[Resveratrol enhances the local antioxidant ability of the ovary in rats with polycystic ovary syndrome].

OBJECTIVE: To investigate the effects of resveratrol (RSV) on ovarian morphology, plasma anti-Müllerian hormone (AMH) and insulin-like growth factor 1 levels (IGF-1), and oxidative stress parameters in rats with polycystic ovary syndrome (PCOS). METHODS: Forty-six rats were randomly divided into a normal control (n = 12), a PCOS model control (n = 12), a rosiglitazone (RSG, n = 11), and an RSV group (n = 11). The PCOS model was established in the latter three groups by rejection of epidehydroandrosterone. The rats in the normal control and PCOS model control groups were treated by gavage of normal saline and those in the RSG and RSV groups by intragastric administration of RSG at 10 mg/(kg·d) and RSV at 3.0 mg/(kg·d), respectively. After 4 weeks of treatment, the ovarian histology was observed under the light microscope, the levels of plasma AMH and IGF-1 measured by ELISA, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the ovarian tissue detected using the Ellman, Sun and AEBI methods, respectively. RESULTS: After a 4-week treatment, statistically significant differences were observed in the above indicators between the normal control and PCOS model control groups (P<0.05). The rats treated with RSG and RSV also showed significant differences in these parameters from the model controls (P<0.05). CONCLUSION: RSV can enhance the local antioxidant capacity of the ovary, reduce the levels of AMH and IGF-1, and improve the morphology of the ovarian tissue in rats with PCOS, indicating its potential value in the treatment of PCOS.

Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS.

BACKGROUND: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS: In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION: Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.

Case series of ovarian neuroendocrine carcinoma: overview of clinicopathological features.

BACKGROUND: Ovarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC. CASE PRESENTATION: We included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date. CONCLUSION: Primary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.

The delaying effect of Qingxin Zishen decoction on ovarian aging: Examining regulation of ovarian mitochondria apoptosis in aged rats.

Ovarian aging is a significant challenge in gynecology, and there is currently no effective treatment for it. However, the medicinal agent Qingxin Zishen decoction (QZD) has shown potential in the treatment of ovarian dysfunction. The present study aimed to evaluate the mitochondrial apoptotic mechanism of delayed ovarian aging in QZD in aging rats. The healthy female Sprague-Dawley (SD) rats (n = 40, 350 ± 20 g) were randomly assigned to different dosage groups and 4-month-old SD rats (n = 10) were assigned to the control group. QZD groups were treated with QZD for four weeks, and ovarian tissues were extracted for mRNA and protein assays to examine the role of the apoptotic pathway in QZD. The results showed that QZD treatment for four weeks significantly increased the mRNA and protein expressions of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2) and Bcl-2/Bax ratio, as well as downregulated the pro-apoptotic genes Bax, caspase-3, and caspase-9. Moreover, QZD treatment effectively reduced the expression of cytochrome C (cyto-C) and apoptotic protease-activating factor 1 (Apaf-1), both of which are components of the intrinsic apoptotic pathway. These changes exhibited a dose-response manner. The findings suggest that QZD might have therapeutic potential in delaying ovarian mitochondrial function decline and in preventing and treating ovarian aging-related diseases by downregulating and upregulating the pro-apoptotic (Bax, caspase-3, caspase-9, cyto-C, Apaf-1) and anti-apoptotic (Bcl-2 and Bcl-2/Bax ratio) genes, respectively.

Dual roles of TRIM3 in colorectal cancer by retaining p53 in the cytoplasm to decrease its nuclear expression.

Colorectal cancer is a very heterogeneous disease caused by the interaction of genetic and environmental factors. P53, as a frequent mutation gene, plays a critical role in the adenoma-carcinoma transition during the tumorous pathological process. Our team discovered TRIM3 as a tumor-associated gene in CRC by high-content screening techniques. TRIM3 demonstrated both tumor-suppressive and tumorigenic features in cell experiments dependent on the cell status of wild or mutant p53. TRIM3 could directly interact with the C terminus of p53 (residues 320 to 393), a common segment of wtp53 and mutp53. Moreover, TRIM3 could exert different neoplastic features by retaining p53 in the cytoplasm to decrease its nuclear expression in a wtp53 or mutp53-dependent pathway. Chemotherapy resistance develops in nearly all patients with advanced CRC and seriously limits the therapeutic efficacies of anticancer drugs. TRIM3 could reverse the chemotherapy resistance of oxaliplatin in mutp53 CRC cells by degradation of mutp53 in the nuclei to downregulate the multidrug resistance gene. Therefore, TRIM3 could be a potential therapeutic strategy to improve the survival of CRC patients with mutp53.

