The Potential Mechanism of Remission in Type 2 Diabetes Mellitus After Vertical Sleeve Gastrectomy.

In recent years, there has been a gradual increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), with bariatric surgery remaining the most effective treatment strategy for these conditions. Vertical sleeve gastrectomy (VSG) has emerged as the most popular surgical procedure for bariatric/metabolic surgeries, effectively promoting weight loss and improving or curing T2DM. The alterations in the gastrointestinal tract following VSG may improve insulin secretion and resistance by increasing incretin secretion (especially GLP-1), modifying the gut microbiota composition, and through mechanisms dependent on weight loss. This review focuses on the potential mechanisms through which the enhanced action of incretin and metabolic changes in the digestive system after VSG may contribute to the remission of T2DM.

Rapid discovery of natural skin-lightening ingredients based on an integrated screening strategy based on molecular docking and zebrafish model.

BACKGROUND: Natural herbs have been widely considered a reservoir for skin-lightening ingredients, but discovery of the effective ingredients from herbs remains a large challenge. AIM: This research aimed to rapidly identify compounds with skin-lightening activity in Chinese herbs. METHODS: The structure information of herbal compounds was collected and selected from the open-source data. High throughput virtual screening (HTVS) and Extra precision (XP) docking modes were used to screen for compounds that could bind to the mushroom tyrosinase involved in melanin synthesis. Furthermore, molecular dynamics (MD) simulations were introduced to assess the binding stability of those compounds with the key target protein. The candidate compounds found by this kind of multidimensional molecular screening were finally tested for their ability to inhibit pigmentation and potential toxicity using an in vivo zebrafish animal model. RESULTS: A Natural Compounds Database was established with 5616 natural compounds. Fourteen compounds with favorable binding capability were screened by the XP docking mode with mushroom tyrosinase and five compounds among them were found to have superior dynamic binding performance through MD simulations. Then the Zebrafish animal experiments revealed that two components, sennoside B (SB) and sennoside C (SC), could significantly inhibit melanogenesis rather than the other three compounds. Meanwhile, there were no obvious side effects observed in SB and SC about the morphology, heart rate, or body length of zebrafish. CONCLUSION: A strategy for rapid screening of compounds with whitening activity has been established, and two potent skin-lightening compounds, SB and SC, have been identified from a vast library of herbal compounds. This study revealed that SB and SC have potential for topical use in skin lightening for the first time. The findings of this study would provide an important theoretical basis for the application of these two compounds in the cosmetic field in the future.

Synergistic therapeutic effect of ginsenoside Rg3 modified minoxidil transfersomes (MXD-Rg3@TFs) on androgenic alopecia in C57BL/6 mice.

Inflammation in hair follicles will reduce the effectiveness of minoxidil (MXD) in the treatment of androgen alopecia (AGA) caused by elevated androgen levels. To target multiple physiological and pathological processes in AGA, a novel natural bioactive compound modified transfersomes (MXD-Rg3@TFs) was prepared to replace cholesterol that may disrupt hair growth, with ginsenosides Rg3 (Rg3) that have anti-inflammatory effects on AGA. The effects of MXD, Rg3 and their combination on AGA were evaluated using dihydrotestosterone (DHT) induced human dermal papilla cells (DPCs), and the results showed that the combination of MXD and Rg3 can significantly promote the proliferation, reduce the level of intracellular ROS and inflammatory factors, and inhibit the aging of DHT induced DPCs. Compared with cholesterol membrane transfersomes (MXD-Ch@TFs), MXD-Rg3@TFs has similar deformability, smaller particle size and better stability. MXD-Rg3@TFs has also significant advantages in shortening telogen phase and prolonging the growth period of hair follicles in C57BL/6 mice than MXD-Ch@TFs and commercial MXD tincture. The prominent ability of MXD-Rg3@TFs to inhibit the conversion of testosterone to DHT and reduce the level of inflammatory factors suggested that Rg3 and MXD in MXD-Rg3@TFs have synergistic effect on AGA therapy. MXD-Ch@TFs with no irritation to C57BL/6 mice skin is expected to reduce the dose of MXD and shorten the treatment time, which would undoubtedly provide a promising therapeutic option for treatment of AGA.

Clinical risk factors and Risk assessment model for Anastomotic leakage after Rectal cancer resection.

