R-loop-dependent promoter-proximal termination ensures genome stability.

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.

Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial.

BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

HER2-low heterogeneity between primary and paired recurrent/metastatic breast cancer: Implications in treatment and prognosis.

BACKGROUND: With the largest sample size to date, the authors' objective was to investigate the incidence of primary-to-metastatic human epidermal growth factor 2 (HER2) conversion and the predictors for such conversion. Moreover, no previous studies have evaluated the prognosis of patients who have negative HER2 expression (HER2-0) versus low HER2 expression (HER2-low) when HER2 status was assessed based on all recurrent/metastatic lesions. METHODS: The authors included 1299 patients who had available HER2 status of primary breast tumors and paired recurrent/metastatic lesions at Fudan University Shanghai Cancer Center and West China Hospital. RESULTS: In total, 370 patients (28.5%) experienced primary-to-metastatic HER2 conversion. Intrapatient intermetastasis spatial heterogeneity and temporal heterogeneity of HER2 were detected. When assessing HER2 based on recurrent/metastatic tumors, patients who had HER2-0 tumors had significantly shorter overall survival than those who had HER2-low tumors in the overall population and in the estrogen receptor (ER)-negative subgroup. However, when assessing HER2 based on primary tumors, there was no difference in overall survival between patients who had HER2-0 versus HER2-low tumors. Moreover, patients who had tumors that converted from HER2-0 to HER2-low had longer overall survival than those who had consistent HER2-0 status in the ER-negative subgroup. By combining four predictors (ER status, Ki67 index, biopsy site, and disease-free interval), the authors established the first prediction tool to estimate the probability of HER2-0 tumors converting to HER2-low/positive tumors. CONCLUSIONS: Intrapatient primary-to-metastatic and intermetastatic HER2 heterogeneity were observed in this large-scale cohort study. When evaluating HER2 based on recurrent/metastatic tumors, an overall survival difference was observed between patients who had HER2-0 versus HER2-low, recurrent/metastatic breast tumors. The developed prediction tool might help clinicians screen out patients with primary HER2-0 tumors that have a high probability of HER2 status conversion and recommend them for re-biopsy, thus helping to screen out candidate patients for trastuzumab deruxtecan treatment.

Effects of microplastics on typical macrobenthos in sargassum ecosystems.

Recently, microplastics (MPs) have attracted extensive attention to their wide distribution and potential toxicity in ecosystems. However, there was a lack of research focused on MPs in seaweed bed ecosystems. This study investigated the distribution and toxicity of MPs in macrobenthos in Sargassum ecosystem. According to the in-situ investigation results, the abundance of MPs in the sediment was 0.9-2.3 items/g, the indoor microcosmic experiment was constructed. After exposure to MPs (0, 2, and 20 items/g) for 30 days, the abundance of MPs in macrobenthos exhibits a concentration-dependent increase. However, there was no significant bioaccumulation of MPs at the trophic level. The indoor toxicity test revealed that MPs induced oxidative stress and altered intestinal microflora composition in macrobenthos, even at actual environmental concentrations (2 items/g). It may result in a perturbation of the organism's homeostatic equilibrium. High-concentration (20 items/g) MPs had a greater impact on alkaline phosphatase (AKP) in Mollusks. The increase in AKP activity could be indicative of an adaptive mechanism in some macrobenthos while the decline in AKP activity might signal a decrease in their survival. These results elucidated the fate of MPs in ecosystem and the ecological risks of MPs to large benthic animals on model environmental conditions.

A prospective comparison of a modified miniaturised hand-held epifluorescence microscope and touch imprint cytology for evaluation of axillary sentinel lymph nodes intraoperatively in breast cancer patients.

