Postoperative outcomes of minimally invasive versus conventional nipple-sparing mastectomy with prosthesis breast reconstruction in breast cancer: a meta-analysis.

Breast cancer is the most common malignant tumor worldwide, and mastectomy remains the primary strategy for treating early stage breast cancer. However, the complication rates, surgical variables, and oncologic safety of minimally invasive nipple-sparing mastectomy (MINSM) have not been fully addressed. We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for randomized-controlled trials (RCTs) and non-RCTs that compared MINSM with conventional nipple-sparing mastectomy (CNSM), both followed by Prosthesis Breast Reconstruction (PBR). The main outcomes observed included overall complications, (Grade III) complications, skin and nipple necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, and oncologic safety (positive margins and recurrence). Secondary outcomes included operation time, blood loss, hospital stay, cost-effectiveness, and patient satisfaction. Binary and continuous variables were compared using odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). A total of 10 studies involving 2,166 patients were included. There were no statistically significant differences between MINSM and CNSM in terms of skin necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, or oncologic safety. However, MINSM significantly reduced overall complications (OR = 0. 74, 95% CI [0. 58, 0. 94], p = 0. 01) and (Grade III) complications (OR = 0. 47, 95% CI [0. 31, 0. 71], p = 0. 0003). Nipple necrosis events were also significantly reduced in the MINSM group (OR = 0. 49, 95% CI [0. 30, 0. 80], p = 0. 005). Patient satisfaction improved notably in the MINSM group. Additionally, compared with the CNSM group, the MINSM group had longer operating times (MD = 46. 88, 95% CI [19. 55, 74. 21], p = 0. 0008) and hospital stays (MD = 1. 39, 95% CI [0. 65, 2. 12], p < 0. 001), while intraoperative blood loss was significantly reduced (MD = -29. 05, 95% CI [-36. 20, -21. 90], p < 0. 001). Compared with CNSM, MINSM offers advantages in reducing complications and intraoperative blood loss, as well as improving aesthetic outcomes and patient satisfaction. Therefore, MINSM may become a viable option for breast surgery. Nevertheless, a long-term evaluation of the oncologic safety of this approach is necessary to ensure its efficacy and safety for patients.

Association between Copper Exposure and Cognitive Function: A Cross-Sectional Study in a County, Guangxi, China.

There has been growing attention to the impact of copper exposure on cognitive function; however, current research on the specific information regarding urinary copper and cognitive function is limited, particularly detailed analyses in the Chinese adult population. This study aimed to explore the association between copper exposure and cognitive function in a cross-sectional design. A total of 2617 participants in a county, Guangxi Zhuang Autonomous Region (Guangxi), China, were included. The mini-mental state examination (MMSE) was used to assess cognitive function, and inductively coupled plasma mass spectrometry was used to measure urinary metal levels. Spearman's rank correlation was used to analyze the correlation between urinary copper levels and various cognitive function assessment indices. After adjusting for potential confounders, binary logistic regression was used to explore the association between urinary copper levels and the risk of cognitive impairment (CI) as revealed by MMSE, and restricted cubic spline regression was further used to explore the dose-response relationship. The results showed a negative correlation between urinary copper levels and orientation, attention and calculation, memory, language ability, and MMSE total scores (P < 0.05). Compared with the low copper exposure group, the high exposure group showed a 58.5% increased risk of CI (OR = 1.585, 95%CI: 1.125 to 2.235, P = 0.008). A significant linear dose-response relationship was observed between urinary copper levels and the risk of CI (P overall = 0.045, P nonlinearity = 0.081). Our findings suggest that higher copper exposure may be associated with CI in the population of a county, Guangxi, China.

Breast-conserving surgery versus modified radical mastectomy in T1-2N3M0 stage breast cancer: a propensity score matching analysis.

