Financial toxicity experienced by patients with breast cancer-related lymphedema: a systematic review.

PURPOSE: To perform a systematic review on financial toxicity of breast cancer-related lymphedema. METHODS: Seven databases were searched on September 11, 2022. Eligible studies were identified, analyzed, and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Empirical studies were appraised by the Joanna Briggs Institute (JBI) tools. The Mixed Methods Appraisal Tool version 2018 was used to assess the mixed method studies. RESULTS: A total of 963 articles were identified, but only 7 articles reporting on 6 studies met the eligibility criteria. A 2-year treatment for lymphedema was approximately USD$14,877 to USD$23,167 in America. In Australia, the average out-of-pocket costs ranged from A$207 to A$1400 (USD$156.26 to USD$1056.83) per year. Outpatient visits, compressed clothing, and hospital admissions were the dominant costs. The financial toxicity was associated with the severity of lymphedema, and patients with heavy financial burden had to reduce other expenses or even forgo the treatment. CONCLUSION: Breast cancer-related lymphedema aggravated the economic burden of patients. The included studies showed great variation in the methods used and therefore differences in cost results. The national government should further improve the healthcare system and increase the insurance coverage of lymphedema treatment to alleviate this burden. More research is needed to focus on financial toxicity experience of breast cancer patients with lymphedema. IMPLICATIONS FOR CANCER SURVIVORS: The cost of the ongoing treatment of breast cancer-related lymphedema influences patients' economic situation and quality of life. Survivors need to be informed early about the potential financial burden associated with lymphedema treatment.

Base-Promoted Decarboxylative Annulation of Methyl 2-(2-Bromophenyl)acetates and Ynones to Access Benzoxepines.

A simple and efficient base-mediated decarboxylative annulation of ynones with methyl 2-(2-bromophenyl)acetates has been developed. A broad range of benzoxepines were prepared with a broad substrate scope and high regioselectivity in moderate to excellent yields under transition-metal-free conditions. This method proceeds through a tandem [2 + 4] annulation, ring-opening decarboxylative reaction, and the intramolecular nucleophilic aromatic substitution reaction. Additionally, the key intermediates were successfully obtained and characterized unambiguously by single-crystal X-ray crystallography, which could favorably support a decarboxylative annulation mechanism. Furthermore, gram-scale reaction and synthetic applications for the further functionalization are also studied.

Base-Promoted Divergent Annulation of Conjugated Ynones and Methyl 2-(Cyanomethyl)benzoates to Access 1-Naphthols and Xanthones.

A facile and efficient base-mediated divergent annulation of methyl 2-(cyanomethyl)benzoates and conjugated ynones has been described. A broad range of 1-naphthols and xanthones were formed in moderate to excellent yields. The notable features of this protocol include readily available precursors, broad substrate scope, complete regioselectivity, and substrate-controlled divergent synthesis. The gram-scale preparation and synthetic transformations of the resulting 1-naphthols and xanthones demonstrate their utility.

AKR1C3 regulated by NRF2/MAFG complex promotes proliferation via stabilizing PARP1 in hepatocellular carcinoma.

Aldo-keto reductase family 1 member C3 (AKR1C3) serves as a contributor to numerous kinds of tumors, and its expression is elevated in patients with hepatocellular carcinoma (HCC). However, the biological function of AKR1C3 in HCC remains unclear. Here we investigated the role of AKR1C3 in liver carcinogenesis using in vitro and in vivo models. We determined that AKR1C3 is frequently increased in HCC tissues with poor prognosis. Genetically manipulated cells with AKR1C3 construction were examined to highlight the pro-tumoral growth of both wild-type AKR1C3 and mutant in vitro and in vivo. We observed promising treatment effects of AKR1C3 shRNA by intratumoral injection in mice. Mechanically, we demonstrated that the transcription factor heterodimer NRF2/MAFG was able to bind directly to AKR1C3 promoter to activate its transcription. Further, AKR1C3 stabilized PARP1 by decreasing its ubiquitination, which resulted in HCC cell proliferation and low sensitivity of Cisplatin. Moreover, we discovered that the tumorigenic role of AKR1C3 was non-catalytic dependent and the NRF2/MAFG-AKR1C3-PARP1 axis might be one of the important proliferation pathways in HCC. In conclusion, blockage of AKR1C3 expression provides potential therapeutic benefits against HCC.

