Exploration of the Molecular Mechanism of Curcuma aromatica Salisb's Anticolorectal Cancer Activity via the Integrative Approach of Network Pharmacology and Experimental Validation.

Curcuma aromatica Salisb (Cur), a well-known herbal medicine, has a wide spectrum of anti-inflammatory, anticarcinogenic, and antioxidant activities. However, the roles of its active compounds and potential mechanisms in colorectal cancer remain unknown. This research utilized network pharmacology and experimental validation to explore the possible mechanisms by which Cur protects against colorectal cancer. The active compounds of Cur and related genes for colorectal cancer were obtained from public databases. The DrugBank database was used to search for anticolorectal cancer drugs licensed through the FDA and their targets, and a "drug-component-target" relationship network was created using the Cytoscape program. The String database produced the PPI network. The ability of these active ingredients to bind to core targets was confirmed by molecular docking using AutoDock Vina. Cell and animal experiments were then carried out. A total of 274 targets were obtained from Cur, 49 of which were potential therapeutic targets. Four key targets, PTGS2, AKT1, TP53, and estrogen receptor 1 (ESR1), were screened via the PPI network and the FDA drug-target network. Molecular docking results revealed that Cur had strong binding abilities to these targets. In vivo and in vitro experiments demonstrated that Cur suppressed the development of colorectal cancer by regulating its targets (PTGS2, AKT1, TP53, and ESR1), which play crucial roles in promoting apoptosis and suppressing cell proliferation, migration, and invasion. Collectively, Cur protects against colorectal cancer by regulating the AKT1/PTGS2/ESR1 and P53 pathways, which lays the groundwork for further research and clinical applications of Cur in colorectal cancer therapy.

Comparison of three frailty scales for prediction of prolonged postoperative ileus following major abdominal surgery in elderly patients: a prospective cohort study.

BACKGROUND: To determine whether frailty can predict prolonged postoperative ileus (PPOI) in older abdominal surgical patients; and to compare predictive ability of the FRAIL scale, the five-point modified frailty index (mFI-5) and Groningen Frailty Indicator (GFI) for PPOI. METHODS: Patients (aged ≥ 65 years) undergoing major abdominal surgery at our institution between April 2022 to January 2023 were prospectively enrolled. Frailty was evaluated with FRAIL, mFI-5 and GFI before operation. Data on demographics, comorbidities, perioperative management, postoperative recovery of bowel function and PPOI occurrence were collected. RESULTS: The incidence of frailty assessed with FRAIL, mFI-5 and GFI was 18.2%, 38.4% and 32.5% in a total of 203 patients, respectively. Ninety-five (46.8%) patients experienced PPOI. Time to first soft diet intake was longer in patients with frailty assessed by the three scales than that in patients without frailty. Frailty diagnosed by mFI-5 [Odds ratio (OR) 3.230, 95% confidence interval (CI) 1.572-6.638, P = 0.001] or GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) was related to a higher risk of PPOI. Both mFI-5 [Area under curve (AUC) 0.653, 95% CI 0.577-0.730] and GFI (OR 2.627, 95% CI 1.307-5.281, P = 0.007) had insufficient accuracy for the prediction of PPOI in patients undergoing major abdominal surgery. CONCLUSIONS: Elderly patients diagnosed as frail on the mFI-5 or GFI are at an increased risk of PPOI after major abdominal surgery. However, neither mFI-5 nor GFI can accurately identify individuals who will develop PPOI. TRIAL REGISTRATION: This study was registered in Chinese Clinical Trial Registry (No. ChiCTR2200058178). The date of first registration, 31/03/2022, https://www.chictr.org.cn/ .

Bilirubin ameliorates osteoarthritis via activating Nrf2/HO-1 pathway and suppressing NF-κB signalling.

Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti-inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS-treated Raw264.7 cells to test the anti-inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS-treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO-1 pathway and suppressing NF-κB signalling. An ACLT-induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.

Molecular Mechanism of Salvia miltiorrhiza in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology.

