Oncoplastic breast-conserving surgery improves cosmetic outcomes without increasing recurrence risk compared to modified radical mastectomy in early breast cancer patients: development and validation of a recurrence risk prediction model.

In the quest for effective treatment of early-stage breast cancer, this study aimed to compare the clinical efficacy of modified radical mastectomy (MRM) and oncoplastic breast-conserving surgery (OBCS). Breast cancer remains a major health concern globally, where early detection and effective treatment strategies are crucial for improving the outcomes of patients. MRM and OBCS are two primary treatment modalities for breast cancer, each with its distinct benefits and challenges. Through a retrospective analysis, we found that although the patients in the OBCS group experienced a longer operation time, they had significantly less intraoperative bleeding, postoperative drainage, and hospitalization time compared to the MRM group. Furthermore, patients in the OBCS group demonstrated higher subjective satisfaction and quality of life scores, along with better objective outcomes. In terms of postoperative complications and recurrence rates, no significant difference was identified between the two groups. However, our multivariate Cox regression analysis identified lymph node metastasis and molecular type as independent prognostic factors for disease-free survival (DFS). Subsequently, we constructed a risk model based on these variables, which was proven to be effective in predicting recurrence, with an area under the risk score curve for recurrence prediction being 0.852. The group with a lower risk score demonstrated a significantly higher DFS rate. Our study suggests that compared with MRM, OBCS can significantly reduce surgical incision, improve patient satisfaction, and does not increase the risk of complications or recurrence. Our risk model, developed using Cox regression, also demonstrated high clinical value in predicting breast cancer recurrence, thereby aiding in personalized patient management and treatment planning.

Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A.

Bone marrow mesenchymal stem cell (BSMC)-derived extracellular vehicles (EVs) have a pivotal therapeutic potential in hepatic fibrosis (HF). Activation of hepatic stellate cells (HSCs) is the key mechanism in HF progression. Downregulation of miR-192-5p was previously observed in activated HSCs. Nonetheless, the functions of BSMC-derived exosomal miR-192-5p in activated HSCs remain unclear. In this study, transforming growth factor (TGF)-ß1 was used to activate HSC-T6 cells to mimic HF in vitro. Characterization of BMSCs and BMSC-derived EVs was performed. Cell-counting kit-8 assay, flow cytometry, and western blotting revealed that TGF-ß1 increased cell viability, promoted cell cycle progression, and induced upregulation of fibrosis markers in HSC-T6 cells. Overexpression of miR-192-5p or BMSC-derived exosomal miR-192-5p suppressed TGF-ß1-triggered HSC-T6 cell activation. RT-qPCR revealed that protein phosphatase 2 regulatory subunit B'' alpha (PPP2R3A) was downregulated in miR-192-5p-overexpressed HSC-T6 cells. Luciferase reporter assay was used for verifying the relation between miR-192-5p and PPP2R3A, which showed that miR-192-5p targeted PPP2R3A in activated HSC-T6 cells. Collectively, BMSC-derived exosomal miR-192-5p targets PPP2R3A and inhibits activation of HSC-T6 cells.

Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.

Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.

Evaluation of indocyanine green combined with methylene blue staining in sentinel lymph node biopsy of breast cancer.

Background: Methylene blue as tracer used in sentinel lymph node biopsy (SLNB) have low detection rate and high false negative rate. Indocyanine green (ICG) can detect the flow of subcutaneous lymphatic vessels and the position of lymph nodes dynamically. This study sought to evaluate the efficacy of ICG combined with methylene blue staining in SLNB of breast cancer. Methods: One hundred and fifty-six early breast cancer patients treated at our hospital from July 2020 to May 2022 were enrolled in this study. SLNB was performed by ICG combined with methylene blue staining under the guidance of the fluorescent tracer navigation system FLI-10B. Standard axillary lymph node dissection (ALND) was performed in patients with sentinel lymph node (SLN) metastasis confirmed by intraoperative frozen pathology, while low ALND was performed in patients with negative SLNs. According to the staining condition, the SLNs were divided into: (I) the combined group (SLNs with methylene blue staining and/or ICG luminescence); (II) the methylene blue group (SLNs with methylene blue staining alone); and (III) the ICG group (SLNs with ICG luminescence alone). The detection rate, accuracy, sensitivity, and false negative rate of SLNB were compared among the 3 groups. Results: A total of 592 SLNs were detected in the combined group (average 3.8 SLNs), yielding a detection rate of 97.4%; the accuracy, sensitivity, and false negative rates were 97.4%, 92.7%, and 7.3%. In the methylene blue group, 390 SLNs were detected (average 2.5 SLNs), yielding a detection rate of 84.6%; the accuracy, sensitivity, and false negative rates were 83.3%, 89.1%, and 10.9%. A total of 483 SLNs were detected in the ICG group (average 3.1 SLNs), the detection rate was 92.9%; the accuracy, sensitivity and false negative rates were 91.7%, 90.9%, and 9.1%. The average number of detected SLNs, detection rate and accuracy rate in the combined group were higher than those in the methylene blue group (P<0.05), and the accuracy rate of the combined group was higher than that of the ICG group (P<0.05). Conclusions: ICG combined with methylene blue staining is a promising and effective tracing strategy in the SLNB of breast cancer with high detection and accuracy rates.