Airway malacia in premature infant twins with bronchopulmonary dysplasia: Two case reports.

Premature infants who require surgery for retinopathy of prematurity often exhibit bronchopulmonary dysplasia. Reactive airway is a clinical manifestation of bronchopulmonary dysplasia. We describe premature infant twins who had difficulty with positive pressure ventilation during anesthesia. Both cases occurred during induction of anesthesia for binocular anterior chamber puncture and vitreous cavity injection. The most likely cause in each case was airway malacia. We recommend that endotracheal intubation is performed in infant patients with low body weight; the possibility of airway malacia occurrence should be considered, especially for infants with comorbid bronchopulmonary dysplasia.

Internet Development, Consumption Upgrading and Carbon Emissions-An Empirical Study from China.

Internet development has changed Chinese people's consumption behavior, gradually expanding from survival consumption (SC) to development and enjoyment consumption (DEC) trends. Consumption is the new engine driving China's economic growth and the terminal of carbon emissions. Simultaneously, China is undergoing a profound change toward the "double carbon" goal, the space for carbon emission reduction in traditional fields is gradually compressed. Therefore, it is necessary to explore carbon emissions from the perspective of consumption terminals. Based on provincial panel data, we use the fixed effects model and mediating effects model to explore the relationship between Internet development, consumption upgrading, and carbon emissions in a unified research framework. The findings show that: (1) Internet development leads to an increase in carbon emissions. A finding remains significant after using instrumental variables to mitigate endogeneity; (2) Internet development promotes consumption upgrading, reflected in development and enjoyment consumption expenditure; (3) Internet development contributes to increasing carbon emissions through consumption upgrading. Heterogeneity analysis shows that Internet development in eastern China significantly contributes to carbon emissions through consumption upgrading, while it is insignificant in central and western regions. The Internet development leading region contributes to an increase in carbon emissions through consumption upgrading. In comparison, the lagging region is insignificant. This study can provide a reference for policymakers in China or other countries to formulate energy-saving and emission-reduction policies in the Internet industry and provide a scientific basis for advocating people's low-carbon consumption behavior and achieving carbon emission reduction at the consumption terminal.

Phosphine-Catalyzed Synthesis of 3-Allyl-4-pyrones by the Tandem Reaction of Diynones and Allylic Alcohols.

A simple and effective tandem reaction of diynones and allylic alcohols was developed to afford functionalized 3-allyl-4-pyrones in moderate to excellent yields. This protocol underwent a Michael addition─Claisen rearrangement─O-cyclization process, which exhibited broad substrate tolerance, high regioselectivity, and atom economy under a metal-free condition. Moreover, functional transformation of the products was also further studied.

AKR1C3 decreased CML sensitivity to Imatinib in bone marrow microenvironment via dysregulation of miR-379-5p.

BACKGROUND: Drug resistance is an important cause of death for most patients with chronic myeloid leukemia (CML). The bone marrow microenvironment is believed to be mainly responsible for resistance to BCR-ABL tyrosine kinase inhibitors. The mechanism involved, however, is still unclear. METHODS: Bioinformatic analysis from GEO database of AKR1C3 was utilized to identify the AKR1C3 expression in CML cells under bone marrow microenvironment. Western blot and qPCR were performed to detect the AKR1C3 expression in two CML cell lines K562 and KU812 cultured +/- bone microenvironment derived stromal cells. CCK-8, soft agar colony assay, and Annexin V/PI assay were performed to detect the sensitivity of CML cells (K562 and KU812) to Imatinib under a gain of or loss of function of AKR1C3 treatment. The CML murine model intravenous inoculated with K562-OE-vector and K562-OE-AKR1C3 cells were established to estimate the effect of AKR1C3 inhibitor Indomethacin on Imatinib resistance. The bioinformatic analysis of miRNA databases was used to predict the potential miRNAs targeting AKR1C3. And the luciferase assay was utilized to validate the target relationship between miR-379-5p and AKR1C3. And, the soft agar colony assay and Annexin V/PI were used to validate the effect of miR-379-5p in AKR1C3 induced Imatinib resistance. RESULTS: In present study, we investigated AKR1C3 was highly expressed in CML under bone marrow microenvironment. AKR1C3 decreased Imatinib activity in K562 and KU812 cells, while inhibition of AKR1C3 could enhance Imatinib sensitivity in vitro study. Furthermore, murine model results showed combination use of AKR1C3 inhibitor Indomethacin effectively prolong mice survival, indicating that AKR1C3 is a promising target to enhance Imatinib treatment. Mechanically, AKR1C3 was found to be suppressed by miR-379-5p, which was down-expression in bone marrow microenvironment. Besides, we found miR-379-5p could bind AKR1C3 3'UTR but not degrade its mRNA level. Further, gain of miR-379-5p rescued the imatinib resistance induced by AKR1C3 overexpression in CML cells. CONCLUSIONS: Altogether, our study identifies a novel signaling regulation of miR-379-5p/AKR1C3/EKR axis in regulating IM resistance in CML cell, and provides a scientific base for exploring AKR1C3 as a biomarker in impeding IM resistance in CML.