BACKGROUND: The management of axillary lymph nodes in early-stage breast cancer patients has changed considerably, with the primary focus shifting from the examination of sentinel lymph nodes (SLNs) to toward the detection of all macro-metastases. However, current methods, such as touch imprint cytology (TIC) and frozen sections, are inadequate for clinical needs. To address this issue, we proposed a novel miniaturised epifluorescence widefield microscope (MEW-M) to assess SLN status intraoperatively for improved diagnostic efficiency. METHODS: A prospective, side-by-side comparison of intraoperative SLN evaluation between MEW-M and TIC was performed. RESULTS: A total of 73 patients with 319 SLNs consecutive enrolled in this study. MEW-M showed significantly superior image quality compared to TIC (median score 3.1 vs 2.1, p < 0.0001) and had a shorter time to issue results (10.3 vs 19.4 min, p < 0.0001). Likelihood ratio analysis illustrated that the positive likelihood ratio value of MEW-M compared with TIC was infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 1 (classifying results into negative/positive), infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 2 (classifying results into macro-metastasis/others, and TIC results followed the same classification as model 1), respectively. Similarly, the negative likelihood ratio values of MEW-M compared with TIC were 0.055 (95% CI, 0.018-0.160) and 0.074 (95% CI, 0.029-0.190) in model 1; and 0.019 (95% CI, 0.003-0.130) vs 0.020 (95% CI, 0.003-0.140) in model 2, respectively. CONCLUSIONS: MEW-M is a promising technique that can be utilised to provide a rapid and accurate intraoperative assessment of SLN in a clinical setting to help improve decision-making in axillary surgery.

Patient-Reported Outcomes and Complication Profiles of Implant-Based Breast Reconstruction in Patients With Postmastectomy Radiation Therapy.

OBJECTIVE: This study aims to investigate the patient-reported outcomes (PROs) and complications of distinct implant-based breast reconstruction modality for patients with postmastectomy radiation therapy (PMRT). METHODS: A retrospective review was conducted on breast cancer patients with stage II-III disease who performed implant-based breast reconstruction following with PMRT between September 2016 and April 2022. The patients were categorized into two matched groups: (1) patients receiving prepectoral breast reconstruction (PBR) or (2) subpectoral breast reconstruction (SBR) followed by PMRT. Following reconstruction, the patients were further compared for PMRT with the tissue expander (PMRT-TE) versus PMRT with permanent implant (PMRT-PI). PROs were measured with BREAST-Q questionnaire. Early and late complications were recorded and analyzed. RESULTS: A total of 55 eligible patients were recruited. Patients who underwent PBR reported significantly higher satisfaction with breasts scores (P = 0.003) compared with the SBR group. The PMRT-TE group had higher satisfaction with breasts (P = 0.001) but lower physical well-being (P = 0.029) scores compared with PMRT-PI group. Moreover, patients in SBR cohort had a higher risk of capsular contracture (Baker grade III or IV) (20.5% vs 6.3%) and implant dislocation (48.7% vs 12.5%) than patients in PBR cohort. Patients in PMRT-PI group had a slightly higher rate of capsular contracture (Baker grade III or IV) than PMRT-TE group (20.8% vs 12.9%). CONCLUSIONS: PBR was associated with lower rates of late complications, especially for implant dislocation, and higher satisfaction with breasts scores compared to SBR. In addition, compared to PMRT-TE with PMRT-PI, patients in PMRT-TE cohort reported superior PROs of satisfaction with breasts.

Laser hemorrhoidoplasty vs. rubber band ligation: a randomized trial comparing 2 mini-invasive treatment for grade II hemorrhoids.

PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.

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.

Leaky-Vivaldi antenna covered with metasurface with leaky wave radiation and aperture radiation.

A leaky-Vivaldi antenna covered with metasurface (LVAM) is proposed in this paper. The traditional Vivaldi antenna covered with metasurface realizes backward frequency beam-scanning from -41∘ to 0∘ in the high-frequency operating band (HFOB) and retains aperture radiation in the low-frequency operating band (LFOB). In the LFOB, the metasurface can be regarded as a transmission line to realize a slow-wave transmission. In the HFOB, the metasurface can be considered a 2D periodic leaky-wave structure to realize a fast-wave transmission. The simulated results show that LVAM has the -10 dB return loss bandwidths of 46.5% and 40.0%, and the realized gain of 8.8-9.6 dBi and 11.8-15.2 dBi cover the 5 G Sub-6 GHz band (3.3-5.3 GHz) and the X band (8.0-12.0 GHz), respectively. The test results are in good agreement with the simulated results. As a dual-band antenna covering the 5 G Sub-6 GHz communication band and military radar band, the proposed antenna can guide the future integrated design of communication and radar antenna systems.

Young age is associated with inferior outcomes in early-stage luminal B breast cancer patients who undergo mastectomy.