CEBPB regulates the migration, invasion and EMT of breast cancer cells by inhibiting THBS2 expression and O-fucosylation.

Breast cancer (bc) is the second most common type of human malignancies with highest morbidity and mortality in the female population. Therefore, it is essential to develop novel and effective therapies for bc treatment. The main aim of the current study is to investigate the functions of CEBPB and THBS2 in bc and the underlying mechanism. Reverse transcription-quantitative real-time polymerase chain reaction and western blot were performed for the measurement of ribonucleic acids and proteins. Function and mechanism assays were, respectively, conducted for the evaluation of bc biological behaviors and exploration of the potential correlation of genes. According to bioinformatics analyses and experimental results, THBS2, up-regulated in bc tissues and cell lines, could facilitate cell migration, invasion and EMT in bc. CEBPB was validated to facilitate miR-29a-3p transcription, thus negatively modulating THBS2 expression. The results of rescue experiments reflected that CEBPB could regulate the malignant behaviors of bc cells via THBS2. Furthermore, CEBPB was ascertained to inhibit the transcription of B3GALTL to affect THBS2 protein O-fucosylation and secretion. The interaction between THBS2 and ITGB1 was confirmed, and THBS2 was found to activate the PI3K/AKT signaling pathway. To conclude, CEBPB could restrain bc cell migration, invasion and EMT via inhibition on THBS2 expression and O-fucosylation.

Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney.

Background: Immune-related long noncoding RNAs (IrlncRNAs) are recognized as important prognostic factors in a variety of cancers, but thus far, their prognostic value in pediatric rhabdoid tumor of the kidney (pRTK) has not been reported. Here, we clarified the associations between IrlncRNAs and overall survival (OS) of pRTK patients and constructed a model to predict their prognosis. Methods: We accessed RNA sequencing data and corresponding clinical data of pRTK from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. An expression profile of immune-related genes (Irgenes) and lncRNAs of pRTK was extracted from the RNA sequencing data. IrlncRNAs were defined by co-expression analysis of lncRNAs and Irgenes. The limma R package was used to identify differential expression IrlncRNAs. Univariate and multivariate Cox regression analyses were conducted to build a prognostic IrlncRNAs model. The performance of this prognostic model was validated by multimethods, like ROC curve analysis. Results: A total of 1097 IrlncRNAs were defined. Univariate Cox regression analysis identified 7 IrlncRNAs (AC004791.2, AP003068.23, RP11-54O7.14, RP11-680F8.1, TBC1D3P1-DHX40P1, TUNAR, and XXbac-BPG308K3.5) and were significantly associated with OS. Multivariate regression analysis constructed the best prognostic model based on the expression of AC004791.2, AP003068.23, RP11-54O7.14, TBC1D3P1-DHX40P1, and TUNAR. According to the prognostic model, a risk score of each patient was calculated, and patients were divided into high-risk and low-risk groups accordingly. The survival time of low-risk patients was significantly better than high-risk patients (p < 0.001). Univariate (hazard ratio 1.098, 95% confidence interval 1.048-1.149, p value <0.001) and multivariate (hazard ratio 1.095, 95% confidence interval 1.043-1.150, p value <0.001) analyses confirmed that the prognostic model was reliable and independent in prediction of OS. Time-dependent ROC analysis showed that 1-year survival AUC of prognostic model, stage, age, and sex was 0.824, 0.673, 0.531, and 0.495, respectively, which suggested that the prognostic model was the best predictor of survival in pRTK patients. Conclusions: The prognostic model based on 5 IrlncRNAs was robust and could better predict the survival of pRTK than other clinical factors. Additionally, the mechanism of regulation and action of prognosis-associated lncRNAs could provide new avenues for basic research to explore the mechanism of tumor initiation and development in order to prevent and treat pRTK.