Catalyst- and Additive-Free Annulation of Ynediones and (Iso)Quinoline N-Oxides: An Approach to Synthesis of Pyrrolo[2,1-a]Isoquinolines and Pyrrolo[1,2-a]Quinolines.

A simple and effective annulation of ynediones and (iso)quinoline N-oxides was developed to afford various functionalized pyrrolo[2,1-a]isoquinolines and pyrrolo[1,2-a]quinolines in moderate to excellent yields. This protocol underwent a tandem [3 + 2] cycloaddition/ring-opening/N-nucleophilic addition, which exhibited high regioselectivity, broad substrate tolerance, and atom economy under catalyst-, additive-free, and air conditions. Moreover, indolizine was also successfully prepared using pyridine N-oxide.

miR-203a suppresses cell proliferation by targeting RING-finger protein 6 in colorectal cancer.

Colorectal cancer (CRC) is one of most common cancers worldwide. Although miR-203a is reported as a tumor suppressor involved in cell progression in some cancers, the role of miR-203a in CRC is still controversial and the underling mechanism of miR-203a in CRC remains unclear. Here, we demonstrated that low expression of miR-203a had poorer survival in CRC patients. miR-203a was down-regulated in most human colon cancer cells. Overexpression of miR-203a could inhibit colon cancer cell proliferation and arrest cell cycle in G1 phase. Bioinformatics and dual luciferase reporter assay confirmed that RING-finger protein 6 (RNF6) was a target gene of miR-203a. Silencing RNF6 inhibited cell proliferation and arrest cell cycle in G1 phase. RNF6 overexpression reversed the effects of miR-203a overexpression in colon cancer cells. Taken together, our data indicate that miR-203a inhibits colon cancer cell proliferation by targeting RNF6, offer novel insights into the regulatory network of miR-203a-modulated cell cycle and proliferation, and suggest that miR-203a a potential therapeutic target in CRC treatment.

Solvent-controlled divergent annulation of ynones and (iso)quinoline N-oxides: of 3-((iso)quinolin-1-yl)-4H-chromen-4-ones and 13H-isoquinolino[2,1-a]quinolin-13-ones.

An effective annulation of ynones and (iso)quinoline N-oxides was developed to deliver various functionalized 3-((iso)quinolin-1-yl)-4H-chromen-4-ones and 13H-isoquinolino[2,1-a]quinolin-13-ones in moderate to excellent yields, respectively. This protocol exhibits high regioselectivity and broad substrate scope under transition-metal-free conditions. Moreover, the key reaction intermediate was successfully isolated and determined unambiguously by single crystal X-ray crystallography.

Calculation of Volume Fractions of In Situ TiB and Residual Stress Distributions in Functionally Graded Composite of Ti-TiB-TiB2.

Ti matrix composite with a polylaminate structure was successfully fabricated via spark plasma sintering (SPS) process. A temperature gradient field (TGF) was obtained during the sintering to form functionally graded material (FGM) in a vacuum under 40 MPa for 5 min. The actual volume fractions of TiB in the matrix were calculated based on the X-ray diffraction pattern. The target volume fractions of TiB were 0%, 20%, 40%, 60%, 80% and 100%. The calculated TiB volume fractions were slightly higher than the target volume fractions in layers 2-4 and lower than the target volume fractions in layers 5-6 and the deviations in layers 4 and 5 were less than 5% of the target volume. Based on the elastic axial symmetry model, the residual stress distributions in the Ti matrix composite with a polylaminate structure were simulated, indicating a relatively low thermal residual stress in the FGM.

Controllable synthesis of 3-iodo-2H-quinolizin-2-ones and 1,3-diiodo-2H-quinolizin-2-ones via electrophilic cyclization of azacyclic ynones.

