48% identified as transgender and 40% as nonbinary, and 52% had a first- and/or second-degree family member with BC. Thirteen (52%) had elevated risk (prevalence 95% confidence interval (CI) 31.3-72.2%). Median self-perceived risk was 12% versus 17.5% calculated risk (p = 0.60). Of the 13 with elevated risk, 5 (38.5%) underwent/are scheduled to undergo GACMS, 3 (23%) of whom underwent/are undergoing RRM.
CONCLUSIONS
Over half of the cohort had elevated risk, and most of those who moved forward with surgery chose to undergo RRM. A BC risk assessment should be performed for TGD persons considering GACMS. Future work is needed to examine BC incidence and collect patient-reported outcomes. Trial Registration Number ClinicalTrials.gov (No. NCT06239766).
PubMed: 38940898
DOI: 10.1245/s10434-024-15701-2 -
Alternative Therapies in Health and... Jun 2024We aimed to explore the effect of personalized psychological nursing on the quality of life (QoL) in patients with advanced lung cancer (ALC).
OBJECTIVE
We aimed to explore the effect of personalized psychological nursing on the quality of life (QoL) in patients with advanced lung cancer (ALC).
METHODS
A total of 126 patients with ALC who were admitted to The First People's Hospital of Fuyang District in China from March 2018 to March 2021 were selected as study participants. They were randomly assigned to either the control group or the study group. The degree of anxiety, depression, cancer-related fatigue, sleep quality, QoL and treatment compliance in the 2 groups were observed and compared.
RESULTS
HAM-D (Hamilton Depression Rating Scale), HAM-A (Hamilton Anxiety Rating Scale) and (PFS-R) scores in the 2 groups after nursing were lower, and those in the study group were significantly lower (P < .05). The Pittsburgh Sleep Quality Index (PSQI) scale scores in the study group after nursing were lower than in the control group (P < .05). After nursing, body, role, cognition, emotion, social function and overall QoL in the study group were significantly higher than in the control group (P < .05). The nursing compliance in the study group was 96.83%, significantly higher than in the control group (88.89%) (P < .05).
CONCLUSION
The implementation of personalized psychological nursing for patients with ALC can alleviate anxiety, depression and cancer-related fatigue, improve their sleep quality and QoL and improve medication compliance, which is worthy of clinical promotion.
PubMed: 38940782
DOI: No ID Found -
Alternative Therapies in Health and... Jun 2024The objective of this study is to develop a prediction model for the pathological upgrading of low-grade dysplasia (LGD) in gastric mucosa. The study aims to compare the...
OBJECTIVE
The objective of this study is to develop a prediction model for the pathological upgrading of low-grade dysplasia (LGD) in gastric mucosa. The study aims to compare the performance of a traditional model based on clinical and endoscopic factors with an enhanced model that incorporates AMACR staining of biopsy tissues.
METHODS
The study utilized a training dataset of 405 LGD cases to establish and compare the traditional and enhanced prediction models. Factors associated with upgrading were identified, and the traditional model was based on these factors. The enhanced model incorporated AMACR staining. The models' performances were evaluated using the area under the curve (AUC), bootstrap resampling, and decision curve analysis. External validation was performed using 171 LGD cases. Statistical techniques such as logistic regression and resampling methods were employed to assess the models' predictive abilities and robustness.
RESULTS
In the training dataset, the traditional model achieved an AUC of 0.824 (95% confidence interval [CI]: 0.783-0.865) for predicting pathological upgrading. However, the enhanced model, which incorporated AMACR staining, exhibited a significantly improved performance with an AUC of 0.878 (95% CI: 0.843-0.913). This increase in AUC by 0.054 (95% CI: 0.015-0.093) demonstrates a statistically significant enhancement provided by the inclusion of AMACR staining in the prediction model for pathological upgrading of LGD lesions in gastric mucosa.
CONCLUSION
The findings of this study highlight the practical implications of the enhanced prediction model incorporating AMACR staining for low-grade gastric mucosal dysplasia (LGD). The significantly improved performance of the enhanced model in predicting pathological upgrading emphasizes its potential to revolutionize the management and treatment strategies for patients with LGD. By providing a more accurate prediction of upgrading, the enhanced model enables early intervention and timely decision-making, leading to improved outcomes and prognosis for patients. The incorporation of AMACR staining in the prediction model holds promise for enhancing diagnostic strategies and reducing the incidence of postoperative pathological upgrading. This research underscores the importance of leveraging advanced techniques to improve the early detection rate of gastric cancer and ultimately benefit patient care.
PubMed: 38940773
DOI: No ID Found -
Thyroid : Official Journal of the... Jun 2024Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harbouring BRAFV600E(PTC-BRAF) confers a worse prognosis,...
BACKGROUND
Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harbouring BRAFV600E(PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC.
OBJECTIVE
We compared prevalence of PTC-BRAF with and without LT. The risk of adverse pathologic features in (i) PTC-BRAF, irrespective of LT status, was compared to (ii)PTC with LT, irrespective of BRAF status.
METHODS
We searched PubMed, Embase and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features and the quality assessment tool was extracted by two reviewers.
RESULTS
Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated the odds of PTC-BRAF was significantly lower in the presence on LT compared to its absence (OR 0.53, 95% CI: 0.48-0.58, p<0.00001). In PTC-BRAF patients, there was positive association of central neck nodal disease (CNND), PTC>1cm, extra-thyroidal extension, AJCC Stage 3-4 and multifocality with pooled OR 1.54 (95%CI:1.16-2.04), 1.14 (95%CI: 0.82- 1.58) , 1.66 (95%CI: 1.40-1.97), 1.53 (95% CI: 1.35-1.75) and 1.24 (95%CI: 1.11-1.40) respectively, compared to wild type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled OR of 0.64 (95%CI: 0.51-0.81) for CNND, 0.83 (95%CI: 0.73 - 0.95) for PTC> 1cm, 0.71 (95%CI: 0.58-0.86) for ETE, 0.84 (95%CI: 0.75-0.94) for AJCC Stage 3-4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT with pooled OR of 1.12 (95%CI: 0.66-1.90, p=0.67) and 0.60 (95%CI: 0.28-1.30, p=0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set.
CONCLUSION
The odds of PTC-BRAF is significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and weather this is relevant to the role of immunotherapy in advanced thyroid cancer.
PubMed: 38940753
DOI: 10.1089/thy.2024.0142