Aim: This retrospective study aimed to evaluate the effect of age on cancer relapse and survival in breast cancer patients undergoing different treatments. Methods: The propensity score method was used to correct for disparities between two groups; 2049 young patients were matched to 4053 older patients. Kaplan-Meier curves and Cox proportional hazards models were used to assess disease-free survival. Results: In the original cohort, young patients showed higher lymph node metastasis, hormone-receptor positivity and high Ki-67 levels. After propensity score matching, the disease-free survival of young patients with the luminal B-like subtype who received mastectomy with early stage disease exhibited inferior survival. Conclusion: Decisions about biology-driven systemic treatment strategies for young patients are worthy of discussion with a multidisciplinary tumor board.

Buffer zone-based trace elements indicating the impact of human activities on karst urban groundwater.

The tanglesome allocation of landscape types at various spatial dimensions is an important component influencing the quality of groundwater environment in karst cities. Trace elements can be used as indicators of the extent of impact on groundwater which is an effective means of tracing groundwater contamination. In this study, we studied the influence of landscape patterns on trace elements in groundwater of typical karst cities in Southwest China (Guiyang City) on a multi-spatial scale by using multivariate statistical analysis. According to the sampling points, buffer zone scales with different radii (500 m, 1000 m, 1500 m, and 4000 m) were established to quantify the land use model. There are suburban and urban differences in trace element content. The city center has higher levels of trace elements compared to suburban areas, especially Li, Ni, Tl, Cu, Sr, Co, As, and Mn. In addition, the outcomes of the multiple linear regression had shown that the size effect of the association from landscape pattern to trace elements varies with different indicators and parameters. The results of redundancy analysis showed an overall change in trace elements was better interpreted by the landscape pattern of the 1500 m-scale buffer. At the same time, at the 1500 m scale, Ni, Tl, Cu, Co, As, Cr, Sr, Li, and Mn were positively correlated with the urban landscape index (4LPI, 4LSI), influenced by urban anthropogenic activities, while Cd, Zn, and Pb were positively correlated with the cropland landscape index (1AI, 1LPI), influenced by agricultural activities. This study indicates that trace elements are a reliable indicator for tracing groundwater contamination. The buffer zone can reflect the extent of urban impacts on groundwater and provide a new and effective analytical tool for groundwater management.

Effects of Traditional Chinese Medicine on Serum Cytokines for the Dampness-heat Syndrome of Ulcerative Colitis: A Systematic Review and Meta-analysis.

Context: Ulcerative colitis (UC) is a chronic disease affecting the large intestine. Cytokines, as inflammatory mediators, can enable pathological injury of the intestinal mucosa and play an important role in UC's pathogenesis. Traditional Chinese medicine (TCM) offers a wealth of theory and experience in UC's treatment. Objective: The literature review and meta-analysis intended to examine TCM's effects in the treatment of UC patients who have the dampness-heat syndrome on the serum cytokines known to be related to UC's pathogenesis. Design: The research team conducted a comprehensive literature search for randomized controlled trials (RCTs) in seven databases. The search covered all publicly published documents from the establishment of a database until August 31, 2021. The team also performed a meta-analysis of the RCTs' results to compare the levels of cytokines in the intervention and control groups. Setting: The study took place at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University of Traditional Chinese Medicine in Shanghai, China. Interventions: For the meta-analysis, the research team created two intervention groups, the oral TCM only group and the TCM+ Western Medicine (WM) group and a control group, the WM group. The team determined which RCT's measured a particular cytokine and which groups those RCTs compared, the team examined the differences between the groups postintervention. Outcome Measures: The primary outcome measures were the RCTs' levels of 13 serum cytokines-interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), IL-17, IL-23, interferon-gamma (IFN-γ), IL-21, IL-1, IL-1ß, IL-2, IL-4, IL-10, and IL-13. The team used the random effects model to combine the results for the serum markers as standardized mean differences (SMDs) and compared the two intervention groups to the control group. Results: The research team identified 22 studies that included 1957 participants. The team found that six proinflammatory cytokines were significantly lower in the combined TCM only and TCM+WM intervention groups than in the WM control group: (1) IL-6-SMD -2.60, 95%CI -3.37 to -1.83, P < .00001; (2) IL-8-SMD -2.49, 95%CI -3.34 to -1.64, P < .00001; (3) TNF-α-SMD -1.70, 95%CI -2.07 to -1.33, P < .00001; (4) IL-17 (TCM+WM group only)-SMD-2.99, 95%CI -4.66 to -1.31, P = .0005; (5) IL-23 (TCM+WM group only)-SMD -2.43, 95% CI -2.78 to -2.08, P < .00001; and (6) IFN-γ-SMD -1.47, 95% CI -1.81 to -1.12, P < .00001. The team found that two anti-inflammatory cytokines were significantly higher in the intervention group than in the control group: (1) IL-4-SMD 1.45, 95% CI 0.92-1.99, P < .00001, and (2) IL-10-SMD 1.33, 95% CI 0.97-1.69, P < .00001. For the results that the team couldn't combine, the levels of the proinflammatory cytokines IL-1, IL-1ß, IL-2, and IL-21 were significantly lower in the combined intervention groups than in the control group (P < .05), and the level of the anti-inflammatory cytokine IL-13 in the intervention group was significantly higher than that in the control group (P < .05). The comprehensive analysis showed that oral TCM or a combination of TCM and WM could more significantly reduce the levels of the proinflammatory cytokines IL-6, IL-8, TNF-α, IL-17, IL-23, IFN-γ, IL-21, IL-1, IL-1ß and IL-2 and increase the levels of the anti-inflammatory cytokines IL-4, IL-10 and IL-13. Conclusions: Oral TCM or TCM+WM can reduce the proinflammatory response and increase the anti-inflammatory response of UC patients by regulating serum cytokines and can obtain a better clinical effect than WM only. These benefits can alleviate intestinal inflammation in patients and have a positive effect on clinical efficacy. In the future, more high-quality, large-sample, and long-term follow-up randomized controlled trial are necessary to support research analysis.

