Major influencing factors identification and probabilistic health risk assessment of soil potentially toxic elements pollution in coal and metal mines across China: A systematic review.

Deposition of potentially toxic elements (PTEs) in soils due to different types of mining activities has been an increasingly important concern worldwide. Quantitative differences of soil PTEs contamination and related health risk among typical mines remain unclear. Herein, data from 110 coal mines and 168 metal mines across China were analyzed based on 265 published literatures to evaluate pollution characteristics, spatial distribution, and probabilistic health risks of soil PTEs. The results showed that PTE levels in soil from both mine types significantly exceeded background values. The geoaccumulation index (Igeo) revealed metal-mine soil pollution levels exceeded those of coal mines, with average Igeo values for Cd, Hg, As, Pb, Cu, and Zn being 3.02-15.60 times higher. Spearman correlation and redundancy analysis identified natural and anthropogenic factors affecting soil PTE contamination in both mine types. Mining activities posed a significant carcinogenic risk, with metal-mine soils showing a total carcinogenic risk an order of magnitude higher than in coal-mine soils. This study provides policymakers a quantitative foundation for developing differentiated strategies for sustainable remediation and risk-based management of PTEs in typical mining soils.

Method for Estimating Road Impulse Ahead of Vehicles in Urban Environment with Microelectromechanical System Three-Dimensional Sensor.

Most automated vehicles (AVs) are equipped with abundant sensors, which enable AVs to improve ride comfort by sensing road elevation, such as speed bumps. This paper proposes a method for estimating the road impulse features ahead of vehicles in urban environments with microelectromechanical system (MEMS) light detection and ranging (LiDAR). The proposed method deploys a real-time estimation of the vehicle pose to solve the problem of sparse sampling of the LiDAR. Considering the LiDAR error model, the proposed method builds the grid height measurement model by maximum likelihood estimation. Moreover, it incorporates height measurements with the LiDAR error model by the Kalman filter and introduces motion uncertainty to form an elevation weight method by confidence eclipse. In addition, a gate strategy based on the Mahalanobis distance is integrated to handle the sharp changes in elevation. The proposed method is tested in the urban environment. The results demonstrate the effectiveness of our method.

Total Synthesis of (+)-Shearilicine.

Herein we report the first total synthesis of the indole diterpenoid natural product shearilicine by an 11-step sequence via a generalizable precursor to the highly oxidized subclass of indole diterpenoids. A native chiral auxiliary strategy was employed to access the target molecule in an enantiospecific fashion. The formation of the key carbazole substructure was achieved through a mild intramolecular Heck cyclization, wherein a computational study revealed noncovalent substrate-ligand and ligand-ligand interactions that promoted migratory insertion.

Copper-Catalyzed Hydroamination: Enantioselective Addition of Pyrazoles to Cyclopropenes.

Chiral N-cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, and enantiocontrol. The observed N2:N1 regioselectivity favors the more hindered nitrogen of the pyrazole. Experimental and DFT studies support a unique mechanism that features a five-centered aminocupration.

PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827-0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.

Safety and efficacy associated with single-fraction high-dose-rate brachytherapy in localized prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: Although single-fraction high-dose-rate brachytherapy (SFHDR) for localized prostate cancer has been tried in clinical trials, relevant medical evidence is currently lacking. It is necessary to systematically analyze the safety and efficacy of SFHDR. METHODS: Comprehensive and systematic searches for eligible studies were performed in PubMed, Embase, and the Cochrane Library databases. The primary endpoints included safety and efficacy, represented by toxic effects and biochemical recurrence-free survival (bRFS), respectively. The proportion rates were used as the effect measure for each study and were presented with corresponding 95% confidence intervals (CI) and related 95% prediction interval (PI). Restricted maximum-likelihood estimator (REML) and the Hartung-Knapp method were used in the meta-analysis. RESULTS: Twenty-five studies met the inclusion criteria for quantitative analysis, including 1440 patients. The median age of patients was 66.9 years old (62-73 years old) and the median follow-up was 47.5 months (12-75 months). The estimates of cumulative occurrence for severe gastrointestinal (GI) and genitourinary (GU) toxic effects were 0.1% (95% CI 0-0.2%) and 0.4% (95% CI 0-1.2%), and for grade 2 toxic effects were 1.6% (95% CI 0.1-4.7%) and 17.1% (95% CI 5.4-33.5%), respectively. The estimate of 3­year bRFS was 87.5% (95% CI 84.4-90.3%) and 71.0% (95% CI 63.0-78.3%) for 5­year bRFS. The pooled bRFS rates for low-risk patients were 99.0% (95% CI 85.2-100.0%) at 3 years and 80.9% (95% CI 75.4-85.9%) at 5 years, and the risk group was found to be statistically correlated with bRFS (3-year bRFS, P < 0.01; 5­year bRFS, P = 0.04). CONCLUSION: SFHDR is associated with favorable tolerability and suboptimal clinical benefit in patients with localized prostate cancer. Ongoing and planned high-quality prospective studies are necessary to verify its safety and efficacy.