PGM5P3-AS1 regulates MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer characteristic of high recurrence rate and poor prognosis. According to previous studies and bioinformatics prediction, PGM5P3-AS1 has been found to be significantly down-regulated in TNBC cells. In addition, cell ferroptosis has become a hotspot in breast cancer research and TNBC has been reported to be more sensitive to ferroptosis than receptor positive breast cancer. Hence, we aim at exploring the molecular mechanism of PGM5P3-AS1 in TNBC cells and further explore whether PGM5P3-AS1 can inhibit TNBC progression via promoting cell ferroptosis. METHODS: The expression of genes in TNBC cells was verified by RT-qPCR assay. Functional assays were taken to evaluate the impact PGM5P3-AS1 may exert on TNBC progression. The regulatory pattern of PGM5P3-AS1 on cell ferroptosis in TNBC was validated through mechanism assays. RESULTS: PGM5P3-AS1 was proved to be down-regulated in TNBC cells and suppressed TNBC cell proliferation as well as migration. PGM5P3-AS1 promoted cell ferroptosis in TNBC by recruiting RNA-binding protein (RBP) NOP58 to stabilize MAP1LC3C mRNA, and thus inhibiting TNBC progression. CONCLUSION: PGM5P3-AS1 regulated MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of TNBC.

circRNA RPPH1 Facilitates the Aggravation of Breast Cancer Development by Regulating miR-542-3p/ARHGAP1 Pathway.

Background: Circular RNAs (circRNAs) have important roles in human malignancies, including breast cancer (BC). In this study, we explored the function of circRNA ribonuclease P RNA component H1 (circ_RPPH1) in BC development and clarify the mechanistic pathway. Materials and Methods: Expression of circ_RPPH1, microRNA-542-3p (miR-542-3p), and Rho GTPase-activating protein 1 (ARHGAP1) in BC tissues and cells was determined by quantitative real-time polymerase chain reaction or Western blot assay. The stability of circ_RPPH1 was confirmed by RNase R and actinomycin D treatment. Cell viability and colony formation ability were measured by methyl thiazolyl tetrazolium (MTT) assay and colony formation assay, respectively. Western blot analysis was also used to detect proliferation biomarker (Ki67) and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, and vimentin). Flow cytometry and Transwell assays were performed to monitor cell apoptosis, migration, and invasion. The binding potency between miR-542-3p and circ_RPPH1 or ARHGAP1 was validated by dual-luciferase reporter assay. Functional role of circ_RPPH1 in vivo was investigated by xenograft tumor reporter assay. Results: Upregulation of circ_RPPH1 and ARHGAP1, and downregulation of miR-542-3p were detected in BC tissues and cells. circ_RPPH1 knockdown or miR-542-3p introduction inhibited BC cell proliferation and metastasis, while promoted apoptosis in vitro. circ_RPPH1 sponged miR-542-3p to upregulate ARHGAP1 expression, thereby affecting BC progression. Moreover, depletion of circ_RPPH1 suppressed tumor growth in vivo. Conclusions: circ_RPPH1 contributed to BC tumorigenesis by sponging miR-542-3p and upregulating ARHGAP1, affording a novel mechanistic pathway in BC development.

Protective effect of antioxidant peptides from grass carp scale gelatin on the H2O2-mediated oxidative injured HepG2 cells.

The protective effect of antioxidant peptides from grass carp scale gelatin on hydrogen peroxide (H2O2)-mediated oxidative injured HepG2 cells was investigated, and the protective mechanism as well as peptide structure were studied. Pretreated with grass carp scale gelatin hydrolysates (GSGH) for 24 h significantly increased the survival rates and decreased the apoptosis rates of H2O2-mediated oxidative injured HepG2 cells. The increase in SOD, CAT and GPX activities, reduce in ROS level and MDA content, and weaken in damage on cell membrane and DNA could be responsible for the protective effect of GSGH on H2O2-mediated oxidative injured HepG2 cells. Peptide sequences of GSGH were analyzed by LC-ESI-Q-Orbitrap-MS/MS, and results showed that most of them were low molecular weight peptide at 358-986 Da. Synergistic effect existed among antioxidant peptides and contributed to the strong antioxidant activities of GSGH.

Long Noncoding-RNA Component of Mitochondrial RNA Processing Endoribonuclease Promotes Carcinogenesis in Triple-Negative Breast Cancer Cells via the Competing Endogenous RNA Mechanism.