BACKGROUND: Anastomotic leakage (AL) is the most serious complication after rectal cancer surgery. Risk factors associated with AL have been documented in previous studies; however, the consensus is still lacking. In this retrospective study, we aimed to identify risk factors for AL after rectal cancer resection and to create an accurate and effective tool for predicting the risk of this complication. METHODS: The study cohort comprised of 276 patients with rectal cancer who had undergone anterior resection between 2015 and 2020. Twenty-four selected variables were assessed by univariate and multivariate logistic regression analyses to identify independent risk factors of AL. A risk assessment model for predicting the risk of AL was established on the basis of the regression coefficients of each identified independent risk factor. RESULTS: Anastomotic leakage occurred in 20 patients (7.2%, 20/276). Multivariate analysis identified the following variables as independent risk or protective factors of AL: perioperative ileus (P < 0.001, odds ratio [OR] = 14.699), tumor size ≥5 cm (P = 0.025, OR = 3.925), distance between tumor and anal verge <7.5 cm (P = 0.045, OR = 3.512), obesity (P = 0.032, OR = 7.256), and diverting stoma (P = 0.008, OR = 0.143). A risk assessment model was constructed and patients were allocated to high-, medium-, and low-risk groups on the basis of risk model scores of 5-7, 2-4, and 0-1, respectively. The incidences of AL in these three groups were 61.5%, 11.9%, and 2.0%, respectively (P < 0.001). CONCLUSIONS: Our risk assessment model accurately and effectively identified patients at high risk of AL and could be useful in aiding decision-making aimed at minimizing adverse outcomes associated with leakage.

LINC00478-derived novel cytoplasmic lncRNA LacRNA stabilizes PHB2 and suppresses breast cancer metastasis via repressing MYC targets.

BACKGROUND: Metastasis is the predominant cause of mortality in patients with breast cancer. Long noncoding RNAs (lncRNAs) have been shown to drive important phenotypes in tumors, including invasion and metastasis. However, the lncRNAs involved in metastasis and their molecular and cellular mechanisms are still largely unknown. METHODS: The transcriptional and posttranscriptional processing of LINC00478-associated cytoplasmic RNA (LacRNA) was determined by RT-qPCR, semiquantitative PCR and 5'/3' RACE. Paired-guide CRISPR/cas9 and CRISPR/dead-Cas9 systems was used to knock out or activate the expression of LacRNA. Cell migration and invasion assay was performed to confirm the phenotype of LacRNA. Tail vein model and mammary fat pad model were used for in vivo study. The LacRNA-PHB2-cMyc axis were screened and validated by RNA pulldown, mass spectrometry, RNA immunoprecipitation and RNA-seq assays. RESULTS: Here, we identified a novel cytoplasmic lncRNA, LacRNA (LINC00478-associated cytoplasmic RNA), derived from nucleus-located lncRNA LINC00478. The nascent transcript of LINC00478 full-length (LINC00478_FL) was cleaved and polyadenylated, simultaneously yielding 5' ends stable expressing LacRNA, which is released into the cytoplasm, and long 3' ends of nuclear-retained lncRNA. LINC00478_3'RNA was rapidly degraded. LacRNA significantly inhibited breast cancer invasion and metastasis in vitro and in vivo. Mechanistically, LacRNA physically interacted with the PHB domain of PHB2 through its 61-140-nt region. This specific binding affected the formation of the autophagy degradation complex of PHB2 and LC3, delaying the degradation of the PHB2 protein. Unexpectedly, LacRNA specifically interacted with PHB2, recruited c-Myc and promoted c-Myc ubiquitination and degradation. The negatively regulation of Myc signaling ultimately inhibited breast cancer metastasis. Furthermore, LacRNA and LacRNA-mediated c-Myc signaling downregulation are significantly associated with good clinical outcomes, take advantage of these factors we constructed a prognostic predict model. CONCLUSION: Therefore, our findings propose LacRNA as a potential prognostic biomarker and a new therapeutic strategy.

pH-sensitive molybdenum (Mo)-based polyoxometalate nanoclusters have therapeutic efficacy in inflammatory bowel disease by counteracting ferroptosis.

