Progress in application of cyclic single-stranded nucleic acids.

Cyclic nucleic acids are biologically stable against nucleic acid exonucleases due to the absence of 5' and 3' termini. Studies of cyclic nucleic acids mainly focus on cyclic single-stranded nucleic acids. Cyclic single-stranded nucleic acids are further divided into circular RNA (circRNA) and circular single-stranded DNA (cssDNA). The synthesis methods of circRNA include lasso-driven cyclization, intron-paired cyclization, intron cyclization, intron complementary pairing-driven cyclization, RNA-binding protein-driven cyclization, and artificial synthesis depending on the source. Its main role is to participate in gene expression and the treatment of some diseases. Circular single-stranded DNA is mainly synthesized by chemical ligation, template-directed enzyme ligation, and new techniques for the efficient preparation of DNA single loops and topologies based on CircLigase. It is mainly used in rolling circle amplification (RCA) technology and in the bioprotection of circular aptamers and second messengers. This review focuses on the types, synthesis methods, and applications of cyclic single-stranded nucleic acids, providing a reference for further research on cyclic single-stranded nucleic acids.

Targeted axillary dissection after neoadjuvant chemotherapy for highly selective patients with initial cN1 breast cancer: A single-center prospective trial.

BACKGROUND: Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging). METHODS: This prospective trial included patients with initial pre-NAC cT1-3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated. RESULTS: A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30). CONCLUSIONS: In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%. REGISTRATION: chictr.org.cn , ChiCTR2100049093.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial.

Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon's two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898). Eligible female patients aged 18 years or older with histologically confirmed treatment-naïve early TNBC were treated with camrelizumab (200 mg, on day 1), nab-paclitaxel (125 mg/m2, on days 1, 8, and 15), and epirubicin (75 mg/m2, on day 1) every three weeks for six cycles. The primary end point was the pathological complete response; secondary endpoints included safety, objective response rate, and long-term survival outcomes of event-free survival, disease-free survival, and distant disease-free survival. A total of 39 patients were enrolled between January 2020 and October 2021. Twenty-five patients achieved a pathological complete response (64.1%, 95%CI: 47.2, 78.8). The objective response rate was 89.7% (95%CI: 74.8, 96.7), including 35 patients with partial responses. Treatment-related adverse events of grade 3 or 4 occurred in 30 (76.9%) patients. In conclusion, the trial meets the prespecified endpoints showing promising efficacy and manageable safety of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin chemotherapy in female patients with early TNBC. Long-term survival outcomes are still pending.

Enhancing sorption of layered double hydroxide-based magnetic biochar for arsenic and cadmium through optimized preparation protocols.

The impact of multiple preparation protocols on properties and performance of modified biochar remains unclear. This study prepared layered double hydroxide (LDH)-based magnetic biochars (LMBCs) with different LDH loading rates (LLR), pyrolysis temperatures, and biomass sources to explore their performance-characterization relationships toward As(III) and Cd(II). Higher LLR and pyrolysis temperature enhanced LMBCs᾿ adsorption capacities by increasing specific surface area (SSA) and metal/O-containing groups. Hence, LMBC produced at 2:1 LLR (LDH: magnetic biochar) and 800 ℃ pyrolysis exhibited maximum adsorption over 2 times that of LMBC with 0.5:1 LLR and 400 ℃ pyrolysis. Bamboo-sourced LMBC demonstrated superior adsorption than sewage sludge and garlic-sourced LMBCs due to its increased SSA, enabling a higher loading of nano-LDH. Adsorption of As(III) and Cd(II) onto LMBCs was governed by metal-mineral and metal-containing group through co-precipitation and complexation. This study provides a reference for adjusting the preparation protocols to improve sorption performance of modified biochar toward multiple heavy metals.

[Modified Biochar for Remediation of Soil Contaminated with Arsenic and Cadmium: A Review].