An effective and considerable treatment of pilonidal sinus disease by laser ablation.

The treatment of sacrococcygeal pilonidal disease (SPD) is still challenging. Although many non-surgical and surgical methods exist, no consensus has been reached on the best treatment. This study aimed to evaluate the efficacy of laser ablation using 1470-nm radial diode laser fiber in treating SPD. We retrospectively studied the data of our 48 patients who operated on this technique between March 2019 and July 2022. All patients were treated with laser ablation using 1470-nm radial diode laser fiber. The healing rate and recurrence rate, demographic and surgical data, postoperative pain, complications (wound infection, wound bleeding), the time of returning to regular work and life, and the time of wound healing were recorded. Postoperative pain was measured based on the visual analog scale (VAS) score. Postoperative follow-up was performed in the outpatient clinic every 1 week for 1 month. Among the 48 patients, 41 males and 7 females, with a mean age of 27.7 years (range 14-42), the healing rate was 100%, and the average healing time was 28.3 ± 5.5 days. Mean operative time was 15.5 ± 3.3 min. The recurrence rate was 2.1%. One patient relapsed 3 months after the operation. The patient underwent laser ablation again, and the sinus tract was closed. The median visual analog scale (VAS) score on the day of operation was 0(0,2). The median VAS score on the first, third, seventh, and fourteenth day after operation was 0(0,2), 0(0,1), 0(0,1), and 0(0,0), respectively. There was no wound infection or bleeding after the operation. The mean time to normal work/life was 7.1 ± 3.2 days. Almost all the patients felt very satisfied with the operation. Laser ablation using 1470-nm radial diode laser fiber is effective in SPD treatment. It is associated with minor wounds and mild postoperative pain. It is a simple, safe, and minimally invasive technique and its clinical application for acute and chronic SPD in the absence of abscess is promising.

Immediate Breast Reconstruction After Neoadjuvant Chemotherapy: Factors Associated With Surgical Selection and Complications.

BACKGROUND: Breast reconstruction has become an integral component of breast cancer treatment, especially for patients who are unable to undergo breast-conserving surgery after neoadjuvant chemotherapy (NAC). We analyzed factors influencing the type of immediate reconstruction surgery after NAC, as well as the complication rates for each surgery type. METHODS: The study included patients with breast cancer who underwent mastectomy following NAC from 2010 to 2021. Clinicopathological characteristics, unplanned reoperation rates, and the duration of postoperative hospitalization were analyzed in patients undergoing autologous tissue reconstruction (ATR, n = 127), implant-based reconstruction (IBR, n = 60), and combined autologous tissue and implant reconstruction (n = 60). RESULTS: A total of 1651 patients who received NAC before mastectomy were enrolled. Among them, 247 (15.0%) patients underwent immediate reconstruction (IR), whereas 1404 underwent mastectomy only. Patients in the IR group were younger ( P < 0.001), had lower body mass index ( P < 0.001), and exhibited earlier clinical ( P = 0.003) and nodal ( P < 0.001) stage than those in the non-IR group. Patients in the ATR group were older ( P < 0.001) and had higher body mass index ( P = 0.007), larger tumor size ( P = 0.024), and more frequent childbearing history ( P = 0.011) than those in the other groups. Complications resulting in unplanned reoperations were more frequent in the IBR group ( P = 0.039). The duration of postoperative hospitalization was longest after ATR ( P = 0.008). CONCLUSIONS: Age and clinical tumor/nodal stage at presentation are associated with IR for patients undergoing mastectomy after NAC. For patients undergoing IR after NAC, ATR may be safer and more suitable than IBR.