Unveiling the Noncanonical Autophagy-Independent Role of ATG7 and ATG9B in Head and Neck Squamous Cell Carcinoma (HNSCC).

The role of autophagy in cancer remains elusive, and nontargeted autophagy inhibitors have limited therapeutic effects in HNSCC. Here, we systematically analyzed the correlation of autophagy-related genes in HNSCC through TCGA and single-cell sequencing data (GSE103322). ATG9B and ATG7 were found to have noncanonical autophagy-independent functions in HNSCC. Specifically, ATG9B was a protective factor in HNSCC patients through downregulating cancer cell EMT, and ATG7 was correlated with the immunosuppressive environment in HNSCC. Mechanistically, single-cell analysis revealed that ATG9B increased the epithelial phenotype of cancer cells but did not influence EMT signaling pathways. ATG7 was strongly correlated with elevated immunosuppressive checkpoints like PD-1, PD-L1, and CTLA4 in HNSCC. Further single-cell analysis and multiple immunofluorescence colocalization analyses indicated that ATG7 contributed to the high expression of PD-L1 in myeloid cells but not cancer cells. Collectively, our results revealed noncanonical autophagy-independent functions of autophagy-related genes. These results increase understanding of the intricacies of autophagy and may contribute to precision treatment using autophagy-targeted therapies.

Risk of progression in patients with chronic atrophic gastritis: A retrospective study.

Background: Chronic atrophic gastritis (CAG) can progress to gastric cancer (GC) thus requiring endoscopic surveillance. Here, we analyze various aspects of CAG progression, time, and mucosal background, to guide reasonable surveillance. Methods: CAG patients with three or more endoscopies from 2010-2021 were included. All cases were analyzed for rate and time of progression, and cases with operative link on gastritis assessment (OLGA) staging, operative link on gastric intestinal metaplasia assessment (OLGIM) staging, and Kimura-Takemoto classification were further analyzed. Additional investigation of guideline-defined low-risk patients by reviewing endoscopy in the short-term (1-2 years) after baseline identified several patients as high-risk. Results: Ninety-seven (10.4%) of the 929 CAG patients progressed to low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), or GC, during the observation period of 36-129 months (median 53, IQR=24), including 75 (8.1%) cases of LGIN, eight (0.9%) of HGIN, and 14 (1.5%) of GC. Among 170 patients with OLGA/OLGIM at baseline, two (2/2, 100%) GC cases occurred in patients with OLGA/OLGIM III and IV. Of the 236 patients with Kimura-Takemoto classification at baseline, 5/7 (71.4%) cases of GC occurred in patients with C3-O3. Ten, 11, and 25 patients classified as low-risk on the European, British, and Chinese Guidelines, underwent additional endoscopy within 1-2 years, resulting in three (30.0%), four (36.4%), and eight (32.0%) patients being classified as high-risk on these guidelines, respectively. Conclusion: A minority of CAG patients can progress to GC. OLGA/OLGIM III and IV staging are closely associated with progression. Disease-associated risk may be underestimated in one-third of patients classified as low-risk by initial endoscopy.

The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma.

OBJECTIVE: Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. MATERIALS AND METHODS: The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. RESULTS: OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P < 0.0001, n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P < 0.0001), and were correlated with LNM (P < 0.0001) and PNI (P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor. CONCLUSIONS: The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.

Preoperative histogram parameters of dynamic contrast-enhanced MRI as a potential imaging biomarker for assessing the expression of Ki-67 in prostate cancer.