Binary pollution of arsenic (As) and cadmium (Cd) has become the main soil environmental problem in China. As an adsorbent or immobilizer, modified biochar is playing an increasing role in the remediation of As and Cd-contaminated soil. Here, the limitations regarding the primitive biochar as an immobilizer for the remediation of As and Cd-contaminated soil were highlighted by this study. Meanwhile, the biochar modification methods for the remediation of As and Cd-contaminated soil were reviewed, and the main interaction mechanisms were analyzed. Finally, the prospects and questions for the future remediation of soil contaminated with As and Cd using modified biochar were proposed. The results showed that metal-modified biochar had a better synergistic effect on the remediation of As and Cd-contaminated soil and thus had better application prospects. The immobilization mechanisms of As and Cd using biochar material remediation were affected by its modification methods. For example, the mechanisms for (non)metal-modified biochar involved the functional group-induced bonding complexation, co-precipitation, and oxyanion As redox; for microorganism-modified biochar, the mechanisms were precipitation and As redox, and those for physical- and acid-modified biochar only included the physical adsorption and weak electrostatic attraction. In view of the limitations of present research on the application of modified biochar for the remediation of As and Cd-contaminated soil, future research is suggested to study the following:① the effect of biomass feedstock type, pyrolysis temperature, preparation conditions, cost, and soil aging; ② evaluation for stability and durability of heavy metal immobilization by modified biochar remediation under different environmental factors; and ③ insight to key remediation mechanisms of As and Cd-contaminated soil by material.

A Nomogram for Identifying HR+/Her2- Breast Cancer Patients with Positive Sentinel Lymph Nodes and Omitted Axillary Lymph Node Dissection Who Need Abemaciclib Therapy.

BACKGROUND The efficacy of abemaciclib in high-risk patients with early-stage HR+/Her2- breast cancer has been verified by MonarchE. However, accurately determining the number of axillary lymph node (ALN) metastases remains challenging. The Z0011 trial changed the axillary management strategy, eliminating the need for axillary lymph node dissection (ALND) in patients with 1-2 sentinel lymph node (SLN) metastases. Therefore, further exploration is needed to identify patients who could benefit from abemaciclib therapy. MATERIAL AND METHODS This retrospective study included cT1-2N0M0 HR+/Her2- patients with 1-2 positive SLNs who underwent ALND. Clinicopathological data were collected, and logistic regression analyses identified independent predictors for ≥4 positive ALNs. A predictive nomogram was developed, and discrimination and calibration were evaluated using the C-index and calibration curve. Clinical efficacy was assessed using decision curve analysis (DCA). RESULTS We enrolled 444 patients, with 77 (17.3%) having ≥4 positive ALNs. Independent predictors for ≥4 positive ALNs included abnormal ALN on ultrasound, mammographic calcifications, T stage, and the number of positive SLNs. The nomogram demonstrated an AUC of 0.777 (95% CI: 0.735-0.815, P<0.001), and internal validation showed good calibration and discrimination (C-index, 0.802; 95% CI: 0.779-0.824). DCA revealed a positive net benefit for risk levels ranging from 5% to 54%. CONCLUSIONS This nomogram is a convenient and reliable tool to predict the risk of ≥4 positive ALNs in HR+/Her2- patients. It aids in protocol selection by identifying SLN-positive patients who may benefit from abemaciclib therapy without ALND.

Ternary Ca-Mg-Al layered double-hydroxides for synergistic remediation of As, Cd, and Pb from both contaminated soil and groundwater: Characteristics, effectiveness, and immobilization mechanisms.

Layered double hydroxides (LDH) are the cost-effective and high-efficiency materials for remediation of potentially toxic elements (PTEs) in contaminated soil and groundwater. Herein, the effectiveness and mechanisms of a ternary Ca-Mg-Al LDH (CMAL) for the synergistic remediation of As, Cd, and Pb were investigated in contaminated soils and simulative groundwaters for the first time. The immobilization efficiencies of As, Cd, and Pb in both black soil (BS) and red soil (RS) amended by CMAL at 5 wt% were all > 75%. CMAL amendment transferred more mobile As, Cd, and Pb fractions in soils to immobile species than did Ca-Al LDH and Mg-Al LDH treatments. Furthermore, using a pump-and-treat technology, 82-98% of these 3 PTEs from contaminated groundwater were successfully immobilized in both CMAL treated BS and RS top-soils. Meanwhile, leaching of Ca, Mg, and Al from CMAL was minimal indicating the material was stable. The excellent immobilization performance of CMAL for these PTEs was attributed to the coating of soil microparticles by CMAL nanosheets that allowed complexation of Ca-O-As/Cd or Mg-O-As/Cd/Pb formation, co-precipitation of Ca/Fe-As and Cd(OH)2, and formation of Ca-bridged ternary complex (FeO-Ca-As/Cd). The adverse effect of oppositive pH/Eh-dependence between As and Cd/Pb was overshadowed by these mechanisms and thus allowed As immobilization. Immobilization of As, Cd, and Pb by CMAL amendment was more favorable for RS soil due to its lower reduction potential and more participation of metal-(hydr)oxides for complexation. Overall, the ternary-LDH is a promising synergistic remediation strategy for multi-PTEs contaminated soil and groundwater.

Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen.

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181−0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554−1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.

Exploration of prognostic factors and the value of adjuvant chemotherapy in T1a,bN0M0 triple-negative breast cancer: a prospective cohort study based on the SEER database.

Background: There are limited published studies on the prognostic predictors and the value of adjuvant chemotherapy (CT) in T1a,bN0M0 triple-negative breast cancer (TNBC) after local therapy. Therefore, the aim of the present study was to explore the prognostic predictors and the value of adjuvant CT in this population. Methods: We identified T1a,bN0M0 TNBC cases registered in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. We analyzed associations between patient characteristics and overall survival (OS) and breast cancer-specific mortality (BCSM), and differences in OS and BCSM in a CT and no chemotherapy (no CT) cohort before and after propensity score matching. Results: Of the 3,065 SEER patients, 1,534 (50.0%) received adjuvant CT. The median follow up was 57 months (interquartile range: 39-75 months). The 5-year OS and cumulative BCSM were 93.6% and 3.3%, respectively. Younger age was not associated with lower OS or higher BCSM in the total and no CT cohorts. Higher histologic grade was associated with lower OS in the no CT cohort, and T1b tumors were associated with higher BCSM in the total cohort. Multivariable analysis showed no association between adjuvant CT and OS or BCSM. Conclusions: Patients with T1a,bN0M0 TNBC had an excellent prognosis with or without adjuvant CT. For this population, higher histologic grade and larger tumor size were predictors of poor prognosis, although the effect of age was complex. Our data did not support using adjuvant CT in patients with T1a,bN0M0 TNBC.

Effect of three aging processes on physicochemical and As(V) adsorption properties of Ce/Mn-modified biochar.

Modified biochar used for soil remediation is affected by exposure to the environment and aging process results in changes in its physicochemical properties and As(V) adsorption and immobilization in soil. Herein, the Ce/Mn-modified wheat straw-biochar (MBC) was manufactured and then aged through three artificial aging processes by exposure to soil with additional natural, freeze-thaw, and dry-wet cycles involved. It revealed that the specific surface areas of freeze-thaw-aged MBC reached 214.98 m2/g and was increased more than those of other two aging treatments. In addition, the pH values and C contents of MBC all decreased after aging while the H and O contents increased. Correspondingly, the contents of O-containing functional groups like C-O, -OH, and CO all increased by >16% with aging. The freeze-thaw cycling and alternating dry-wet aging treatments improved adsorption capacities of As(V) onto MBC and were increased by 16.2 and 10.6% at pH 5, respectively and these samples exhibited the best recyclability and adsorption selectivity for As(V). However, natural aging exerted a lower effect for As(V) adsorption by MBC due to its few changes on physicochemical properties. Causally, the freeze-thaw and dry-wet aging activated the Ce/Mn-oxides to generate Mn2+/3+ species and a new mono-Ce that exerted a strong bonding complexation with As(V) to form Ce/Mn-O-As ligands and increased CeAsO4 precipitation. Our results offer a new insight into the alterations expected for modified biochars with aging treatment in terms of As(V) adsorption for its long-term utilization in As contaminated soil.

Phosphorus-modified biochar cross-linked Mg-Al layered double-hydroxide stabilizer reduced U and Pb uptake by Indian mustard (Brassica juncea L.) in uranium contaminated soil.