Current therapeutic drugs for ulcerative colitis (UC) remained inadequate due to drug dependence and unacceptable adverse events. Reactive oxygen species (ROS) played a critical role in the occurrence and development of UC, which most likely benefited from treatment in scavenging ROS. In this study, we developed a pH-sensitive molybdenum-based polyoxometalate (POM) nanocluster, which might contribute to site specific colonic delivery and enhance systemic efficacy of UC treatment. Our results demonstrated that POM displayed robust ROS scavenging ability in vitro. POM could significantly alleviate the enteric symptoms and inflammatory indicators in DSS-induced UC mouse models. Flow cytometry showed an effective diminishment of macrophages, neutrophils and T cells infiltration after POM administration in UC models. Also, for the first time, we demonstrated that POM interfered with metabolic pathway associated to oxidative stress and partially improved the abnormal production of intestinal metabolites in UC to some extent. Benefiting from the ROS scavenging ability, POM attenuated ferroptosis in DSS induced UC, as evidenced by increase of GSH, down-expression of GPX4 and improvement in mitochondrial morphological changes. Meanwhile, there were no side effects on normal tissues. Thus, our powerful therapeutic effects pioneered the application of POM for safer and more effective POM-based UC therapy.

Ampelopsin induces MDA-MB-231 cell cycle arrest through cyclin B1-mediated PI3K/AKT/mTOR pathway in vitro and in vivo.

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.

Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway.

Background: Breast cancer is one of the leading causes of cancer-related death among women, and the pathological status of axillary lymph nodes is an important predictor of prognosis. However, the mechanism involved in this early stage of metastasis remains largely unknown. Methods: Microarray analysis was used to carry out differential genomics analyses between matched pairs of metastatic sentinel lymph node tissues and breast primary tumors. The CRISPR/Cas9 gene editing system was used for in vivo screening by transplanting a loss-of-function cell pool into immunocompromised mice. MAGeCK was used to analyze the screening results. Survival analysis was performed via the Kaplan-Meier method. Cell proliferation, wound healing, migration and invasion assays were performed to confirm the phenotype. A tail vein model and subcutaneous xenotransplanted tumor model were used for the in vivo study. The relationship between coiled-coil domain containing 102B (CCDC102B) and receptor for activated C kinase 1 (RACK1) was examined using coimmunoprecipitation, mass spectrometry, nuclear protein extraction and immunofluorescence assays. The primary biological functions and pathways related to CCDC102B were enriched by RNA sequencing. Results: We identified CCDC102B through screening and found that it was significantly upregulated in metastatic lesions in lymph nodes compared to matched primary tumors. Increased expression of CCDC102B promoted breast cancer metastasis in vitro and in vivo. Additionally, high expression of CCDC102B was correlated with poor clinical outcomes in breast cancer patients. We further identified that CCDC102B was stabilized by the loss of RACK1, a protein negatively correlated with breast cancer metastasis. Mechanistically, we found that RACK1 promoted CCDC102B lysosomal degradation by mediating chaperone-mediated autophagy (CMA). The aggressive behavior of CCDC102B in breast cancer cells could be reversed by the expression of RACK1. Moreover, CCDC102B was correlated with the significant enrichment of NF-κB pathway components. Overexpressing CCDC102B led to less interaction between RACK1 and IKKa. Thus, CCDC102B positively regulates the NF-κB pathway by interacting with RACK1. Conclusion: Taken together, our findings uncover a novel role of CCDC102B in breast cancer metastasis. CCDC102B serves as a potential metastasis promoter by regulating the activation of the NF-κB pathway and can be degraded by RACK1 via CMA.

Application Value of Combined Detection of NLR, PNI, D-Dimer, CD3+ T Lymphocytes, and CEA in Colorectal Cancer Screening.

Objective: To investigate the application value of combined detection of neutrophil-lymphocyte ratio (NLR), prognostic nutrition index (PNI), D-dimer (D-D), CD3+ T lymphocytes (CD3+ T), and carcinoembryonic antigen (CEA) in colorectal cancer screening. Methods: The study cohort comprised 187 colorectal cancer patients and 100 mixed hemorrhoids patients as controls from January 2019 to August 2021 at the Fifth Affiliated Hospital of Sun Yat-sen University. Comparing the levels of NLR, PNI, D-D, CD3+ T, and CEA between the two groups of subjects, drawing receiver operating characteristic (ROC) curve evaluates the efficacy of single and combined detection for colorectal cancer screening. Results: Compared with the control group, the levels of NLR, D-D, and CEA in the colorectal cancer group were significantly increased, while the levels of PNI and CD3+ T were significantly decreased (P < 0.05). ROC curve analysis showed that the combined detection of NLR, PNI, D-D, CD3+ T, and CEA for colorectal cancer screening had an AUCROC of 0.943, a sensitivity of 84.49%, a specificity of 91.00%, and a Youden index of 0.75, and its screening efficacy was significantly superior to that of a single detection (P < 0.001). Conclusion: The combined detection of NLR, PNI, D-D, CD3+ T, and CEA has a high clinical application value for colorectal cancer and can provide a reference for early screening and auxiliary diagnosis of colorectal cancer.