PURPOSE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer. Increasing evidence supports that dysregulation of long noncoding RNAs (lncRNAs) plays a vital role in cancer progression. RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a lncRNA, is characterized as a tumor-propeller in some cancers, but its mechanism in TNBC remains poorly understood. This study aimed to determine whether and how RMRP functions in TNBC. METHODS: Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays and cell apoptosis by flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Cell migration and invasion were determined by transwell assays. RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pulldown assays were implemented to assess the interaction of RMRP with other molecules in TNBC cells. RESULTS: RMRP expression was elevated in TNBC cells. RMRP knockdown repressed cell proliferation, migration, and invasion, but induced apoptosis in TNBC. In addition, RMRP was found to target microRNA-766-5p (miR-766-5p) in TNBC cells. Silencing miR-766-5p enhanced cell viability and decreased apoptosis, whereas miR-766-5p overexpression had opposite effects. Furthermore, miR-766-5p was found to bind to yes-associated protein 1 (YAP1). Moreover, miR-766-5p inhibition reversed the repressive effect of RMRP knockdown on the malignant progression of TNBC. CONCLUSION: The present study manifested that RMRP promotes the growth, migration, and invasion of TNBC cells via the miR-766-5p/YAP1 axis. These findings provide novel perspectives for TNBC treatment.

circHIPK3 (hsa_circ_0000284) Promotes Proliferation, Migration and Invasion of Breast Cancer Cells via miR-326.

PURPOSE: circHIPK3 has carcinogenic or anti-tumor effects on different cancers. However, there is no relevant research showing whether circHIPK3 was involved in breast cancer (BCa). In this research, the aim was to analyze the function and possible molecular mechanism of circHIPK3 in BCa. METHODS: The expression of circHIPK3 in human BCa tissues and cells was detected by real-time quantitative PCR (RT-qPCR). CircInteractome and dual-luciferase assays were performed to detect circRNA-miRNA targeting relationship. Ribonuclease R treatment, RT-qPCR, Western blot and immunohistochemistry were performed to determine the stability, expressions, abundance of target genes. Loss-of-function or gain-of-function experiments were used to analyze the effects of circHIPK3 and miR-326 on BCa in vivo and in vitro. In vitro, MCF7 and BT20 cells were transfected with circHIPK3 or sicircHIPK3 or miR-326 mimic; in vivo, female BALB/c mice were subcutaneously injected with MCF7 cells (transfected with CirchipK3 or miR-326 mimic) to establish xenograft models. RESULTS: The circular structure of circHIPK3 was abundantly expressed in the cytoplasm and was up-regulated in BCa. Silenced circHIPK3 suppressed malignant phenotype of BCa cells. MiR-326 interacted with circHIPK3 and the two were negatively correlated. Overexpressed circHIPK3 promoted cell viability, proliferation, migration and invasion, but inhibited apoptosis. Moreover, overexpressed circHIPK3 promoted the expressions of EMT-related genes and antiapoptotic genes, but inhibited proapoptotic gene expressions. Overexpressed circHIPK3 promoted tumor growth and Ki-67 levels, inhibited apoptosis in vivo. The above mentioned effects of circHIPK3 were reversed by miR-326 in vitro or in vivo. CONCLUSION: circHIPK3 promoted proliferation, migration and invasion of BCa cells through regulating miR-326.

Loco-regional recurrence trend and prognosis in young women with breast cancer according to molecular subtypes: analysis of 1099 cases.