PURPOSE: To investigate whether preoperative histogram parameters of dynamic contrast-enhanced MRI (DCE-MRI) can assess the expression of Ki-67 in prostate cancer (PCa). MATERIALS AND METHODS: A consecutive series of 76 patients with pathology-proven PCa who underwent routine DCE-MRI scans were retrospectively recruited. Quantitative parameters including the volume transfer constant (Ktrans ), rate contrast (Kep ), extracellular-extravascular volume fraction (Ve ), and plasma volume (Vp ) by outlining the three-dimensional volume of interest (VOI) of all lesions were processed. Then, the histogram analyses of these quantitative parameters were performed. The Spearman rank correlation analysis was used to evaluate the correlation of these parameters and Ki-67 expression of PCa. Receiver operating characteristic (ROC) curve analysis was adopted to evaluate the efficacy of these quantitative histogram parameters in identifying high Ki-67 expression from low Ki-67 expression of PCa. RESULTS: Eighty-eight PCa lesions were enrolled in this study, including 31 lesions with high Ki-67 expression and 57 lesions with low Ki-67 expression. The median, mean, 75th percentile, and 90th percentile derived from Ktrans and Kep had a moderately positive correlation with Ki-67 expression (r = 0.361-0.450, p < 0.05), in which both the median and mean of Ktrans had the highest positive correlation (r = 0.450, p < 0.05). The diagnostic efficacy of the Ktrans median, mean, 75th percentile, and 90th percentile, along with the Kep -based median and mean was assessed by the ROC curve. The area under the curve (AUC) of the mean for Ktrans was the highest (0.826). When the cut-off of the mean for Ktrans was ≥0.47/min, its Youden index, sensitivity, and specificity were 0.625, 0.871, and 0.754, respectively. The AUC of the median of Kep was the lowest (0.772). CONCLUSION: The histogram of DCE-MRI quantitative parameters is correlated with Ki-67 expression, which has the potential to noninvasively assess the expression of Ki-67 with patients of PCa.

Poly(sophorolipid) structural variation: effects on biomaterial physical and biological properties.

Diacetylated lactonic sophorolipids (polyLSL[6'Ac,6″Ac]), a biosurfactant, can be efficiently polymerized by ring-opening metathesis polymerization (ROMP). In this paper, enzyme-mediated chemical transformations are developed to regioselectively modify LSL[6'Ac,6″Ac] at sophorose primary hydroxyl positions (6' and 6″). The resulting modified LSLs were polymerized to expand polyLSL structural diversity, that is, polyLSL[6'OH,6″Ac], polyLSL[6'OH,6″OH], polyLSL[6'Bu,6″Ac], polyLSL[6'N3,6″Ac], and polyLSL[6'MA,6″Ac]. Controlled placement of azide and methacrylate at sophorolipid moieties enables the use of "click" reactions to introduce bioactive groups. Thermal analyses of polyLSLs showed that the acylation pattern at sugar moieties has a remarkable effect on chain stiffness and crystallinity. Films of polyLSL[6'Ac,6″Ac], polyLSL[6'OH,6″Ac], and polyLSL[6'Bu,6″Ac] exhibited nonbrittle behaviors with compressive elastic moduli ranging from ∼1.5 to ∼4.9 MPa. PolyLSLs were cytocompatible with human mesenchymal stem cells (h-MSCs), and examination of material-induced osteogenic cell lineage progression uncovered a dependence on polyLSL substitution at sophorose 6'-sites. This research reveals opportunities to regulate polyLSL physical properties and cell response behaviors by variation in substituents at polyLSL sophorolipid moieties.

Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: correlation with the clinico-pathological features of aplastic anemia.

OBJECTIVE: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. METHODS: Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. RESULTS: Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively). CONCLUSION: AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.

Identification of predictive biomarkers for early diagnosis of larynx carcinoma based on microRNA expression data.

The abnormal expression of microRNAs (miRNAs) plays a key role in tumorigenesis. In order to identify potential miRNA biomarkers for early diagnosis of larynx carcinoma, we employed a miRNA microarray technique and applied bioinformatic algorithms to characterize miRNA classifiers in early larynx carcinoma and normal esophageal mucosa tissue samples from 69 patients who were selected retrospectively for this study. We identified 47 miRNAs that were significantly differentially expressed in primary larynx tumor tissues compared to normal tissues using a SAM algorithm. Of these, 30 were up-regulated and 17 down-regulated in early larynx cancer, including hsa-miR-657, which was overexpressed, and hsa-miR-1287, which was underexpressed. These two candidate miRNA biomarkers were combined as a single classifier to recognize the biological characteristics in early larynx carcinoma. Real-time quantitative reverse-transcription PCR validated the microarray results in both trial and test samples. The hsa-miR-657-hsa-miR-1287 classifier displayed high sensitivity and specificity for discriminating between early larynx carcinoma and normal mucosa tissues, suggesting they may be suitable as potential predictive biomarkers for the early diagnosis of larynx carcinoma.

Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: a 3-year follow-up study.

AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM). METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system. RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pylori-infected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P<0.01). However, the grade of IM increased in H pylori -infected group (P<0.05). CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.