Purpose: This study aimed to investigate the effect of Salvia miltiorrhiza on colorectal cancer, as well as the mechanisms involved. Methods: The active compounds of Salvia miltiorrhiza and the associated genes in colorectal cancer were sourced from publicly available databases. Targets associated with colorectal cancer were identified by searching the GeneCards and OMIM databases. Subsequently, the Cytoscape 3.6.0 software was employed to create a regulatory network that illustrates the relationships among active ingredients, colorectal cancer, and their corresponding targets. The String database was utilized to generate a PPI network. Molecular docking studies, conducted with AutoDock Vina, verified the binding capabilities of these active components to core targets. The findings from network pharmacology analysis were corroborated through in vitro experiments. Results: In this study, we identified 39 active components derived from Salvia miltiorrhiza that are predicted to target 544 genes associated with colorectal cancer through network pharmacology. Through a combined analysis of network pharmacology, we isolated three key targets: SRC, IL6, and INS. Molecular docking results convincingly demonstrated Salvia miltiorrhiza's strong binding affinity to these targets. Additionally, in vitro experiments confirmed that Salvia miltiorrhiza effectively inhibited the progression of colorectal cancer via regulating the INS/SRC/IL6 pathway. Conclusion: Salvia miltiorrhiza emerges as a compelling herbal intervention for colorectal cancer. This study lays the foundation for potential future clinical trials assessing the efficacy of Salvia miltiorrhiza in the management of colorectal cancer.

Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression.

BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.

Graphene quantum dots promote migration and differentiation of periodontal ligament stem cells.

Graphene and its derivatives have attracted much attention as nanomaterials in bone tissue engineering because of their remarkable ability to induce cell osteogenic differentiation. However, graphene quantum dots (GQDs), as graphene derivatives, little is known about their osteodifferentiation- and osteoinduction-promoting capabilities, especially in the restoration of bone defect caused by periodontitis. Therefore, there is a growing need to investigate the effect of GQDs on periodontal ligament stem cells (PDLSCs). Here, we postulated that GQDs are a promising biocompatible nanomaterial that facilitated the migration and differentiation of PDLSCs, and use laboratory methods like CCK-8, transwell experiments, qRT-PCR, Alizarin red staining and immunofluorescence staining to evaluate. Our experiments confirmed that GQDs did not inhibit cell viability, with most cells remaining viable even at GQDs concentrations of up to 30 µg mL-1. Moreover, GQDs were found to significantly enhance PDLSC migration, with the peak effect observed at concentrations of 5 and 10 µg mL-1. Furthermore, GQDs accelerated osteoblastic differentiation in PDLSCs and induced the mineralization of calcium nodules. Additionally, GQDs were shown to promote fibroblast differentiation in PDLSCs compared to the control group. Thus, GQDs not only possessed low cytotoxicity and good biocompatibility, but also displayed the beneficial capability to migration and differentiation of PDLSCs, which indicated GQDs might be a potential nanomaterial for bone regeneration.

Association of Dietary Intake of Zinc and Selenium with Breast Cancer Risk: A Case-Control Study in Chinese Women.

As major nonenzymatic antioxidant components in the body, dietary Zinc (Zn) and Selenium (Se) may have an impact on breast cancer development. This study aimed to investigate the relationship between dietary Zn, Se intake and breast cancer risk in Chinese women. The case-control study included 1591 cases and 1622 age-frequency matched controls. Dietary intake was collected using a validated food frequency questionnaire. Dietary Zn and Se were divided into four categories: Zn/Se from plants, Zn/Se from meat, Zn/Se from red meat, and Zn/Se from white meat. Unconditional logistic regression models and restricted cubic spline analyses were performed to identify potential associations. Zn from white meat intake was linearly and inversely associated with breast cancer risk, and Se from red meat intake was linearly and positively associated with breast cancer risk, with adjusted odds ratio and 95% confidence interval of 0.76 (0.61-0.95) and 1.36 (1.04-1.77), respectively. Non-linear relationships were found between total dietary Zn, Zn from meat, Zn from red meat intake and breast cancer risk (pnon-linearity < 0.05). In conclusion, dietary Zn and Se intake were associated with breast cancer risk in Chinese women, and the optimal intake of Zn may be beneficial for breast cancer prevention.

Fe-involved nanostructures act as photothermal transduction agents in cancer photothermal therapy.