BACKGROUND: The number of young patients diagnosed with breast cancer is on the rise. We studied the rate trend of local recurrence (LR) and regional recurrence (RR) in young breast cancer (YBC) patients and outcomes among these patients based on molecular subtypes. METHODS: A retrospective cohort study was conducted based on data from Tianjin Medical University Cancer Institute and Hospital for patients ≤ 35 years of age with pathologically confirmed primary invasive breast cancer surgically treated between 2006 and 2014. Patients were categorized according to molecular subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year rates for LR, RR, and distant metastases (DM) were estimated by Kaplan-Meir statistics. Nelson-Aalen cumulative-hazard plots were used to describe local recurrence- and distant metastasis-free intervals. RESULTS: We identified 25,284 patients with a median follow-up of 82 months, of whom 1099 (4.3%) were YBC patients ≤ 35 years of age. The overall 5-year LR, RR, and DM rates in YBC patients were 6.7%, 5.1%, and 16.6%, respectively. The LR and RR rates demonstrated a decreasing trend over time (P = 0.028 and P = 0.015, respectively). We found that early-stage breast cancer and less lymph node metastases increased over time (P = 0.004 and P = 0.007, respectively). Patients with HR-/HER2+ status had a significantly higher LR (HR 20.4; 95% CI, 11.8-35.4) and DM (HR 37.2; 95% CI, 24.6-56.3) at 10 years. Breast-conserving surgery (BCS) or mastectomy did not influence rates of LR and RR. In the overall population, the 5-year survival of YBC patients exceeded 90%. CONCLUSIONS: The rates of LR and RR with YBC patients demonstrated a downward trend and the proportion of early-stage breast cancer increased between 2006 and 2014. We report the highest LR rates in this young population were associated with HR-/HER2+ tumors.

LINC00665 Stimulates Breast Cancer Progression via Regulating miR-551b-5p.

INTRODUCTION: Long intergenic non-protein coding RNA 665 (LINC00665) has been revealed to contribute cancer progression in many cancer types including liver and gastric cancer. However, the roles of LINC00665 in breast cancer (BC) remain to be explored. METHODS: We explored LINC00665 expression in BC tissues and normal tissues at GEPIA. Then, its expression in BC cells (HCC-1937, MDA-MB-231, and MCF-7) and normal cells (MCF10A) was analyzed with qRT-PCR. In addition, the mechanisms of LINC00665 in BC were explored using bioinformatic analyses, luciferase activity reporter assay, RNA pull-down assay, and rescue experiments. RESULTS: We showed LINC00665 expression was significantly increased in both BC tissues and cells. The knockdown of LINC00625 significantly inhibits BC cell growth and promotes cell apoptosis in vitro, while the overexpression of LINC00625 has the opposite effects on BC progression. LINC00665 could affect BC progression via regulating miR-551b-5p. DISCUSSION: Taken together, our study showed that the LINC00665/miR-551b-5p axis was involved in the progression of BC.

CircMMP11 regulates proliferation, migration, invasion, and apoptosis of breast cancer cells through miR-625-5p/ZEB2 axis.

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to play significant roles in regulating gene expression in tumorigenesis, including breast cancer (BC). This study was designed to explore the role and underlying molecular mechanisms of circMMP11 in BC. METHODS: The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used for examining expression of circMMP11, microRNA-625-5p (miR-625-5p), and Zinc finger E-box binding homeobox-2 (ZEB2). The protein expression of ZEB2, Vimentin, and E-cadherin was assessed by western blot assay. The proliferation ability of BC cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The transwell assay was used to measure migration and invasion of BC cells. The apoptotic cells were examined by flow cytometry assay. The interaction association among circMMP11, miR-625-5p, and ZEB2 was confirmed by RNA pull-down and dual-luciferase report assays. A xenograft experiment was established to clarify the role of circMMP11 silencing in vivo. RESULTS: We found that circMMP11 and ZEB2 were overexpressed in BC tissues and cells compared with controls. The suppression of circMMP11 or ZEB2 repressed proliferation, migration, and invasion while induced apoptosis of BC cells. Additionally, miR-625-5p, interacted with ZEB2, was a target of circMMP11 in BC cells. CircMMP11 regulated the expression of ZEB2 by targeting miR-625-5p. Knockdown of circMMP11-mediated effects on BC cells could be abolished by overexpression of ZEB2. Consistently, silencing of circMMP11 impeded the tumor growth in vivo. CONCLUSIONS: CircMMP11/miR-625-5p/ZEB2 axis affected proliferation, migration, invasion, and apoptosis of BC cells through the mechanism of competing endogenous RNAs (ceRNA), indicating that circMMP11 was an oncogenic circRNA in BC.

The Effect of Subsequent Pregnancy on Prognosis in Young Breast Cancer Patients (≤35 Years Old) According to Hormone Receptor Status.