An 85-amino-acid polypeptide from Myrmeleon bore larvae (antlions) homologous to heat shock factor binding protein 1 with antiproliferative activity against MG-63 osteosarcoma cells in vitro.

Background: Venomous arthropods have substances in their venom with antiproliferative potential for neoplastic cells. Objectives: To identify a polypeptide from Myrmeleon bore (antlion) with antiproliferative activity against neoplastic cells, and to elucidate the molecular mechanism of the activity. Methods: We used gel filtration and ion exchange chromatography to purify a polypeptide with antiproliferative activity against MG-63 human osteosarcoma cells from a proteinaceous extract of antlion. The polypeptide was sequenced and the stability of its antiproliferative activity was tested under a range of conditions in vitro. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the antiproliferative activity of the polypeptide against the MG-63 osteosarcoma cells and MC3T3-E1 mouse calvarial osteoblasts, which were used as a non-neoplastic control. We used western blotting to compare the levels of expression of heat shock transcription factor 1 (HSF1), heat shock protein 90 (HSP90), cyclin-dependent kinase 4 (CDK4), and protein kinase B alpha (ATK1) in MG-63 osteosarcoma cells and their mouse homologs in MC3T3-E1 osteoblasts after their treatment with the antlion antiproliferative polypeptide (ALAPP). Results: The 85-amino-acid ALAPP has a 56% sequence identity with the human heat shock factor binding protein 1 (HSBP1). The antiproliferative activity of the polypeptide is relatively insensitive to temperature, pH, and metal ions. ALAPP has a strong concentration-dependent antiproliferative activity against MG-63 osteosarcoma cells compared with its effect on MC3T3-E1 osteoblasts. ALAPP significantly upregulates the expression of HSF1 in MC3T3-EL osteoblasts, but not in MG-63 osteosarcoma. ALAPP significantly downregulated the expression of HSP90, CDK4, and AKT1 expression in MG-63 osteosarcoma, but not in the osteoblasts. Conclusions: ALAPP has significant antiproliferative activity against MG-63 osteosarcoma cells, but not nonneoplastic MC3T3-E1 osteoblasts. We speculate that non-neoplastic cells may evade the antiproliferative effect of ALAPP by upregulating HSF1 to maintain their HSP90, CDK4, and AKT1 expression at a relatively constant level.

Plasma extracellular vesicle long RNA profiles in the diagnosis and prediction of treatment response for breast cancer.

A large number RNAs are enriched and stable in extracellular vesicles (EVs), and they can reflect their tissue origins and are suitable as liquid biopsy markers for cancer diagnosis and treatment efficacy prediction. In this study, we used extracellular vesicle long RNA (exLR) sequencing to characterize the plasma-derived exLRs from 112 breast cancer patients, 19 benign patients and 41 healthy participants. The different exLRs profiling was found between the breast cancer and non-cancer groups. Thus, we constructed a breast cancer diagnostic signature which showed high accuracy with an area under the curve (AUC) of 0.960 in the training cohort and 0.900 in the validation cohort. The signature was able to identify early stage BC (I/II) with an AUC of 0.940. Integrating the signature with breast imaging could increase the diagnosis accuracy for breast cancer patients. Moreover, we enrolled 58 patients who received neoadjuvant treatment and identified an exLR (exMSMO1), which could distinguish pathological complete response (pCR) patients from non-pCR with an AUC of 0.790. Silencing MSMO1 could significantly enhance the sensitivity of MDA-MB-231 cells to paclitaxel and doxorubicin through modulating mTORC1 signaling pathway. This study demonstrated the value of exLR profiling to provide potential biomarkers for early detection and treatment efficacy prediction of breast cancer.