Cancer, a disease notorious for its difficult therapy regimen, has long puzzled researchers. Despite attempts to cure cancer using surgery, chemotherapy, radiotherapy, and immunotherapy, their effectiveness is limited. Recently, photothermal therapy (PTT), a rising strategy, has gained attention. PTT can increase the surrounding temperature of cancer tissues and cause damage to them. Fe is widely used in PTT nanostructures due to its strong chelating ability, good biocompatibility, and the potential to induce ferroptosis. In recent years, many nanostructures incorporating Fe3+ have been developed. In this article, we summarize PTT nanostructures containing Fe and introduce their synthesis and therapy strategy. However, PTT nanostructures containing Fe are still in their infancy, and more effort must be devoted to improving their effectiveness so that they can eventually be used in clinics.

Transcription factor glucocorticoid modulatory element-binding protein 1 promotes hepatocellular carcinoma progression by activating Yes-associate protein 1.

BACKGROUND: Glucocorticoid modulatory element-binding protein 1 (GMEB1), which has been identified as a transcription factor, is a protein widely expressed in various tissues. Reportedly, the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers. AIM: To explore GMEB1's biological functions in hepatocellular carcinoma (HCC) and figuring out the molecular mechanism. METHODS: GMEB1 expression in HCC tissues was analyzed employing the StarBase database. Immunohistochemical staining, Western blotting and quantitative real-time PCR were conducted to examine GMEB1 and Yes-associate protein 1 (YAP1) expression in HCC cells and tissues. Cell counting kit-8 assay, Transwell assay and flow cytometry were utilized to examine HCC cell proliferation, migration, invasion and apoptosis, respectively. The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter. Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region. RESULTS: GMEB1 was up-regulated in HCC cells and tissues, and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients. GMEB1 overexpression facilitated HCC cell multiplication, migration, and invasion, and suppressed the apoptosis, whereas GMEB1 knockdown had the opposite effects. GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells. CONCLUSION: GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.

Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent malignancy of the digestive tract worldwide, characterized by a significant morbidity and mortality rate and subtle initial symptoms. Diarrhea, local abdominal pain, and hematochezia occur with the development of cancer, while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC. Without timely interventions, the disease can have fatal consequences within a short span. The current therapeutic options for colon cancer include olaparib and bevacizumab, which are widely utilized. This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC, hoping to provide insights into advanced CRC treatment. AIM: To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC. METHODS: A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019. Among them, 43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group, and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group. Subsequent to different treatment regimens, the short-term efficacy, time to progression (TTP), and incidence rate of adverse reactions between the two groups were compared. Changes in serum-related indicators [vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9), cyclooxygenase-2 (COX-2)] and tumor markers [human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199)] levels before and after treatment were compared between the two groups at the same time. RESULTS: The objective response rate was discovered to be 82.05%, and the disease control rate was 97.44% in the observation group, which were significantly higher than the respective rates of 58.14% and 83.72% in the control group (P < 0.05). The median TTP was 24 mo (95%CI: 19.987-28.005) in the control group and 37 mo (95%CI: 30.854-43.870) in the observation group. The TTP in the observation group was significantly better than that in the control group, and the difference held statistical significance (log-rank test value = 5.009, P = 0.025). Before treatment, no substantial difference was detected in serum VEGF, MMP-9, and COX-2 levels and tumor markers HE4, CA125, and CA199 levels between the two groups (P > 0.05). Following treatment with different regimens, the above indicators in the two groups were remarkably promoted (P < 0.05), VEGF, MMP-9, and COX-2 in the observation group were lower than those in the control group (P < 0.05), and HE4, CA125, and CA199 levels were also lower than those in the control group (P < 0.05). Vis-à-vis the control group, the total incidence of gastrointestinal reactions, thrombosis, bone marrow suppression, liver and kidney function injury, and other adverse reactions in the observation group was notably lowered, with the difference considered statistically significant (P < 0.05). CONCLUSION: Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF, MMP-9, COX-2 and tumor markers HE4, CA125 and CA199. Moreover, given its fewer adverse reactions, it can be regarded as a safe and reliable treatment option.