PURPOSE: We aimed to examine the effect of pregnancy on prognosis in young breast cancer (YBC) patients with hormone receptor (HR) positive after surgery and the safety of interrupting endocrine therapy (ET). METHODS: A retrospective cohort study was performed in patients who became pregnant after BC surgery under the age of 35 and were matched (1:4) to nonpregnant patients from 2006 to 2014. The primary endpoints were disease-free survival (DFS) and overall survival (OS) in HR-positive BC patients, and the secondary endpoints were DFS and OS in HR-negative BC patients and the whole population. Subgroup analyses included the DFS of patients who became pregnant within 5 years after surgery and DFS according to the ET interval time (≤ 30 months v > 30 months) in the pregnant group. RESULTS: A total of 1323 YBC patients were collected in our study, which included 68 pregnant patients and 264 matched nonpregnant patients. There were no statistically significant differences in DFS and OS among HR-positive patients (P=0.657, P=0.250, respectively) and the whole population (P=0.058, P=0.152, respectively). A BC pregnancy interval ≤ 5 years showed a better DFS (P=0.042), and an ET interval ≤ 30 months had a worse DFS (P = 0.01). CONCLUSION: This study did not observe a worse prognosis in patients with HR-positive disease who became pregnant after BC surgery, and an ET interval less than 30 months in pregnant patients led to a worse outcome. Patients were able to become pregnant within 5 years after surgery.

Liver fibrosis is a major risk factor for liver regeneration: A comparison between healthy and fibrotic liver.

BACKGROUND: Blood flow factors, such as congestion or ischemia after hepatectomy, have a significant impact on liver regeneration, but with the popularization of precise hepatectomy technology, segmental hepatectomy without congestion or ischemia has become the preferred treatment. Our aim is to investigate the factors affecting liver regeneration after hepatectomy without blood flow changes, and to provide clinical evidence for surgeons on the timing of second hepatectomy for cirrhosis patients with hepatocellular carcinoma (HCC). METHODS: This study retrospectively analyzed data from patients who underwent right hepatectomy without middle hepatic vein (MHV) in West China Hospital between January 2016 and January 2018. Eighteen living-donors without MHV as normal group and 45 HCC patients, further classified into 3 subgroups based on the severity of fibrosis using the Scheure system. Demographic data, pre- and postoperative liver function indexes, and remnant liver volume (RLV) were retrospectively compared. We also analyzed the remnant liver regeneration rate (RLRR) post-operatively in each group. The significant indexes in univariate analysis were further analyzed using both receiver operating characteristic (ROC) analysis and multivariate regression analysis. RESULTS: Liver regeneration occurred in both living-donor and HCC groups after hepatectomy; the RLRRs at 1 month were 59.46 ±â€Š10.39% and 57.27 ±â€Š4.77% (P = .509), respectively. Regeneration in the cirrhosis group occurred more slowly and less completely compared with that in other groups. The regeneration rate in the first 6 months showed rapid increase and the RLRR reached above 70% in cirrhosis group. Multivariate and ROC analyses revealed that Alb and the hepatic fibrosis grade in the early postoperative period were significant predictors of remnant liver regeneration. CONCLUSION: The liver regenerated in all HCC patients; however, regeneration was significantly slower and less complete compared with the normal liver, especially in the patients with cirrhosis. Therefore, it can be concluded that the degree of liver fibrosis is a major predictor of liver regeneration. Furthermore, the optimal time for second resection in recurrent HCC patients with cirrhosis was 6 months after the first operation.

Comparison of Long-Term Outcomes and Sequelae Between Children and Adult Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.