PURPOSE: Breast-conserving surgery (BCS) plus radiotherapy and mastectomy exhibit highly comparable prognoses for early-stage breast cancer; however, the safety of BCS for T1-2N3M0 breast cancer remains unclear. This study compared long-term survival for BCS versus (vs.) modified radical mastectomy (MRM) among patients with T1-2N3M0 breast cancer. METHODS: Data of patients with T1-2N3M0 breast cancer were extracted from the Surveillance, Epidemiology, and End Results database. Eligible patients were divided into 2 groups, BCS and MRM; Pearson's chi-squared test was used to estimate differences in clinicopathological features. Propensity score matching (PSM) was used to balance baseline characteristics. Univariate and multivariate analyses were performed to investigate the effects of surgical methods and other factors on breast cancer-specific survival (BCSS) and overall survival (OS). RESULTS: In total, 2124 patients were included; after PSM, 596 patients were allocated to each group. BCS exhibited the same 5-year BCSS (77.9% vs. 77.7%; P = 0.814) and OS (76.1% vs. 74.6%; P = 0.862) as MRM in the matched cohorts. Multivariate survival analysis revealed that BCS had the same BCSS and OS as MRM (hazard ratios [HR] 0.899 [95% confidence intervals (CI) 0.697-1.160], P = 0.413 and HR 0.858 [95% CI 0.675-1.089], P = 0.208, respectively); this was also seen in most subgroups. BCS demonstrated better BCSS (HR 0.558 [95% CI 0.335-0.929]; P = 0.025) and OS (HR 0.605 [95% CI 0.377-0.972]; P = 0.038) than MRM in those with the triple-negative subtype. CONCLUSIONS: BCS has the same long-term survival as MRM in T1-2N3M0 breast cancer and may be a better choice for triple-negative breast cancer.

Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes. METHODS: A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation. RESULTS: Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4. CONCLUSION: Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.

Genomic alteration discordance in the paired primary-recurrent ovarian cancers: based on the comprehensive genomic profiling (CGP) analysis.

PURPOSE: Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status. MATERIALS AND METHODS: A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOne®CDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors. RESULTS: By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r2 = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways (p < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6. CONCLUSION: The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.

Mechanism of Zhenwu Decoction modulating TLR4/NF-κB/HIF-1α loop through miR-451 to delay renal fibrosis in type 2 CRS.

BACKGROUND: Type 2 cardiorenal syndrome (CRS) is a progressive renal insufficiency in patients with chronic heart failure, but its pathophysiology is still unclear. The Chinese medicine Zhenwu Decoction plays an important role in the prevention and treatment of 2-CRS, however, its mechanism of action remains unknown. PURPOSE: The aim of this study was to investigate whether the ameliorative effect of ZWD on 2-CRS renal fibrosis is related to the modulation of miR-451 expression and thus mediating the TLR4/NF-κB/HIF-1α loop. STUDY DESIGN AND METHODS: A type 2 CRS rat model was constructed using ligation of the left anterior descending branch of the coronary artery + 3/4 nephrectomy, and randomly divided into Control, Sham, Model, Captopril, ZWD-L, ZWD-M and ZWD-H groups.After 4 weeks of ZWD intervention, its effects on cardiac and renal functions of type 2 CRS rats were observed by hematuria and cardiac ultrasonography. Changes in kidney tissue morphology were observed by HE, Masson and PASM staining. The protein and mRNA expression of TLR4, NF-κB, HIF-1α and IκBα in kidney tissues were detected by immunohistochemistry and qPCR. Immunofluorescence was used to detect the protein expression of NF-κB and HIF-1α in renal tissues. Western blot and qPCR were used to detect the protein expression of MCP-1, ICAM-1, IL-1ß, IL-6, TGF-ß, α-SMA, FN, Smad2, Smad3, and E-cadherin in renal tissues. PCR was used to detect the protein expression of miR-451mRNA expression level in kidney tissues. RESULTS: In this study, we found that ZWD was able to reduce the expression of Scr, BUN, NT-proBNP, and 24-hour quantitative urine protein, elevate LVEF, FS, CO, and reduce the level of LVIDS in type 2 CRS rats, as well as attenuate renal interstitial fibrosis and improve tubular swelling. In addition, Zhenwu Decoction up-regulated the expression of miR-451 in renal tissues and inhibited the expression of TLR4, NF-κB, and HIF-1α proteins and genes, which in turn inhibited the expression of inflammatory factors and fibrosis-related factors. CONCLUSION: ZWD was able to up-regulate the expression of miR-451 in renal tissues, inhibit the TLR4/NF-κB/HIF-1α response loop, and then inhibit the expression of inflammatory factors and fibrosis-related factors, improve renal fibrosis, and delay the pathological process of type 2 CRS.