The decommissioning of uranium tailings (UMT) is usually accompanied by uranium (U) contamination in soil, which poses a serious threat to human health and ecological security. Therefore, the remediation of uranium pollution in soil is imminent from ecological and environmental points of view. In recent years, the use of biochar stabilizers to repair uranium tailings (UMT) soil has become a research hotspot. In this study, a novel phosphorus-modified bamboo biochar (PBC) cross-linked Mg-Al layered double-hydroxide composite (PBC@LDH) was prepared. The hyperaccumulator plant Indian mustard (Brassica juncea L.) was selected as the test plant for outdoor pot experiments, and the stabilizers were added to the UMT soil at the dosage ratio of 15 g kg-1, which verified the bioconcentrate and translocate of U and associated heavy metal Pb in the UMT soil by Indian mustard after stabilizer remediated. The results shown that, after 50 days of growth, compared with the untreated sample (CK), the Indian mustard in PBC@LDH treatment possessed a better growth and its biomass weight of whole plant was increased by 52.7%. Meanwhile, the bioconcentration factors (BF) of U and Pb for PBC@LDH treatment were significantly decreased by 73.4% and 34.2%, respectively; and the translocation factors (TF) were also commendable reduced by 15.1% and 2.4%, respectively. Furthermore, the Tessier available forms of U and Pb in rhizosphere soil showed a remarkably decrease compared with CK, which reached by 55.97% and 14.1% after PBC@LDH stabilization, respectively. Complexation, precipitation, and reduction of functional groups released by PBC@LDH with U and Pb described the immobilization mechanisms of biochar stabilizer preventing U and Pb enrichment in Indian mustard. As well as, the formation of U-containing vesicles was prevented by the precipitation of -OH functional groups with free U and Pb ions around the cell tissue fluids and vascular bundle structure of plant roots, thereby reducing the migration risk of toxic heavy metals to above-ground parts. In conclusion, this research demonstrates that the PBC@LDH stabilizer offers a potentially effective amendment for the remediation of U contaminated soil.

[Effects of Earthworms/Biochar on Bacterial Diversity and Community in As-contaminated Red Soil].

Cerium-manganese modified biochar (MBC) combined with earthworms (Eisenia foetida) can immobilize arsenic (As) in red soils. In this study, high-throughput sequencing technology was used to explore the combined effects of MBC and E. foetida on bacterial diversity and community structure in As-contaminated red soils. The results showed that the single earthworm treatment had the highest diversity index, whereas the diversity index decreased in the single biochar or MBC treatment, indicating that earthworms can boost the growth of bacteria in the soil, and the addition of biochar/MBC all decreased the bacterial diversity of soils. When biochar/MBC was combined with earthworms, the diversity index increased to some degree. In terms of bacterial community structure, the relative abundance of Proteobacteria and Bacteroidetes increased significantly in each treatment, especially for MBC-earthworm treated soil, in which the relative abundance was increased by 17.08% and 329.47% for Proteobacteria and Bacteroidetes, respectively, compared to that in the control (CK). Otherwise, those abundances were decreased by 19.18% and 48.76%, respectively, for Acidobacteria and Chloroflexi. Correlation analysis results showed that the soil water-soluble As (WSAs) was negatively correlated with the relative abundances of Proteobacteria and Bacteroides (P<0.05) but was positively correlated with Acidobacteria and Chloroflexi (P<0.05), which indicated that with the decrease in WSAs in soils, the bacteria of Proteobacteria and Bacteroides reproduced rapidly, whereas the Acidobacteria and Chloroflexi were inhibited. Moreover, different treatments induced selective changes in the bacterial community, in which earthworms significantly promoted the proliferation of γ-Proteobacteria, Flavobacteriales, Aeromonadales, and Variovorax and earthworms improved the immobilization effect of As by promoting the growth of these bacteria.

Pre-magnetic bamboo biochar cross-linked CaMgAl layered double-hydroxide composite: High-efficiency removal of As(III) and Cd(II) from aqueous solutions and insight into the mechanism of simultaneous purification.