PURPOSE: Our purpose was to compare long-term survival outcomes and sequelae between child and adult nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy. METHODS AND MATERIALS: Data on 285 patients with NPC aged ≤18 years at diagnosis and treated with intensity modulated radiation therapy between January 2004 and November 2016 were retrospectively reviewed. A propensity score matching method was adopted to screen matched adult patients with NPC at a ratio of 1:3. Survival outcomes and treatment-related toxicities between child and adult groups were compared. RESULTS: In total, 159 children and 477 adult patients with NPC were included in this study. The 5-year overall survival, distant metastasis-free survival, locoregional relapse-free survival, and disease-free survival between children and adults were 89.2% versus 83.6% (P = .144), 88.7% versus 83.5% (P = .124), 96.4% versus 89.1% (P = .013), and 86.5% versus 77.3% (P = .021), respectively. Subgroup analyses revealed that the young age was an independent prognostic factor of overall survival, distant metastasis-free survival, and locoregional relapse-free survival in the advanced N stage (N2-3) group and disease-free survival in the advanced T stage (T3-4) group and N2-3 and stage III-IVA groups. The most common sequela was ototoxicity (68.9%) in child patients and xerostomia (70.8%) in adult patients. Adult survivors had a significantly higher incidence of grade 3 to 4 late toxicities in xerostomia (17.6% vs 8.9%; P = .004), skin dystrophy (9.3% vs 3.7%; P = .022), neck fibrosis (8.3% vs 4.4%; P < .001), and radiation encephalopathy (0.8% vs 0; P = .006). Child survivors were more likely to develop grade 3 to 4 growth retardation and endocrine insufficiency (3.0% vs 0.3%; P = .014). CONCLUSIONS: Child patients with NPC achieved significantly better survival outcomes but fewer late toxicities than adult patients. However, we should pay great attention to growth problems of child survivors.

Poor preoperative sleep quality is a risk factor for severe postoperative pain after breast cancer surgery: A prospective cohort study.

The aim of this study was to assess the effect of preoperative sleep quality on acute postoperative pain in breast cancer patients.The Pittsburgh Sleep Quality Index questionnaire (PSQI) was used to assess the overall sleep status of women scheduled for unilateral modified radical mastectomy in the past month. Based on the responses, patients were allocated to good sleep group or poor sleep group. Postoperatively, acute pain was assessed using the numerical rating score in the first 24 hours; in addition, the requirement of analgesics and the incidence of postoperative complications were recorded.A total of 108 breast surgery patients were enrolled. Based on the PSQI results, 55 (51%) patients were allocated to poor sleep group and 53 (49%) to good sleep group. Pain scores were similar in the 2 groups at the end of surgery (P = .589); however, poor sleep group reported higher postoperative pain scores than the good sleep group at 2 (P = .002), 6 (P < .001), 12 (P < .001), and 24 (P = .002) hours after surgery. The incidence of severe pain in the poor sleep group was higher than that in the good sleep group (27% vs 8%, P = .018), and the ratio of participants who required rescued analgesics was greater in the poor sleep group (52% vs 22%, P = .002). In addition, patients with poor sleep quality had more postoperative complications and longer hospital stay.In this study, breast cancer patients with poor preoperative sleep quality reported more severe postoperative pain, required more analgesics, experienced more complications, and had longer hospital stay.

Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine-induced killer cells in 294 patients.

OBJECTIVE: To examine the efficacy and safety of a sequential combination of chemotherapy and autologous cytokine-induced killer (CIK) cell treatment in triple-negative breast cancer (TNBC) patients. METHODS: A total of 294 post-surgery TNBC patients participated in the research from January 1, 2009 to January 1, 2015. After adjuvant chemotherapy, autologous CIK cells were introduced in 147 cases (CIK group), while adjuvant chemotherapy alone was used to treat the remaining 147 cases (control group). The major endpoints of the investigation were the disease-free survival (DFS) and overall survival (OS). Additionally, the side effects of the treatment were evaluated. RESULTS: In the CIK group, the DFS and OS intervals of the patients were significantly longer than those of the control group (DFS: P = 0.047; OS: P = 0.007). The multivariate analysis demonstrated that the TNM (tumor-node-metastasis) stage and adjuvant CIK treatment were independent prognostic factors for both DFS [hazard ratio (HR) = 0.520, 95% confidence interval (CI):0.271-0.998, P = 0.049; HR = 1.449, 95% CI:1.118-1.877, P = 0.005, respectively] and OS (HR=0.414, 95% CI:0.190-0.903, P = 0.027; HR = 1.581, 95% CI:1.204-2.077, P = 0.001, respectively) in patients with TNBC. Additionally, longer DFS and OS intervals were associated with increased number of CIK treatment cycles (DFS: P = 0.020; OS: P = 0.040). The majority of the patients who benefitted from CIK cell therapy were relatively early-stage TNBC patients. CONCLUSION: Chemotherapy in combination with adjuvant CIK could be used to lower the relapse and metastasis rate, thus effectively extending the survival time of TNBC patients, especially those at early stages.