Mn-N-C catalysts derived from metal triazole framework with hierarchical porosity for efficient oxygen reduction.

Manganese and nitrogen co-doped porous carbon (Mn-N-C) are proposed as one of the most up-and-coming non-precious metal electrocatalysts to substitute Pt-based in the oxygen reduction reaction (ORR). Herein, we chose metal triazole frameworks as carbon substrate with hierarchical porosity for trapping and anchoring Mn-containing gaseous species by a mild one-step pyrolysis method. The optimized Mn-N-C electrocatalyst with a large metal content of 1.71 wt% and a volume ratio of 0.86 mesopores pore delivers a superior ORR activity with a half-wave potential (E1/2) of 0.92 V in 0.1 M KOH and 0.78 V in 0.1 M HClO4. Moreover, the modified Mn-N-C catalyst showed superior potential cyclic stability. TheE1/2remained unchanged in 0.1 M KOH and only lost 6 mV in 0.1 M HClO4after 5000 cycles. When applied as the cathode catalyst in Zn-air battery, it exhibited a maximum peak power density of 176 mW cm-2, demonstrating great potential as a usable ORR catalyst in practical devices.

Nitrogen-doped hollow mesoporous carbon spheres for efficient oxygen reduction.

Extensive investigations have been devoted to nitrogen-doped carbon materials as catalysts for the oxygen reduction reaction (ORR) in various conversion technologies. In this study, we introduce nitrogen-doped carbon materials with hollow spherical structures. These materials demonstrate significant potential in ORR activity within alkaline media, showing a half-wave potential of 0.87 V versus the reversible hydrogen electrode (RHE). Nitrogen-doped hollow carbon spheres (N-CHS) exhibit unique characteristics such as a thin carbon shell layer, hollow structure, large surface area, and distinct pore features. These features collectively create an optimal environment for facilitating the diffusion of reactants, thereby enhancing the exposure of active sites and improving catalytic performance. Building upon the promising qualities of N-CHS as a catalyst support, we employ heme chloride (1 wt%) as the source of iron for Fe doping. Through the carbonization process, Fe-N active sites are effectively formed, displaying a half-wave potential of 0.9 V versus RHE. Notably, when implemented as a cathode catalyst in zinc-air batteries, this catalyst exhibits an impressive power density of 162.6 mW cm-2.

Risk Control Values and Remediation Goals for Benzo[a]pyrene in Contaminated Sites: Sectoral Characteristics, Temporal Trends, and Empirical Implications.

Benzo[a]pyrene (BaP) is a highly carcinogenic pollutant of global concern. There is a need for a comprehensive assessment of regulation decisions for BaP-contaminated site management. Herein, we present a quantitative evaluation of remediation decisions from 206 contaminated sites throughout China between 2011 and 2021 using the cumulative distribution function (CDF) and related statistical methodologies. Generally, remediation decisions seek to establish remediation goals (RGs) based on the risk control values (RCVs). Cumulative frequency distributions, followed non-normal S-curve, emerged multiple nonrandom clusters. These clusters are consistent with regulatory guidance values (RGVs), of national and local soil levels in China. Additionally, priority interventions for contaminated sites were determined by prioritizing RCVs and identifying differences across industrial sectors. Notably, we found that RCVs and RGs became more relaxed over time, effectively reducing conservation and unsustainable social and economic impacts. The joint probability curve was applied to model decision values, which afforded a generic empirically important RG of 0.57 mg/kg. Overall, these findings will help decision-makers and governments develop appropriate remediation strategies for BaP as a ubiquitous priority pollutant.

Commutability evaluation of candidate reference materials and ERM-DA470k/IFCC for immunoglobulin M using two international approaches.