A new 7-gene survival score assay for pancreatic cancer patient prognosis prediction.

Gene expression features that are valuable for pancreatic ductal adenocarcinoma (PDAC) prognosis are still largely unknown. We aimed to explore pivotal molecular signatures for PDAC progression and establish an efficient survival score to predict PDAC prognosis. Overall, 163 overlapping genes were identified from three statistical methods, including differentially expressed genes (DEGs), coexpression network analysis (WGCNA), and target genes for miRNAs that were significantly related to PDAC patients' overall survival (OS). Then, according to the optimal value of the cross-validation curve (lambda = 0.031), 7 non-zero coefficients (ARNTL2, DSG3, PTPRR, ANLN, S100A14, ANKRD22, and TSPAN7) were selected to establish a prognostic prediction model of PDAC patients. We further confirmed the expression level of 7 genes using RT-PCR, western blot, and immunohistochemistry staining in PDAC patients' tissues. Our results showed that the ROC curve of the 7-mRNA model indicated good predictive ability for 1- and 2-year OS in three datasets (TCGA: 0.71, 0.69; ICGC: 0.8, 0.74; GEO batch: 0.61, 0.7, respectively). The hazard ratio (HR) of the low-risk group had a similar significant result (TCGA: HR = 0.3723; ICGC: HR = 0.2813; GEO batch: HR = 0.4999; all P < 0.001). Furthermore, Log-rank test results in three cohorts showed that the 7-mRNA assay excellently predicted the prognosis and metastasis, especially in TNM stage I&II subgroups of PDAC. In conclusion, the strong validation of our 7-mRNA signature indicates the promising effectiveness of its clinical application, especially in patients with TNM stages I&II.

Autologous tissue reconstruction after mastectomy-A cross-sectional survey of 110 hospitals in China.

BACKGROUND: Autologous reconstruction after mastectomy became more and more popular, so this study aimed to obtain up-to-date and comprehensive data on autologous reconstruction in China. METHODS: An electronic questionnaire was sent to 110 hospitals, which were chosen depending on geographical distribution and hospital types. The questionnaire investigated the demographics, characteristics, breast cancer treatment and reconstruction situation of these hospitals through different modules. We only focused on the autologous breast reconstruction module data. RESULTS: 96 hospitals have performed breast reconstruction surgery. The proportion of the hospital performing latissimus dorsi flap (LDF, N = 91), pedicle transverse rectus abdominis myocutaneous flap (pTRAM, N = 62), free abdominal flap (N = 43) and other kinds of flap decreased in sequence. Of the overall reconstruction cases, only 34.3% were autologous reconstruction and LDF was still the most popular option for autologous reconstruction. Related factors of hospital performing different procedures included years of performing breast reconstruction, breast surgical volume, and establishment of an independent plastic surgery department. Compared with LDF, abdominal breast reconstruction was associated with a higher flap necrosis rate. CONCLUSIONS: This cross-sectional survey offers real-life autologous reconstruction information on a large population and covers the national surgical landscape in China. Autologous reconstruction is still an important part of breast reconstruction. Nevertheless, its low proportion and lower proportion of abdominal flap reconstruction in each institution, demonstrates that special training should be developed for breast surgeons and multidisciplinary cooperation would be promoted in the future.

A nomogram for predicting axillary pathologic complete response in hormone receptor-positive breast cancer with cytologically proven axillary lymph node metastases.

BACKGROUND: The objective of this study was to determine an axillary pathologic complete response (pCR) and its influencing factors in patients with hormone receptor (HR)-positive breast cancer and cytologically proven axillary lymph node metastases. A prediction nomogram was established to provide information for the de-escalation of axillary management in these patients after neoadjuvant chemotherapy. METHODS: The authors retrospectively enrolled all patients with HR-positive breast cancer in the neoadjuvant chemotherapy data set of Fudan University Shanghai Cancer Center. All data were prospectively collected. From 2007 to 2016, 533 consecutive patients were included. Multivariate logistic regression analysis was performed, after which a nomogram was constructed and validated. RESULTS: An axillary pCR was achieved in 168 patients (31.5%), the which was much higher than the proportion of those who achieved a breast pCR (103 patients; 19.3%). Patients who had human epidermal growth factor receptor 2-positive disease (P = .004), a better primary tumor response (P = .001), earlier clinical stage (P = .045), and lower estrogen receptor expression (P < .001) were more likely to achieve a lymph node pCR. The nomogram indicated an area under the receiver operating characteristic curve (AUC) of 0.84 (95% CI, 0.78-0.89) in the training set. The validation set showed good discrimination with an AUC of 0.75 (95% CI, 0.69-0.81). The C-index was 0.834 and 0.756 in the training and validation cohort, respectively. The nomogram was well calibrated. CONCLUSIONS: The authors developed and validated a nomogram for predicting axillary pCR in patients with HR-positive disease accurately by using clinicopathologic factors available before surgery. The model will facilitate logical clinical decision making and clinical trial design.