MNX1 Promotes Anti-HER2 Therapy Sensitivity via Transcriptional Regulation of CD-M6PR in HER2-Positive Breast Cancer.

Although targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly prolonged survival time and improved patients' quality of life, drug resistance has gradually emerged. This study explored the mechanisms underlying the effect of the motor neuron and pancreatic homeobox 1 (MNX1) genes on drug sensitivity in HER2-positive breast cancer. From July 2017 to 2018, core needle biopsies of HER2-positive breast cancer were collected from patients who received paclitaxel, carboplatin, and trastuzumab neoadjuvant therapy at our center. Based on treatment efficacy, 81 patients were divided into pathological complete response (pCR) and non-pCR groups. High-throughput RNA sequencing results were analyzed along with the GSE181574 dataset. MNX1 was significantly upregulated in the pCR group compared with the non-pCR group in both sequencing datasets, suggesting that MNX1 might be correlated with drug sensitivity in HER2-positive breast cancer. Meanwhile, tissue array results revealed that high MNX1 expression corresponded to a good prognosis. In vitro functional tests showed that upregulation of MNX1 significantly increased the sensitivity of HER2-positive breast cancer cells to lapatinib and pyrotinib. In conclusion, MNX1 may serve as a prognostic marker for patients with HER2-positive breast cancer, and its expression may facilitate clinical screening of patients sensitive to anti-HER2-targeted therapy.

Omission of axillary surgery for ipsilateral breast tumor recurrence with negative nodes after previous breast-conserving surgery: is it oncologically safe?

PURPOSE: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR. METHODS: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS) from 2010 to 2018. Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between the SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups. RESULTS: A total of 154 IBTR patients were eligible for final analysis. Compared to the no SAS group, SAS group was less likely to undergo ALND (15.1 vs 73.3%, p < 0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p = 0.03), and were more likely to have discordant molecular subtype (35.8 vs 12.9%, p = 0.001) and different quadrant location (37.7 vs 19.8%, p = 0.02) with primary tumor. However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. No significant differences were observed in LRRFS, DMFS or OS between the two groups. CONCLUSION: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS but comparable LRRFS, DMFS, and OS. These results support a wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND.

Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial.

BACKGROUND: Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine has survival benefits and acceptable tolerability in patients with HER2-positive metastatic breast cancer. We further assessed addition of pyrotinib to trastuzumab and docetaxel in the neoadjuvant setting. METHODS: In this multicenter, double-blind, phase 3 study (PHEDRA), treatment-naive women with HER2-positive early or locally advanced breast cancer were randomly assigned (1:1) to receive four neoadjuvant cycles of oral pyrotinib or placebo (400 mg) once daily, plus intravenous trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg) and docetaxel (100 mg/m2) every 3 weeks. The primary endpoint was the total pathological complete response (tpCR; ypT0/is and ypN0) rate per independent central review. RESULTS: Between Jul 23, 2018, and Jan 8, 2021, 355 patients were randomly assigned, 178 to the pyrotinib group and 177 to the placebo group. The majority of patients completed four cycles of neoadjuvant treatment as planned (92.7% and 97.7% in the pyrotinib and placebo groups, respectively). The tpCR rate was 41.0% (95% CI 34.0 to 48.4) in the pyrotinib group compared with 22.0% (95% CI 16.6 to 28.7) in the placebo group (difference, 19.0% [95% CI 9.5 to 28.4]; one-sided P < 0.0001). The objective response rate per investigator was 91.6% (95% CI 86.6 to 94.8) in the pyrotinib group and 81.9% (95% CI 75.6 to 86.9) in the placebo group after the neoadjuvant treatment, resulting in an increase of 9.7% (95% CI 2.7 to 16.6). The most common grade 3 or worse adverse events were diarrhea (79 [44.4%] in the pyrotinib group and nine [5.1%] in the placebo group), neutropenia (33 [18.5%] and 36 [20.3%]), and decreased white blood cell count (29 [16.3%] and 24 [13.6%]). No deaths were reported during neoadjuvant treatment. CONCLUSIONS: The primary endpoint of the study was met. Neoadjuvant pyrotinib, trastuzumab, and docetaxel significantly improved the tpCR rate compared with placebo, trastuzumab, and docetaxel, with manageable toxicity, providing a new option for HER2-positive early or locally advanced breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03588091.