BACKGROUND: This study aimed to assess the commutability of frozen pooled human serum (PHS), high concentration of Immunoglobulin M (IgM) pure diluted materials (HPDM), commercialized pure materials (CPM), and dilutions of ERM-DA470k/IFCC in IgM detection using the CLSI and IFCC approaches, to support standardization or harmonization of IgM measurement. METHODS: Twenty-four serum samples, relevant reference materials (PHS, HPDM, CPM), and different ERM-DA470k/IFCC dilutions were analyzed in triplicate using six routine methods. The commutability of the relevant reference materials was carried out following CLSI EP30-A and IFCC bias analysis. RESULTS: According to the CLSI approach, low, medium, and high concentrations of PHS, HPDM, and CPM were commutable on 10, 13, 15, 13, and 8 of 15 assay combinations, respectively. Using the IFCC approach, low, medium, and high concentrations of PHS, HPDM, and CPM were commutable on 10, 11, 9, 15, and 10 of 15 assay combinations, respectively. The ERM-DA470k/IFCC dilutions with D-PBS and RPMI-1640 Medium were commutable on 13 of 15 assay combinations according to CLSI and were commutable on all 15 assay combinations using IFCC approach. CONCLUSIONS: High concentration of PHS were commutable on all six detection systems using the CLSI approach. Low and medium concentration of PHS showed unsatisfied commutability. HPDM, not CPM have good commutability, has the potential to become reference materials. ERM-DA470k/IFCC diluted with different medium showed different commutability.

Pyrazine-linked Iron-coordinated Tetrapyrrole Conjugated Organic Polymer Catalyst with Spatially Proximate Donor-Acceptor Pairs for Oxygen Reduction in Fuel Cells.

Nitrogen-coordinated iron (Fe-N4 ) materials represent the most promising non-noble electrocatalysts for the cathodic oxygen reduction reaction (ORR) of fuel cells. However, molecular-level structure design of Fe-N4 electrocatalyst remains a great challenge. In this study, we develop a novel Fe-N4 conjugated organic polymer (COP) electrocatalyst, which allows for precise design of the Fe-N4 structure, leading to unprecedented ORR performance. At the molecular level, we have successfully organized spatially proximate iron-pyrrole/pyrazine (FePr/Pz) pairs into fully conjugated polymer networks, which in turn endows FePr sites with firmly covalent-bonded matrix, strong d-π electron coupling and highly dense distribution. The resulting pyrazine-linked iron-coordinated tetrapyrrole (Pz-FeTPr) COP electrocatalyst exhibits superior performance compared to most ORR electrocatalysts, with a half-wave potential of 0.933 V and negligible activity decay after 40,000 cycles. When used as the cathode electrocatalyst in a hydroxide exchange membrane fuel cell, the Pz-FeTPr COP achieves a peak power density of ≈210 mW cm-2 . We anticipate the COP based Fe-N4 catalyst design could be an effective strategy to develop high-performance catalyst for facilitating the progress of fuel cells.

SNCA inhibits epithelial-mesenchymal transition and correlates to favorable prognosis of breast cancer.

Alpha-synuclein (SNCA) is a pathological hallmark of Parkinson's disease, known to be involved in cancer occurrence and development; however, its specific effects in breast cancer remain unknown. Data from 150 patients with breast cancer were retrieved from tissue microarray and analyzed for SNCA protein level using immunohistochemistry. Functional enrichment analysis was performed to investigate the potential role of SNCA in breast cancer. SNCA-mediated inhibition of epithelial-mesenchymal transition (EMT) was confirmed with western blotting. The effects of SNCA on invasion and migration were evaluated using transwell and wound-healing experiments. Furthermore, the potential influence of SNCA expression level on drug sensitivity and tumor infiltration by immune cells was analyzed using the public databases. SNCA is lowly expressed in breast cancer tissues. Besides, in vitro and in vivo experiments, SNCA overexpression blocked EMT and metastasis, and the knockdown of SNCA resulted in the opposite effect. A mouse model of metastasis verified the restriction of metastatic ability in vivo. Further analysis revealed that SNCA enhances sensitivity to commonly used anti-breast tumor drugs and immune cell infiltration. SNCA blocks EMT and metastasis in breast cancer and its expression levels could be useful in predicting the chemosensitivity and evaluating the immune microenvironment in breast cancer.

Surface Anion Promotes Pt Electrocatalysts with High CO Tolerance in Fuel-Cell Performance.