Trivalent arsenic (As(III)) and divalent cadmium (Cd(II)) contamination in water environment is an urgent issue because of their most toxic physicochemical properties. Herein, the simultaneous purification of As(III) and Cd(II) from aqueous solution was achieved by use of a pre-magnetic Fe modified bamboo biochar that cross-linked CaMgAl layered double-hydroxide composite (Fe-BC@LDH). In a binary system, adsorption equilibrium of As(III) and Cd(II) onto specific sorbent Fe-BC@LDH was reached within 100 and 10 min of contact time under anaerobic conditions, respectively, and the maximum adsorption capacities of As(III) and Cd(II) by Fe-BC@LDH were respectively calculated to be ⁓265.3 and ⁓320.7 mg/g at pH 4.5 and 5- and 14-times than that of unmodified biochar. Moreover, adsorption in a competitive or single system, the sorbent displayed a greater preference for Cd(II). Importantly, the removal of As(III) and Cd(II) onto the composite was more favorable in a binary system due to formation of ternary FeOCdAs bonding configuration as well as the redox transformation of As(III) to As(V), inner-sphere complexation of MOAs/Cd (MFe, Ca, Mg, Al), electrostatic attraction, and co-precipitation of scorodite and hydroxy­iron­cadmium. Furthermore, the nanocomposite was still highly efficient after 5 adsorption cycles. This study demonstrated that the synthesized cost-effective Fe-BC@LDH is a promising candidate for the simultaneous separation of As(III) and Cd(II) from wastewater.

Effect of the HER-2/CEP17 ratio in IHC 2+/FISH-amplified breast cancer on pathological complete response to neoadjuvant pertuzumab and trastuzumab treatment-a retrospective cohort study.

Background: Human epidermal growth factor receptor-2 (HER-2) protein expression level could serve as a predictor of pathological complete response (pCR) to neoadjuvant trastuzumab-containing regimens. The aim of the present study was to evaluate whether pCR to neoadjuvant trastuzumab and pertuzumab treatment is dependent on the level of the HER-2/CEP17 (chromosome enumeration probe 17) ratio in immunohistochemistry (IHC) 2+/fluorescence in situ hybridization (FISH)-amplified breast cancer. Methods: Patients with primary IHC 2+/FISH-amplified breast cancer who underwent neoadjuvant anti-HER-2 dual-targeted therapies were retrospectively included between January 1, 2020 and May 30, 2021. The primary predictive variable was HER-2/CEP17 ratio, and the primary outcome variable was pCR. Other variables consisted of age, menopausal status, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PgR), and Ki-67. Association between clinicopathologic variables and pCR was evaluated using the chi-square test and logistic regression analysis. Results: The median age of the patients was 51.78 years (25-67 years), and 50.7% of the patients were in the premenopausal stage. The clinical stage at diagnosis was Stage III in 38 patients (55.1%). Of all patients, 40.6% patients were estrogen receptor positive, and 75.4% patients had a Ki-67 index of ≥30%. The overall pCR (ypN0/isypN0) rate was 31.9%. Patients with HER-2/CEP17 ratio ≥6.0 had a pCR rate of 55.0%, it was statistically higher than 22.4% in patients with HER-2/CEP17 ratio <6.0. Logistic regression analysis confirmed the independent association between HER-2/CEP17 ratio and pCR (P=0.020, OR: 5.203, 95% CI: 1.302-20.783). Conclusions: A HER-2/CEP17 ratio ≥6.0 might be related to more achievement of pCR in the neoadjuvant anti-HER-2 dual-targeted therapies. Further studies are needed to validate the finding.

Establishment and Verification of a Predictive Model for Node Pathological Complete Response After Neoadjuvant Chemotherapy for Initial Node Positive Early Breast Cancer.