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

BACKGROUND: With the future epidemiology and evolution of SARS-CoV-2 uncertain, use of safe and effective COVID-19 vaccines in pediatric populations remains important. METHODS: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month-<12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month-<5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5-<12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. RESULTS: In 6-month-<5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5-<12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable to dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6 month-<12-year-olds. Reactogenicity events were generally mild-to-moderate. No adverse events led to discontinuation. CONCLUSIONS: These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.

INTRODUCTION: To investigate the role of a novel type of protein kinase C delta (PKCδ) in the neuroinflammation of Alzheimer's disease (AD). METHODS: We analyzed PKCδ and inflammatory cytokines levels in cerebrospinal fluid (CSF) of AD and normal controls, as well as their correlations. The cellular expression pattern of PKCδ and the effects of PKCδ modulation on microglia-mediated neuroinflammation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, RNA sequencing (RNA-seq), and immunofluorescence staining. RESULTS: PKCδ levels were increased dramatically in the CSF of AD patients and positively correlated with cytokines. PKCδ is expressed mainly in microglia in the brain. Amyloid beta (Aß) stimulation increased PKCδ expression and secretion, which led to upregulation of the nuclear factor kappa B (NF-κB) pathway and overproduction of proinflammatory cytokines. Downregulation or inhibition of PKCδ attenuated Aß-induced microglial responses and improved cognitive function in an AD mouse model. DISCUSSION: Our study identifies PKCδ as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD. HIGHLIGHTS: Protein kinase C delta (PKCδ) levels increase in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), and positively correlate with elevated inflammatory cytokines in human subjects. PKCδ is expressed mainly in microglia in vivo, whereas amyloid beta (Aß) stimulation increases PKCδ expression and secretion, causing upregulation of the nuclear factor kappa B (NF-κB) pathway and production of inflammatory cytokines. Downregulation or inhibition of PKCδ attenuates Aß-enhanced NF-κB signaling and cytokine production in microglia and improves cognitive function in AD mice. PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD.

The Identification and Gene Mapping of Spotted Leaf Mutant spl43 in Rice.

Our study investigates the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the spl43 mutant. This mutant is characterized by persistent reddish-brown leaf spots from the seedling stage to maturity, leading to extensive leaf necrosis. Using map-based cloning, we localized the responsible locus to a 330 Kb region on chromosome 2. We identified LOC_Os02g56000, named OsRPT5A, as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and the generation of CRISPR/Cas9-mediated knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. The qPCR results from different parts of the rice plant revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by the mutation. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in spl43 mutants by examining the physiological indexes of leaves, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the spl43 mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice pathogen resistance mechanisms. Overall, our results suggest that OsRPT5A plays a critical role in regulating ROS homeostasis and enhancing pathogen resistance in rice.

Artificial Mitochondria Nanoarchitectonics via a Supramolecular Assembled Microreactor Covered by ATP Synthase.

Abiotic stress tends to induce oxidative damage to enzymes and organelles that in turns hampers the phosphorylation process and decreases the adenosine triphosphate (ATP) productivity. Artificial assemblies can alleviate abiotic stress and simultaneously provide nutrients to diminish the oxidative damage. Here, we have integrated natural acid phosphatase (ACP) and ATP synthase with plasmonic Au clusters in a biomimetic microreactor. ACP immobilized on the Au clusters is harnessed to generate proton influx to drive ATP synthase and concurrently supply phosphate to improve phosphorus availability to combat phosphorus-deficiency stress. In tandem with the reactive oxygen species (ROS) scavenging and the photothermal functionality of Au clusters, such an assembled microreactor exhibits an improved abiotic stress tolerance and achieves plasmon-accelerated ATP synthesis. This innovative approach offers an effective route to enhance the stress resistance of ATP synthase-based energy-generating systems, opening an exciting potential of these systems for biomimicking applications.

Visible light driven photoredox/nickel-catalyzed stereoselective synthesis of Z- or E-vinyl thioethers from thiosilane and terminal alkynes.