Hsa_circ_0003159 inhibits gastric cancer progression by regulating miR-223-3p/NDRG1 axis.

BACKGROUND: Abnormally expressed circular RNAs (circRNAs) are implicated in the development and treatment of gastric cancer (GC). Previous study has reported that hsa_circ_0003159 is expressed in GC. However, the role and mechanism of hsa_circ_0003159 in GC progression remain unclear. METHODS: GC tissues and normal tissues were harvested from 55 patients in this study. The levels of hsa_circ_0003159, microRNA (miR)-223-3p and N-myc downstream regulated gene 1 (NDRG1) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation, migration, invasion and apoptosis were determined by cell counting kit (CCK)-8, transwell assay, flow cytometry and western blot, respectively. The target association of miR-223-3p-hsa_circ_0003159 and miR-223-3p-NDRG1 was explored by dual-luciferase reporter assay. Xenograft model was established to assess the roles of hsa_circ_0003159 in GC in vivo. RESULTS: Hsa_circ_0003159 was lowly expressed in GC tissues and cells and mainly presented in the cytoplasm. Low expression of hsa_circ_0003159 was associated with lower overall survival and disease-free survival. Hsa_circ_0003159 overexpression inhibited proliferation, migration and invasion but induced apoptosis in GC cells. MiR-223-3p was a target of hsa_circ_0003159 and abated the effect of hsa_circ_0003159 on proliferation, migration, invasion and apoptosis in GC cells. Hsa_circ_0003159 promoted NDRG1 expression by competitively sponging miR-223-3p. Knockdown of NDRG1 reversed the suppressive effect of hsa_circ_0003159 on GC progression. Besides, hsa_circ_0003159 decreased GC cell xenograft tumor growth by regulating miR-223-3p and NDRG1. CONCLUSION: Hsa_circ_0003159 suppressed proliferation, migration, invasion and xenograft tumor growth but promoted apoptosis by decreasing miR-223-3p and increasing NDRG1 in GC, indicating a novel target for treatment of GC.

Current practice and barriers of mesh-assisted implant-based breast reconstruction in China: A nationwide cross-sectional survey of 110 hospitals.

BACKGROUND: The current National Practice Questionnaire of implant-based breast reconstruction (IBBR) (NPQi) was to assess the clinical practice of mesh-assisted IBBR in China. METHODS: A questionnaire was mailed to 110 hospitals in China, which have more than 200 breast cancer operations performed in 2017. The survey mainly included questions on the type and timing of IBBR, questions about the use of TiLOOP® Bra and acellular dermal matrix (ADM) and the complications of IBBR. RESULTS: IBBR was routinely carried out in 86.36% (95/110) hospitals. IBBR was the most frequently-used (65.7%, 4,296/6,534) BR after mastectomy with a median of 24 cases (IQR 7.5-65) in each hospital. TiLOOP® Bra and ADM were available in 49.5% and 33.7% hospitals, respectively. Hospitals with ADM offered were more likely to located in economically developed regions (65.6%), when compared with hospitals without any mesh offered (14/35, 40.0%, P = 0.036) and with only TiLOOP® Bra offered (16/28, 57.1%, P = 0.032). The surgery volume was largely variated from hospitals without any mesh offered (median 380 cases, IQR 304-550), with only TiLOOP® Bra offered (median 790 cases, IQR 439-1096, P = 0.001) and with ADM offered (median 797 cases, IQR 497-1528, P < 0.001). Higher proportion of one-stage mesh-augmented direct-to-implant BR and lower proportion of autologous BR were observed in hospitals with mesh offered. The reported major complications were similar between hospitals with or without mesh offered. CONCLUSIONS: The NPQi has provided a valuable insight into the current practice of IBBR and mesh used in China. The introduction of mesh-assisted techniques has revolutionized the clinical practice.