A prospective study of chronic postsurgical pain in elderly patients: incidence, characteristics and risk factors.

BACKGROUND: Due to the continued growth of surgical procedures in older adults and the significant impact of chronic postsurgical pain (CPSP), it is crucial to improve our understanding of the occurrence of CPSP as well as the appropriate prevention and treatment. We therefore conducted this study to determine the incidence, characteristics and risk factors of CPSP in elderly patients at both 3 and 6 months after surgery. METHODS: Elderly patients (aged ≥ 60 years) undergoing elective surgery in our institution between April 2018 and March 2020 were prospectively enrolled in this study. Data on demographics, preoperative psychological well-being, intraoperative surgical and anesthesia management, and acute postoperative pain intensity were collected. At 3 and 6 months after surgery, patients received telephone interview and completed the questionnaires regarding chronic pain characteristics, analgesic consumption, and interference of the pain with activities of daily living (ADL). RESULTS: A total of 1065 elderly patients were followed up for 6 postoperative months and included in final analysis. At 3 and 6 months after operation, the incidence of CPSP was 35.6% [95% confidence interval (95% CI) 32.7 - 38.8%] and 21.5% (95% CI 19.0% - 23.9%), respectively. CPSP cause negative impacts on patient's ADL and most particularly on mood. Neuropathic features were found in 45.1% of the patients with CPSP at 3 months. At 6 months, 31.0% of those with CPSP reported that the pain had neuropathic features. Preoperative anxiety [3 months: Odds ratio (OR) 2.244, 95% CI 1.693 to 2.973; 6 months: OR 2.397, 95% CI 1.745 to 3.294], preoperative depression (3 months: OR 1.709, 95% CI 1.292 to 2.261; 6 months: OR 1.565, 95% CI 1.136-2.156), orthopedic surgery (3 months: OR 1.927, 95% CI 1.112 to 3.341; 6 months: OR 2.484, 95% CI 1.220 to 5.061), higher pain severity on movement within postoperative 24 h (3 months: OR 1.317, 95% CI 1.191 to 1.457; 6 months: OR 1.317, 95% CI 1.177 to 1.475) were associated with a higher risk for CPSP independently at both 3 and 6 months after surgery. CONCLUSIONS: CPSP is a common postoperative complication in elderly surgical patients. Preoperative anxiety and depression, orthopedic surgery, and greater intensity of acute postoperative pain on movement are associated with an increased risk for CPSP. It should be kept in mind that developing psychological interventions to reduce anxiety and depression and optimizing the management of acute postoperative pain will be effective in reducing the development of CPSP in this population.

ATB0,+-targeted nanoparticles initiate autophagy suppression to overcome chemoresistance for enhanced colorectal cancer therapy.

Oxaliplatin (OXA) resistance remains the major obstacle to the successful chemotherapy of colorectal cancer (CRC). As a self-protection mechanism, autophagy may contribute to tumor drug resistance, therefore autophagy suppression could be regarded as a possible treatment option in chemotherapy. Cancer cells, especially drug-resistant tumor cells, increase their demand for specific amino acids by expanding exogenous supply and up-regulating de novo synthesis, to meet the needs for excessive proliferation. Therefore, it is possible to inhibit cancer cell proliferation through pharmacologically blocking the entry of amino acid into cancer cells. SLC6A14 (ATB0,+) is an essential amino acid transporter, that is often abnormally up-regulated in most cancer cells. Herein, in this study, we designed oxaliplatin/berbamine-coloaded, ATB0,+-targeted nanoparticles ((O + B)@Trp-NPs) to therapeutically target SLC6A14 (ATB0,+) and inhibit cancer proliferation. The (O + B)@Trp-NPs utilize the surface-modified tryptophan to achieve SLC6A14-targeted delivery of Berbamine (BBM), a compound that is found in a number of plants used in traditional Chinese medicine, which could suppress autolysosome formation though impairing autophagosome-lysosome fusion. We verified the feasibility of this strategy to overcome the OXA resistance during colorectal cancer treatment. The (O + B)@Trp-NPs significantly inhibited the proliferation and decreased the drug resistance of resistant colorectal cancer cells. In vivo, (O + B)@Trp-NPs greatly suppressed the tumor growth in tumor-bearing mice, which is consistent with the in vitro data. This research offers a unique and promising chemotherapeutic treatment for colorectal cancer.