A new method for the synthesis of anti-Markovnikov Z- or E-vinyl thioethers from thiosilane and terminal alkynes under visible-light-induced photoredox/nickel dual catalysis conditions is described. With a judicious choice of a simple nickel catalyst and a ligand, this strategy enables efficient and divergent access to both Z- or E-vinyl thioethers from the same set of simple starting materials. Notably, the approach is free of odorous thiol and has excellent compatibility with functional groups and substrate scope.

EBV-positive inflammatory follicular dendritic cell sarcoma of the colon with clonal immunoglobulin gene rearrangement: A case report and literature review.

Introduction: Epstein-Barr virus-positive (EBV+) inflammatory follicular dendritic cell (FDC) sarcoma is a rare neoplasm characterized by spindle-shaped follicular dendritic cells, marked lymphoplasmacytic infiltration, and a consistent link to EBV. While it typically affects the liver and spleen, it is exceptionally rare in the digestive tract. We present a special case of EBV + inflammatory FDC sarcoma arising in the colon with clonal immunoglobulin (IG) gene rearrangement. Case presentation: A 70-year-old man presented with a one-month history of abdominal distension. Colonoscopy revealed a pedunculated polyp in the ascending colon, which was subsequently removed via endoscopic polypectomy. Histological examination of the colonic polyp demonstrated a pronounced lymphoplasmacytic infiltrate with scattered EBV + neoplastic cells, as evidenced by EBV-encoded small RNA in situ hybridization (EBER ISH). The neoplastic cells were positive for FDC-specific markers, including CD21, CD35, and CD23. Additionally, the tumor exhibited clonal rearrangement of the immunoglobulin heavy chain (IGH) gene. The diagnosis was confirmed as EBV + inflammatory follicular dendritic cell sarcoma. Conclusions: We described an exceptional case of EBV + inflammatory FDC sarcoma presenting as a colonic polyp, featuring a clonal IGH gene rearrangement not previously documented in this colonic tumor type. Heightened awareness of this rare neoplasm within the gastrointestinal tract is essential for both accurate diagnosis and effective patient management.

Artemisia argyi essential oil alleviates asthma by regulating 5-LOX-CysLTs and IDO-1-KYN pathways: Insights from metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi essential oil (AAEO) is a traditional herbal remedy for asthma. However, the potential effect of AAEO on asthma has not been elucidated. AIM OF THE STUDY: To investigate the protective properties of AAEO upon asthma and elucidate its mechanism. MATERIALS AND METHODS: The effects of AAEO in asthma were assessed by histology and biochemical analysis. Then, we integrated real-time reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry and metabolomics analysis to reveal its mechanism. RESULTS: In vivo, AAEO reduced the counts of white blood cells (WBCs) and cytokines in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues, and inhibited secretion of OVA-sIgE and muc5ac. Metabolomics results showed that AAEO can exert therapeutic effects on asthmatic mice by regulating disordered arachidonic acid metabolism and tryptophan metabolism. Further studies shown that AAEO inhibited the expression of 5-LOX and reduced the accumulation of CysLTs in mice. Meanwhile, AAEO promoted the activity of IDO-1, facilitated the conversion of tryptophan to kynurenine, and regulated the imbalance of Treg/Th17 immunity. Immunohistochemical results showed that AAEO promoted the expression of IDO-1. RT-qPCR results showed that AAEO promoted the expression of IL-10 and Foxp3 mRNA, and inhibited the expression of IL-17A and RORγt mRNA, thus regulated the imbalance of Treg/Th17 immunity and exerted its therapeutic effects. CONCLUSION: AAEO treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating lung tissue metabolism. The anti-asthmatic activity of AAEO may be achieved by reprogramming 5-LOX-CysLTs and IDO-1-KYN pathways.

METTL3-mediated N6-methyladenosine modification of STAT5A promotes gastric cancer progression by regulating KLF4.