Platinum reaches considerable activity and stability as an electrocatalyst but is not always capable of maintaining such performance under CO poisoning, particularly in CO residual fuels for practical proton-exchange membrane fuel cells (PEMFCs). In this work, we report that surface anions including a series of nonmetal elements on Pt nanoparticles result in outstanding CO tolerance for electrocatalysts in fuel cells. In particular, phosphorus surface-anion-modified Pt (denoted as P-Pt) possesses more than 10-fold enhancement of CO tolerance (only 8.4% decay) than commercial Pt/C, which can serve as a robust electrocatalyst both in CO poisoning half cells and full cells. Moreover, the general mechanism and principle were proposed, stating that surface anions should be selected preferentially to offer electron feedback to downshift the d-band center for the Pt surface, successfully weakening CO adsorption and leading to high-tolerance capability. We anticipate that surface anions on a Pt surface can bring robust electrocatalysts for practical PEMFCs and offer novel insights for high-performance Pt-based electrocatalysts.

Association of peripheral basophils with tumor M2 macrophage infiltration and outcomes of the anti-PD-1 inhibitor plus chemotherapy combination in advanced gastric cancer.

BACKGROUND: Although the anti-programmed death-1 (PD-1) inhibitor plus chemotherapy combination has been approved as the standard first-line treatment for advanced gastric cancer, a proportion of patients do not significantly benefit from this therapy. Who would respond poorly to this treatment and the underlying mechanisms of treatment failure are far from clear. METHODS: We retrospectively analyzed the associations between the peripheral basophils at baseline and clinical outcomes in 63 advanced gastric cancer patients treated with anti-PD-1 plus chemotherapy and 54 patients treated with chemotherapy alone. Immunohistochemistry and immunofluorescence staining in gastric cancer samples were utilized to investigate the basophil-related immunophenotype. RESULTS: The optimal cutoff of basophil count to distinguish responders to anti-PD-1 plus chemotherapy from non-responders was 20.0/µL. Compared with the low basophil group (≤ 20.0/µL, n = 40), the high basophil group (> 20.0/µL, n = 23) had a significantly lower objective response rate (ORR 17.4% vs. 67.5%, p = 0.0001), worse progression-free survival (median PFS 4.0 vs. 15.0 months, p = 0.0003), and worse overall survival (median OS not reached, p = 0.027). Multivariate analyses identified a basophil count of > 20.0/µL as an independent risk factor for a worse ORR (OR 0.040, 95% CI 0.007-0.241, p = 0.0004), worse PFS (HR 3.720, 95% CI 1.823-7.594, p = 0.0003) and worse OS (HR 3.427, 95% CI 1.698-6.917, p = 0.001). In contrast, there was no significant association between peripheral basophil counts and tumor response or survival in the chemotherapy-alone group (p > 0.05). In primary gastric cancer samples, we observed a correlation between higher peripheral basophil counts and the accumulation of tumor-infiltrating basophils (r = 0.6833, p = 0.005). Tumor-infiltrating basophils were found to be spatially proximate to M2 macrophages within TME and positively correlated with tumor M2 macrophage infiltration (r = 0.7234, p = 0.0023). The peripheral basophil counts also had a significant positive correlation with tumor-infiltrating M2 macrophage counts (r = 0.6584, p = 0.003). Further validation in tumor samples treated with the neoadjuvant anti-PD-1 inhibitor plus chemotherapy combination suggests that the peripheral basophils, tumor infiltration of basophils, and M2 macrophages were significantly more abundant in non-responders than in responders (p = 0.0333, p = 0.0007, and p = 0.0066, respectively). CONCLUSIONS: The peripheral basophil count was observed to be a potential biomarker of anti-PD-1 efficacy for advanced gastric cancer. Moreover, basophils may induce an immune-evasive tumor microenvironment by increasing M2 macrophage infiltration, which could be a potential immunotherapeutic target for advanced gastric cancer.

Photoswitches with different numbers of azo chromophores for molecular solar thermal storage.

We investigate three azo-chromophore-containing photoswitches (1, 2 and 3) for molecular solar thermal storage (MOST) based on reversible Z-E isomerization. 1, 2 and 3 are photoswitchable compounds that contain one, two and three azo chromophores, respectively. In solution, 1, 2 and 3 were charged via UV-light-induced E-to-Z isomerization. Among these three compounds, 2 exhibited an energy density as high as 272 ± 1.8 J g-1, which showed the best energy storage performance. This result originated from the low molecular weight, a high degree of photoisomerization, and moderate steric hindrance of 2, which demonstrated the advantages of the meta-bisazobenzene structure for MOST. In addition, we studied the performances of these photoswitches in the solvent-free state. Only 1 showed photoinduced reversible solid-to-liquid transitions, which enabled the charging of 1 in a solvent-free state. The stored energy density for 1 in a solvent-free state was 237 ± 1.5 J g-1. By contrast, 2 and 3 could not be charged in the solvent-free state due to the lack of solid-state photoisomerization. Our findings provide a better understanding of the structure-performance relationship for azobenzenebased MOST and pave the way for the development of high-density solar thermal fuels.