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

Glutamine-Based Metabolism Normalization and Oxidative Stress Alleviation by Self-Assembled Bilirubin/V9302 Nanoparticles for Psoriasis Treatment.

Psoriasis is an immune-mediated chronic inflammatory skin disorder characterized by epidermal hyperplasia and infiltration of inflammatory cells. Even though the pathogenesis remains unclear, T helper 17 (Th17) cells-mediated inflammation and keratinocyte-involved proliferation are considered to play key roles during the occurrence and the development of psoriasis. Therefore, suppressing the infiltration/function of Th17 and the abnormal hyperplasia of keratinocytes can be a rational strategy for ameliorating and treating psoriasis. In this study, a self-assembly nanoparticle (BVn) is developed with bilirubin (an endogenous antioxidant) and V9302 (a blocker of ASCT2, an amino acid transporter mediating glutamine influx for providing energy and activating mammalian target of rapamycin [mTOR] pathway) to intervene the local metabolism and alleviate oxidative stress for psoriasis treatment. BVn effectively suppresses inflammatory keratinocyte proliferation and scavenges excess reactive oxygen species (ROS). In the in vivo psoriasis mouse model, BVn shows increased permeation and delayed retention in the psoriatic lesion and reverses the psoriasis-related symptoms, evidenced by the normalized keratinocyte condition and decreased Th17 infiltration/activation. Mechanism study indicates that BVn not only cut off the energy supply but also suppressed cell proliferation or lymph cell expansion by deactivating mTOR pathway, besides alleviated oxidative stress. BVn-based glutamine metabolism modulation strategy offers a promising strategy for psoriasis therapy.

Recombinant protein drugs-based intra articular drug delivery systems for osteoarthritis therapy.

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease. It weakens the motor function of patients and imposes a significant economic burden on society. The current medications commonly used in clinical practice do not meet the need for the treatment of OA. Recombinant protein drugs (RPDs) can treat OA by inhibiting inflammatory pathways, regulating catabolism/anabolism, and promoting cartilage repair, thereby showing promise as disease-modifying OA drugs (DMOADs). However, the rapid clearance and short half-life of them in the articular cavity limit their clinical translation. Therefore, the reliable drug delivery systems for extending drug treatment are necessary for the further development. This review introduces RPDs with therapeutic potential for OA, and summarizes their research progress on related drug delivery systems, and make proper discussion on the certain keys for optimal development of this area.

Association of dietary n - 3 polyunsaturated fatty acids with breast cancer risk: Serial mediating roles of erythrocyte n - 3 polyunsaturated fatty acids.

Background: Dietary n - 3 polyunsaturated fatty acids (PUFAs) were found to be inversely associated with breast cancer risk; however, the underlying pathways between them remain uncertain. We aimed to explore serial mediatory roles of erythrocyte n - 3 PUFAs in association between dietary n - 3 PUFAs and breast cancer risk. Materials and methods: Using a case-control study, 850 cases and 861 controls completed structured questionnaires with dietary information. Erythrocyte n - 3 PUFAs were measured by gas chromatography. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multiple unconditional logistic regression models to examine association between dietary n - 3 PUFAs and breast cancer risk. Mediation analyses with bootstrapping were conducted to investigate indirect effects. Results: Higher intake of dietary ALA, long-chain n - 3 PUFAs and total n - 3 PUFAs was associated with lower risk of breast cancer. The adjusted OR tertile 3 v.1 (95% CI) was 0.70 (0.55, 0.90) for ALA, 0.76 (0.60, 0.97) for long-chain n - 3 PUFAs and 0.74 (0.58, 0.94) for total n - 3 PUFAs, respectively. Mediation analysis showed that erythrocyte long-chain n - 3 PUFAs served as sequential mediators in the relationship between dietary long-chain or total n - 3 PUFAs and breast cancer risk. In particular, erythrocyte long-chain n - 3 PUFAs completely mediated the association between dietary long-chain n - 3 PUFAs and breast cancer risk [indirect effect (95% CI) = -0.982 (-1.529, -0.508)]. The relationship between dietary total n - 3 PUFAs and breast cancer risk was partly mediated by erythrocyte long-chain n - 3 PUFAs [indirect effect (95% CI) = -0.107 (-0.216, -0.014)], accounting for 19.31%. However, the serial mediation model in dietary ALA and risk of breast cancer was not statistically significant [indirect effect (95% CI) = -0.042 (-0.144, 0.049)]. Conclusion: This study highlights the complexity and inaccuracy in using a simple analysis of individual dietary n - 3 PUFAs to examine their associations with breast cancer risk without considering the variety of metabolic processes. Interventions aimed at increasing erythrocyte long-chain n - 3 PUFAs may represent a promising strategy for breast cancer prevention.