N6-methyladenosine (m6A) is the predominant post-transcriptional RNA modification in eukaryotes and plays a pivotal regulatory role in various aspects of RNA fate determination, such as mRNA stability, alternative splicing, and translation. Dysregulation of the critical m6A methyltransferase METTL3 is implicated in tumorigenesis and development. Here, this work showed that METTL3 is upregulated in gastric cancer tissues and is associated with poor prognosis. METTL3 methylates the A2318 site within the coding sequence (CDS) region of STAT5A. IGF2BP2 recognizes and binds METTL3-mediated m6A modification of STAT5A through its GXXG motif in the KH3 and KH4 domains, leading to increased stability of STAT5A mRNA. In addition, both METTL3 and IGF2BP2 are positively correlated with STAT5A in human gastric cancer tissue samples. Helicobacter pylori infection increased the expression level of METTL3 in gastric cancer cells, thereby leading to the upregulation of STAT5A. Functional studies indicated that STAT5A overexpression markedly enhances the proliferation and migration of GC cells, whereas STAT5A knockdown has inhibitory effects. Further nude mouse experiments showed that STAT5A knockdown effectively inhibits the growth and metastasis of gastric cancer in vivo. Moreover, as a transcription factor, STAT5A represses KLF4 transcription by binding to its promoter region. The overexpression of KLF4 can counteract the oncogenic impact of STAT5A. Overall, this study highlights the crucial role of m6A in gastric cancer and provides potential therapeutic targets for gastric cancer.

Characteristics of mast cell infiltration in lung adenocarcinoma and its impact on prognosis.

BACKGROUND: The role of mast cells in malignancies remains unclear, and there is no clear correlation between mast cells and tumor microvessels, tumor growth, or lung adenocarcinoma (LUAD) prognosis. This study aims to explore the association between mast cell density (MCD) and intratumoral microvessel density (MVD), clinicopathological parameters, and prognosis in LUAD, by evaluating mast cell infiltration characteristics and their prognostic significance. METHODS: This retrospective investigation involved 238 patients with LUAD undergoing complete resection. Tumor and normal lung tissue sections outside the tumor were immunohistochemically stained for MCD in the intratumoral and outside regions, respectively. CD34 polyclonal antibody was used to measure intratumoral MVD. RESULTS: Intratumoral regions of LUAD had a higher MCD (P < 0.001) than normal lung tissue. In the intratumoral region, MCD and CD34-MVD were positively correlated (r = 0.411, P < 0.001). Intratumoral MCD correlated with sex, smoking history, tumor differentiation, pathological subtype, and tumor size. Female sex (P = 0.012), no smoking history (P = 0.002), acinar predominant type (P = 0.012), and tumor size ≤ 3 cm (P = 0.009) were associated with a higher MCD, whereas poorly differentiated (P = 0.039) and solid/micropapillary predominant types (P = 0.001) were associated with a lower MCD. Higher intratumoral MCD exhibited a marginally improved overall survival, and individuals with higher MCD infiltration ratios (intratumoral MCD/outside the MCD) had higher disease-free and overall survival rates (log-rank P < 0.001). A high MCD infiltration ratio was associated with decreased risk of tumor progression and death following complete resection. CONCLUSION: The tumor microenvironment controls mast cell infiltration in LUAD, and patients with increased intratumoral mast cell infiltration have better prognosis.

Associations of tubal ligation and hysterectomy with serum androgen and estrogen metabolites among postmenopausal women in the Women's Health Initiative Observational Study.

PURPOSE: Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS). METHODS: Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection. RESULTS: Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GMyes 0.46 [95% CI:0.37-0.57] vs. GMno 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GMyes 11.1 [95% CI:8.95-13.9] pmol/L vs. GMno 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GMyes 6.50 [95% CI:5.05-8.37] vs. GMno 4.92 [95% CI:4.00-6.05]). CONCLUSION: While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks.

Impact of anesthesia-related genes on prognosis and tumor microenvironment in hepatocellular carcinoma: A comprehensive analysis.

Hepatocellular carcinoma (HCC), renowned for its bleak prognosis and high recurrence rates, necessitates innovative strategies for prognosis assessment and therapeutic intervention. In this pursuit, we systematically investigated the influence of anesthesia-related genes (ANARGs) on HCC outcomes. Leveraging data from The Cancer Genome Atlas (TCGA), our study scrutinized RNA sequencing data and clinical profiles from 374 HCC patients alongside 50 non-tumor liver samples to unravel ANARG expression patterns and their clinical relevance. Employing consensus clustering, we segregated HCC samples into two distinct subtypes based on ANARG profiles, unveiling significant survival disparities between them. Further differential expression analysis pinpointed pivotal genes and pathways distinguishing these subtypes, notably implicating lipid metabolism and the MTOR signaling pathway in HCC pathogenesis. A prognostic model, comprising five key ANARGs (DAGLA, CYP26B, HAVCR, G6PD and AKR1B), exhibited robust predictive capability for patient outcomes, validated across independent patient cohorts. Furthermore, immune infiltration analysis uncovered a nuanced interplay between ANARG expression and the tumor immune microenvironment, spotlighting variations in immune cell infiltration and function across the identified HCC subtypes. This comprehensive analysis underscores not only the prognostic significance of ANARGs in HCC but also their potential to modulate the tumor microenvironment, providing novel insights for tailoring anesthetic management and therapeutic strategies in HCC care. Our findings advocate for a more integrative approach to HCC management, amalgamating molecular profiling with traditional clinical parameters to refine patient stratification and personalize treatment strategies.