An effective electrophilic annulation reaction of azacyclic ynones was reported, divergently affording various functionalized 3-iodo-2H-quinolizin-2-ones and 1,3-diiodo-2H-quinolizin-2-ones in moderate to excellent yields with different iodide reagents. This reaction shows high regioselectivity and broad substrate scope under metal-free, room temperature conditions in air. In addition, the products with highly active C-I bonds have an opportunity for further functionalization.

Base-Controlled Divergent Synthesis of 5-Cyanobenzoxepines and Benzofuro[2,3-b]pyridines from 2-Bromophenylacetonitriles and Ynones.

An effective base-controlled divergent annulation reaction of 2-bromophenylacetonitriles and ynones has been developed. Various functionalized 5-cyanobenzoxepines and benzofuro[2,3-b]pyridines were obtained with a broad substrate scope and high regioselectivity in moderate to excellent yield. Of importance, an unexpected O-rearrangement reaction to access benzofuro[2,3-b]pyridines was observed using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base, and the possible mechanism was supported by 18O-labeled experiments. In addition, the gram-scale synthesis and further transformation of the product were studied.

An efficient tandem synthesis of chromones from o-bromoaryl ynones and benzaldehyde oxime.

An effective transition-metal-free strategy was developed for the preparation of chromones from o-bromoaryl ynones and benzaldehyde oxime through sequential C-O bond formation. This cyclization reaction could well tolerate a wide range of functional groups, and the corresponding chromones were given in moderate to excellent yields. Mechanistically, benzaldehyde oxime as a hydroxide source and 1,3-diketone derivatives as reaction intermediates were involved in this transformation.

Synthesis of 1-Cyano-3-acylnaphthalenes via Formal [4+2] Benzannulation of 2-(2-Alkynylphenyl)acetonitriles and Alkynones.

Effective transition-metal-free formal [4+2] benzannulation for the preparation of 1-cyano-3-acylnaphthalenes from 2-(2-alkynylphenyl)acetonitriles and alkynones through sequential C-C bond coupling has been developed. This protocol is characterized by mild conditions, excellent functional group tolerance, complete regioselectivity, and atom economy. The plausible mechanism, gram-scale synthesis, and further transformations of the product were studied.

An efficient preparation of ß-ketophosphine oxides from alkynylphosphine oxides with benzaldehyde oxime as a hydroxide source.

An effective and facile transition-metal-free method has been developed for the synthesis of ß-ketophosphine oxides from alkynylphosphine oxides with benzaldehyde oxime as a hydroxide surrogate. The current methodology provides simple access to various ß-ketophosphine oxides in moderate to excellent yields with a broad substrate scope.

Prevention of cisplatin-induced hearing loss by extended release fluticasone propionate intracochlear implants.

OBJECTIVE: Cisplatin is a chemotherapeutic drug known to induce hearing loss. Although corticosteroids may help to mitigate the ototoxic side effects of cisplatin, there are complications associated with their systemic and prolonged use. The goal of this study is to test the efficacy of extended-release fluticasone propionate intracochlear implant particles to protect against cisplatin-induced hearing loss. METHODS: We used guinea pigs (n = 9) injected with cisplatin (IP, 12 mg/kg weight). Fluticasone particles were delivered to the cochlear scala tympani through the round window membrane into the right ears of the guinea pigs (left ears being used as a control) two weeks prior to cisplatin administration, and hearing function was evaluated by ABR and DPOAE before implantation, immediately before cisplatin administration, and 2 weeks after the challenge with cisplatin. Data was statistically evaluated using paired t-test analysis. RESULTS: No significant differences were observed in ABR threshold between control and implanted ears on day 14 (23.9 ±â€¯2.3 dB vs. 25.6 ±â€¯1.3 dB, P = 0.524), whereas the significant cisplatin-induced hearing loss in control animals (23.9 ±â€¯2.3 dB at day 14 vs. 40.7 ±â€¯2.5 dB at day 28, P ≤ 0.0001) was prevented in implanted animals (25.6 ±â€¯1.3 dB at day 14 vs. 25.0 ±â€¯3.1 at day 28, P ≥ 0.85). A similar, though not statistically significant, trend was observed in DPOAE responses in untreated ears (7.9 ±â€¯5.8 dB at day14 vs. -0.5 ±â€¯5.3 dB at day 28, P = 0.654) as compared to treatment (11.1 ±â€¯3.4 dB at day 14 vs. 13.6 ±â€¯4.8 dB at day 28, P = 0.733). CONCLUSION: These results suggest that fluticasone intracochlear implants are safe and able to provide effective otoprotection against cisplatin-induced hearing loss in the guinea pig model.