CapG promotes resistance to paclitaxel in breast cancer through transactivation of PIK3R1/P50.

Background: Chemotherapy resistance is a major problem in breast cancer treatment and a leading cause of mortality in breast cancer patients. Biomarkers for chemotherapy resistance is under investigation. Methods: Paclitaxel resistant cells were established and subjected to RNA sequencing. Analysis combined with two additional RNA-seq datasets was conducted. CapG expression in patients with adjuvant chemotherapy was studied in breast cancer resection specimens using IHC and related to pathological response and disease-free survival. Paclitaxel resistance was assessed by half-maximal inhibitory concentrations (IC50) and a mouse xenograft model. Results: Increased expression of actin-binding protein CapG strongly correlated with the resistance to paclitaxel chemotherapy and decreased probability to achieve pathological complete response in breast cancer patients. Overexpressing CapG significantly enhanced paclitaxel resistance in breast cancer cells and xenograft tumors. High CapG level also significantly correlated with shorter relapse-free survival as well as hyper-activation of PI3K/Akt signaling in breast cancer patients. Mechanistically, CapG enhanced PIK3R1 expression which led to increased PI3K/Akt activation. Unexpectedly, CapG was found to bind to the variant-specific promoter of PIK3R1/P50 and directly enhance its transcription. We also identified p300/CBP as a transcriptional coregulator of CapG, which is recruited to PIK3R1 promoter through interaction with CapG, thereby increasing PIK3R1/P50 transcription by enhancing histone H3K27 acetylation. Consistently, inhibiting p300/CBP substantially decreased CapG-dependent upregulation of PIK3R1/P50 and subsequent PI3K/Akt activation, resulting in increased sensitivity to paclitaxel treatment in breast cancer cells. Conclusion: High CapG levels may predict poor paclitaxel response in breast cancer patients. Targeting CapG-mediated hyperactivation of PI3K/Akt pathway may mitigate resistance to chemotherapy in breast cancer.

Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999-2017.

OBJECTIVE: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics, management and outcomes of young breast cancer patients over time. METHODS: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and 1999-2015 were identified in the Fudan University Shanghai Cancer Center (FUSCC) and the population-based Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up. RESULTS: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ (DCIS) (from 8.8% to 16.9%; P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort (from 35.3% to 41.9%; P=0.008), whereas it decreased in SEER cohort (from 42.4% to 33.0%; P<0.0001). The percentage of estrogen receptor (ER)-positive cancers was consistently increased in both the invasive ductal carcinoma (IDC) and DCIS patients in the two cohorts. Breast-conserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period. CONCLUSIONS: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial de-escalation in surgical therapies in young breast cancer patients.

LINC00309 is associated with short disease-free survival in breast cancer.

BACKGROUND: Long non-coding RNAs play an important role in breast cancer. Even with adjuvant hormone therapy, patients with estrogen receptor positive breast cancer can present with recurrences and distant metastases. We investigated whether the expression of a novel long non-coding RNA LINC00309 can predict the outcome of breast cancer, especially for hormone-receptor positive patients. METHODS: This retrospective study collected 290 breast cancer patients including 161 patients with hormone-positive. qPCR was performed to detect the expression of LINC00309. Kaplan-Meier and Cox risk proportion model were applied to disclose the function of LINC00309 for breast cancer prognosis. RESULTS: LINC00309 high expression was an independent predictor for worse disease-free survival (HR = 2.127; 95% CI 1.074-4.212; p = 0.030) and associated with a shorter disease-free survival (p = 0.027), especially in hormone-positive breast cancer patients (p = 0.001). Also LINC00309 high expression was associated with a shorter disease-free survival both in selective estrogen receptor modulator related hormone therapy (p = 0.025) and aromatase inhibitors related hormone therapy (p = 0.048). Moreover, LINC00309 was an independent predictor of worse disease-free survival in hormone-receptor positive breast cancer patients on univariate (HR = 4.505; 95% CI 1.722-11.785; p = 0.002) and multivariate (HR = 4.159; 95% CI 1.537-11.251; p = 0.005) analyses. CONCLUSION: In breast cancer, Linc00309 is significantly associated with poor prognosis and may represent a new marker of prognosis.