OBJECTIVE: Axillary node status after neoadjuvant chemotherapy (NCT) in early breast cancer patients influences the axillary surgical staging procedure. This study was conducted for the identification of the likelihood of patients being node pathological complete response (pCR) post NCT. We aimed to recognize patients most likely to benefit from sentinel lymph node biopsy (SLNB) following NCT and to reduce the risk of missed detection of positive lymph nodes through the construction and validation of a clinical preoperative scoring prediction model. METHODS: The existing data (from March 2010 to December 2018) of the Chinese Society of Clinical Oncology Breast Cancer Database (CSCO-BC) was used to evaluate the independent related factors of node pCR after NCT by Binary Logistic Regression analysis. A predictive model was established according to the score of considerable factors to identify ypN0. Model performance was confirmed in a cohort of NCT patients treated between January 2019 and December 2019 in Henan Cancer Hospital, and model discrimination was evaluated via assessing the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Multivariate regression analysis showed that the node stage before chemotherapy, the expression level of Ki-67, biologic subtype, and breast pCR were all independent related factors of ypN0 after chemotherapy. According to the transformation and summation of odds ratio (OR) values of each variable, the scoring system model was constructed with a total score of 1-5. The AUC for the ROC curves was 0.715 and 0.770 for the training and the validation set accordingly. CONCLUSIONS: A model was established and verified for predicting ypN0 after chemotherapy in newly diagnosed cN+ patients and the model had good accuracy and efficacy. The underlined effective model can suggest axillary surgical planning, and reduce the risk of missing positive lymph nodes by SLNB after NCT. It has great value for identifying initial cN+ patients who are more appropriate for SLNB post-chemotherapy.

Nomogram for Predicting Overall Survival and Assessing the Survival Benefit of Adjuvant Treatment in pT1-2N0M0 Triple-Negative Breast Cancer: A Surveillance, Epidemiology, and End Results-Based Study.

Background: Accurate survival prediction of triple-negative breast cancer (TNBC) is essential in the decision-making of adjuvant treatment. The aim of this prospective study was to develop a nomogram that predicts overall survival and assists adjuvant treatment formulation. Methods: A total of 16,977 patients with pT1-2N0M0 TNBC between 2010 and 2015 from the SEER database were enrolled. Independent prognostic factors associated with overall survival (OS) were identified using univariate and multivariate Cox regression hazards method and utilized to compose the nomogram. The survival benefit of adjuvant treatment on OS were analyzed after stratification by nomogram sum-score. Results: Patients were randomized 7:3 into the training and validation cohorts. Multivariate analysis revealed that age at diagnosis, grade, tumor size, laterality, and mastectomy type were independent prognostic factors of OS and were integrated to develop a nomogram for predicting prognosis. Patients were stratified into 3 prognostic subgroups according to the sum-score of our nomogram. There were no significant differences found in OS between surgery alone and other adjuvant treatment strategies in low risk group. In moderate risk group, patients receiving chemotherapy or the combination of chemotherapy and radiotherapy showed better OS than those receiving surgery alone or radiotherapy alone. For patients in high risk group, the combination of chemotherapy and radiotherapy could maximally improve the overall survival rate of patients. Conclusion: A novel nomogram for OS prediction and risk stratification in patients with pT1-2N0M0 TNBC was developed. This cohort study reveals the prognostic roles of different adjuvant treatment strategies in subgroups, which may provide a reference for the decision-making of postoperative treatment, eventually improving prognosis for individual patients.

Long non coding RNA NRON inhibited breast cancer development through regulating miR-302b/SRSF2 axis.

AIMS: Long noncoding RNA NRON has been investigated in various tumors, such as hepatocellular carcinoma. However, the role of lncRNA NRON in breast cancer remains unclear. The aim of this study was to explore the function and mechanism of lncRNA NRON in breast cancer. MATERIALS AND METHODS: Overexpression and knockdown vectors were constructed. Proliferation and invasion were measured to evaluate the function of lncRNA NRON. A dual-luciferase reporter assay was utilized to analyze the potential binding target of lncRNA NRON. A rescue experiment was performed to verify the relationship between lncRNA NRON and SRSF2. RESULTS: Our results showed that the expression of lncRNA NRON was significantly downregulated in breast cancer tissues. Overexpression of lncRNA NRON significantly inhibited proliferation and invasion in breast cancer cell lines. Knockdown of lncRNA NRON promoted breast cancer development. We also provided evidence that lncRNA NRON negatively regulated miR-302b. Moreover, we identified SRSF2 as a downstream target of miR-302b. CONCLUSION: Overall, we performed a comprehensive analysis to indicate that the lncRNA NRON/miR-302b/SRSF2 axis plays an important role in breast cancer. Our study is the first to prove that lncRNA NRON functions as a tumor suppressor in breast cancer.