Risk factors of immune checkpoint inhibitor-related pneumonitis after neoadjuvant immunochemotherapy for resectable NSCLC.

BACKGROUND: The incidence of checkpoint inhibitor-associated pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) has been substantiated through large-scale clinical trials or real-world studies. However, reports on CIP incidence within the context of neoadjuvant immunotherapy for resectable NSCLC remain scarce. This study endeavors to investigate the incidence, risk factors, and outcomes of CIP in patients with resectable NSCLC receiving neoadjuvant immunochemotherapy. METHODS: A retrospective, case-control study was conducted on patients diagnosed with NSCLC stages IIA-IIIB who received neoadjuvant immunochemotherapy between January 2018 and September 2022. Patients were stratified into two groups based on the presence or absence of CIP, facilitating a comparative analysis of clinical characteristics, treatment modalities, physiological indicators, and prognostic outcomes . RESULTS: The study cohort comprised 245 patients, with 11.4% (28/245) experiencing CIP. The median period of CIP onset was 70 (range, 40-221) days. The incidence of severe CIP (grade 3-4) was 3.7% (9/245). Patients with CIP showed a higher all-cause mortality rate of 21.4% (6/28) compared to that of patients without CIP. Those who developed CIP exhibited elevated body mass index (BMI) values (p = 0.028) and increased fibrinogen (FIB) levels (p < 0.001), alongside a significant decrease in both diffusing capacity for carbon monoxide (DLCO)% pred (p = 0.001) and DLCO/VA% pred (p = 0.021) after neoadjuvant therapy compared to pre-indicators. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve of three assessed variables (FIB levels, BMI, DLCO) reached 0.806 in predicting CIP occurrence at an early stage. CONCLUSIONS: This cohort demonstrated that elevated BMI, increased FIB levels, and decreased pulmonary diffusion function after neoadjuvant therapy are risk factors of CIP occurrence. Early assessment and continuous monitoring of these indicators are imperative for the predictive identification of CIP, enhancing patient management and outcomes.

A Mechanistic Study of the Osteogenic Effect of Arecoline in an Osteoporosis Model: Inhibition of Iron Overload-Induced Osteogenesis by Promoting Heme Oxygenase-1 Expression.

Iron overload-associated osteoporosis presents a significant challenge to bone health. This study examines the effects of arecoline (ACL), an alkaloid found in areca nut, on bone metabolism under iron overload conditions induced by ferric ammonium citrate (FAC) treatment. The results indicate that ACL mitigates the FAC-induced inhibition of osteogenesis in zebrafish larvae, as demonstrated by increased skeletal mineralization and upregulation of osteogenic genes. ACL attenuates FAC-mediated suppression of osteoblast differentiation and mineralization in MC3T3-E1 cells. RNA sequencing analysis suggests that the protective effects of ACL are related to the regulation of ferroptosis. We demonstrate that ACL inhibits ferroptosis, including oxidative stress, lipid peroxidation, mitochondrial damage, and cell death under FAC exposure. In this study, we have identified heme oxygenase-1 (HO-1) as a critical mediator of ACL inhibiting ferroptosis and promoting osteogenesis, which was validated by HO-1 knockdown and knockout experiments. The study links ACL to HO-1 activation and ferroptosis regulation in the context of bone metabolism. These findings provide new insights into the mechanisms underlying the modulation of osteogenesis by ACL. Targeting the HO-1/ferroptosis axis is a promising therapeutic approach for treating iron overload-induced bone diseases.