Combined administration of a sedative dose sevoflurane and 60% oxygen reduces inflammatory responses to sepsis in animals and in human PMBCs.

Our study aims to investigate the effects of the inhalation of subanesthestic doses of sevoflurane combined with oxygen on sepsis. Male Sprague-Dawley rats or Male ICR/Km mice underwent caecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysccharide (LPS) to induce sepsis, while sham rats were used as control. Then, rats were treated with the inhalation of sevoflurane in oxygen; and air or 100% oxygen was used as control. Seven-day survival, lung injury and inflammatory factors were assessed. In this in vitro experiment, we obtained RAW264.7 macrophages and human peripheral blood mononuclear cells (PBMCs) incubated by LPS or plasma from septic patients to explore the NF-κB pathway in the effect of the inhalation of sevoflurane combined with oxygen in sepsis. In this study, we found that the inhalation of 0.5 MAC of sevoflurane in 60% oxygen was the best protocol for protecting against lethality resulting from sepsis and ALI, and there was a time window for these protective effects. We also founded that 0.5 MAC of sevoflurane in 60% oxygen inhibited the nuclear translocation of NF-κB in human PBMCs induced by LPS or plasma from septic patients. The subanesthesia dose sevoflurane in 60% oxygen may reduce sepsis-induced inflammatory responses in animals and in PBMCs, and the inhibition to the activation of the NF-κB pathway may contribute to this protection.

Sub-anesthesia Dose of Isoflurane in 60% Oxygen Reduces Inflammatory Responses in Experimental Sepsis Models.

BACKGROUND: Sepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial in sepsis; however, their application in septic patients is limited because long-term hyperoxia may induce oxygen toxicity and anesthetic dose isoflurane has potential adverse consequences. This study was scheduled to find the optimal combination of isoflurane and oxygen in protecting experimental sepsis and its mechanisms. METHODS: The effects of combined therapy with isoflurane and oxygen on lung injury and sepsis were determined in animal models of sepsis induced by cecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysaccharide (LPS) or zymosan. Mouse RAW264.7 cells or human peripheral blood mononuclear cells (PBMCs) were treated by LPS to probe mechanisms. The nuclear factor kappa B (NF-κB) signaling molecules were examined by Western blot and cellular immunohistochemistry. RESULTS: The 0.5 minimum alveolar concentration (MAC) isoflurane in 60% oxygen was the best combination of oxygen and isoflurane for reducing mortality in experimental sepsis induced by CLP, intraperitoneal injection of LPS, or zymosan. The 0.5 MAC isoflurane in 60% oxygen inhibited proinflammatory cytokines in peritoneal lavage fluids (tumor necrosis factor-alpha [TNF-ß]: 149.3 vs. 229.7 pg/ml, interleukin [IL]-1ß: 12.5 vs. 20.6 pg/ml, IL-6: 86.1 vs. 116.1 pg/ml, and high-mobility group protein 1 [HMGB1]: 323.7 vs. 449.3 ng/ml; all P< 0.05) and serum (TNF-ß: 302.7 vs. 450.7 pg/ml, IL-1ß: 51.7 vs. 96.7 pg/ml, IL-6: 390.4 vs. 722.5 pg/ml, and HMGB1: 592.2 vs. 985.4 ng/ml; all P< 0.05) in septic animals. In vitro experiments showed that the 0.5 MAC isoflurane in 60% oxygen reduced inflammatory responses in mouse RAW264.7 cells, after LPS stimulation (all P< 0.05). Suppressed activation of NF-κB pathway was also observed in mouse RAW264.7 macrophages and human PBMCs after LPS stimulation or plasma from septic patients. The 0.5 MAC isoflurane in 60% oxygen also prevented the increases of phospho-IKKß/ß, phospho-IκBß, and phospho-p65 expressions in RAW264.7 macrophages after LPS stimulation (all P< 0.05). CONCLUSION: Combined administration of a sedative dose of isoflurane with 60% oxygen improves survival of septic animals through reducing inflammatory responses.