Case Report: Anesthesia for Cesarean Section in Parturients With Chronic Renal Failure Requiring Hemodialysis: Case Reports and Literature Review.

Pregnancies are rare in women with chronic renal failure requiring hemodialysis. Although a chance of successful pregnancy and delivery in hemodialysis women has increased over the years, it is still very low, and with high maternal and fetal mortality and morbidity rate compared to normal population. And cesarean section is usually used for delivery. The first case was a 32-year-old Chinese woman with chronic kidney disease stage V undergoing maintenance hemodialysis for six years. The second case was also a 32-year-old patient with a 6-year history of hemodialysis for chronic glomerulonephritis. And due to a history of atrial septal defect and hypertension she received intensive hemodialysis during pregnancy. Both cases were scheduled for cesarean delivery under epidural anesthesia. To help develop reasonable anesthetic methods and management objectives for such patients, we described our anesthetic management and performed a literature search on published cases of cesarean section with chronic renal failure undergoing hemodialysis.

Cost-Effectiveness Analysis of Molnupiravir Versus Best Supportive Care for the Treatment of Outpatient COVID-19 in Adults in the US.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) imposes a substantial and ongoing burden on the US healthcare system and society. Molnupiravir is a new oral antiviral for treating COVID-19 in outpatient settings. This study evaluated the cost-effectiveness profile of molnupiravir versus best supportive care in the treatment of adult patients with mild-to-moderate COVID-19 at risk of progression to severe disease, from a US payer's perspective. METHODS: The model was developed using a decision tree for the short-term acute phase of COVID-19 and a Markov state transition model for the long-term post-acute phase. This model compared molnupiravir with best supportive care as consistent with the MOVe-OUT trial. Costs were reported in 2021 US dollars. Transition probabilities were derived from the phase III MOVe-OUT trial and the TriNetX real-world electronic health records database. Costs were derived from the TriNetX database and utility values from a de novo, vignette-based utility study. Deterministic and probabilistic sensitivity analyses (DSA/PSA) were conducted. Primary outcomes included proportion hospitalized, proportion who died overall and by highest healthcare setting at the end of the acute phase, quality-adjusted life-years (QALYs), and incremental costs per QALY gained over a lifetime (100 years) horizon, discounted at 3% annually and assessed at a willingness-to-pay (WTP) threshold of $100,000 per QALY. RESULTS: In this model, the use of molnupiravir led to an increase in QALYs (0.210) and decrease in direct total medical costs (-$895) per patient across a lifetime horizon, compared with best supportive care in COVID-19 outpatients. Molnupiravir was the dominant intervention when compared with best supportive care. Patients treated with molnupiravir were less likely to be hospitalized (6.38% vs. 9.20%) and more likely to remain alive (99.88% vs. 98.71%) during the acute phase. Through DSA, molnupiravir treatment effect of hospitalization reduction was identified to be the most influential parameter, and through PSA, molnupiravir remained dominant in 84% of the total simulations and, overall, 100% cost effective. CONCLUSION: This analysis suggests that molnupiravir is cost effective compared with best supportive care for the treatment of adult outpatients with COVID-19. However, our study was limited by the unavailability of the most recent information on the rapidly evolving pandemic, including new viral variants, patient populations affected, and changes in standards of care. Further research should explore the impact of vaccination on the cost effectiveness of molnupiravir and other therapies, based on real-world data, to account for these changes, including the impact of vaccination and immunity.