Low-profile and wide-band RCS-reduction antenna array based on the metasurface polarization converter.

Antenna elements with a low profile and high front-to-back (FB) ratio mean that no additional reflective cavity is required when forming the array, which greatly helps to simplify and lighten the entire array system. In this paper, we enhance the FB ratio of the antenna to 35 dB while maintaining an ultra-low profile of 0.05 λ0 by attaching the broadband polarization conversion metasurfaces (PCMs) as the parasitic patches to the surface of the radiating patch. Meanwhile, the array formed by the proposed antenna is arranged in a checkerboard form, which makes it have a lower radar cross section (RCS) in the X- and Ku- bands. Even with PCMs loaded, the antenna element maintains a small size of 0.58 λ0 × 0.58 λ0, which ensures the proposed array can achieve the ± 45° beam scanning, making it suitable for the phased array. For verification, we propose a low-sidelobe array composed of the proposed antenna elements, which exhibits a low profile, high FB ratio, and broadband RCS reduction through simulation and measurement.

Flexible and transparent broadband microwave metasurface absorber based on multipolar interference engineering.

Electromagnetic multipoles enable rich electromagnetic interactions in a metasurface and offer another degree of freedom to control electromagnetic responses. In this work, we design and experimentally demonstrate an optically transparent, flexible and broadband microwave metasurface absorber based on multipolar interference engineering. Different from previous works, the designed metasurface simultaneously supports fundamental electric dipole and high-order electric quadrupole mode, whose interference satisfies the back-scattering suppression condition based on the generalized Kerker effect and thus high absorption. The measurement results indicate that the fabricated metasurface exhibits a high average absorption of 89% in the microwave band from 4 GHz to 18 GHz, together with a good optical transparency. Our study offers an alternative approach for designing broadband microwave metasurface absorber, which is potentially applicable in electromagnetic shielding, radar stealth and energy harvesting.

A Retrospective Cohort Study Comparing Traditional Breast Conservation With Oncoplastic Surgery in Breast Cancer Patients After Neoadjuvant Chemotherapy.

BACKGROUND: To better understand the difference between traditional breast-conserving surgery (BCS) and oncoplastic surgery (OPS), we conducted a retrospective cohort study involving breast cancer patients who received neoadjuvant chemotherapy (NAC) and then underwent breast conservation at the Fudan University Shanghai Cancer Center. METHODS: A retrospective chart review was conducted. All breast cancer patients who received NAC and then underwent traditional BCS or OPS at the Fudan University Shanghai Cancer Center from January 1, 2008, to December 31, 2019, were included. RESULTS: Three hundred ninety-nine breast cancer patients received NAC and underwent traditional BCS, and 99 patients underwent OPS. The average age of the patients in the OPS group was younger than that in the BCS group (43 vs 48 years, P = 0.017). The size of the tumor assessed by ultrasonography at baseline in the OPS group was larger than that in the BCS group (31.3 vs 28.1 mm, P = 0.013). The same trend was observed in the clinical T stage and overall staging assessments before the administration of NAC in these 2 groups. Oncoplastic techniques were more frequently applied when tumors were located in areas with relatively few glands, such as the upper inner quadrant. There were no significant differences in the margins and distributions of pathological types and molecular subtypes between these 2 groups. The rates of pathological complete response were similar in the traditional BCS and OPS groups. CONCLUSIONS: Unlike traditional BCS, in breast cancer patients after NAC, the adoption of oncoplastic techniques makes breast conservation feasible, even in patients with large tumors, late stages, and unfavorable tumor locations.