Predicting incidence of hepatitis E using machine learning in Jiangsu Province, China.

Hepatitis E is an increasingly serious worldwide public health problem that has attracted extensive attention. It is necessary to accurately predict the incidence of hepatitis E to better plan ahead for future medical care. In this study, we developed a Bi-LSTM model that incorporated meteorological factors to predict the prevalence of hepatitis E. The hepatitis E data used in this study are collected from January 2005 to March 2017 by Jiangsu Provincial Center for Disease Control and Prevention. ARIMA, GBDT, SVM, LSTM and Bi-LSTM models are adopted in this study. The data from January 2009 to September 2014 are used as the training set to fit models, and data from October 2014 to March 2017 are used as the testing set to evaluate the predicting accuracy of different models. Selecting models and evaluating the effectiveness of the models are based on mean absolute per cent error (MAPE), root mean square error (RMSE) and mean absolute error (MAE). A total of 44 923 cases of hepatitis E are detected in Jiangsu Province from January 2005 to March 2017. The average monthly incidence rate is 0.35 per 100 000 persons in Jiangsu Province. Incorporating meteorological factors of temperature, water vapour pressure, and rainfall as a combination into the Bi-LSTM Model achieved the state-of-the-art performance in predicting the monthly incidence of hepatitis E, in which RMSE is 0.044, MAPE is 11.88%, and MAE is 0.0377. The Bi-LSTM model with the meteorological factors of temperature, water vapour pressure, and rainfall can fully extract the linear and non-linear information in the hepatitis E incidence data, and has significantly improved the interpretability, learning ability, generalisability and prediction accuracy.

Do spatiotemporal units matter for exploring the microgeographies of epidemics?

From the onset of the COVID-19 pandemic in 2020, studies on the microgeographies of epidemics have surged. However, studies have neglected the significant impact of multiple spatiotemporal units, such as report timestamps and spatial scales. This study examines three cities with localized COVID-19 resurgence after the first wave of the pandemic in mainland China to estimate the differential impact of spatiotemporal unit on exploring the influencing factors of epidemic spread at the microscale. The quantitative analysis results suggest that future spatial epidemiology research should give greater attention to the "symptom onset" timestamp instead of only the "confirmed" data and that "spatial transmission" should not be confused with "spatial sprawling" of epidemics, which can greatly reduce comparability between epidemiology studies. This research also highlights the importance of considering the modifiable areal unit problem (MAUP) and the uncertain geographic context problem (UGCoP) in future studies.

Single-shot wavefront sensing with deep neural networks for free-space optical communications.

Applying deep neural networks in image-based wavefront sensing allows for the non-iterative regression of the aberrated phase in real time. In view of the nonlinear mapping from phase to intensity, it is common to utilize two focal plane images in the manner of phase diversity, while algorithms based on only one focal plane image generally yield less accurate estimations. In this paper, we demonstrate that by exploiting a single image of the pupil plane intensity pattern, it is possible to retrieve the wavefront with high accuracy. In the context of free-space optical communications (FSOC), a compact dataset, in which considerable low-order aberrations exist, is generated to train the EfficientNet which learns to regress the Zernike polynomial coefficients from the intensity frame. The performance of ResNet-50 and Inception-V3 are also tested in the same task, which ended up outperformed by EfficientNet by a large margin. To validate the proposed method, the models are fine-tuned and tested with experimental data collected in an adaptive optics platform.

Flexible Neural Probes with Electrochemical Modified Microelectrodes for Artifact-Free Optogenetic Applications.

With the rapid increase in the use of optogenetics to investigate nervous systems, there is high demand for neural interfaces that can simultaneously perform optical stimulation and electrophysiological recording. However, high-magnitude stimulation artifacts have prevented experiments from being conducted at a desirably high temporal resolution. Here, a flexible polyimide-based neural probe with polyethylene glycol (PEG) packaged optical fiber and Pt-Black/PEDOT-GO (graphene oxide doped poly(3,4-ethylene-dioxythiophene)) modified microelectrodes was developed to reduce the stimulation artifacts that are induced by photoelectrochemical (PEC) and photovoltaic (PV) effects. The advantages of this design include quick and accurate implantation and high-resolution recording capacities. Firstly, electrochemical performance of the modified microelectrodes is significantly improved due to the large specific surface area of the GO layer. Secondly, good mechanical and electrochemical stability of the modified microelectrodes is obtained by using Pt-Black as bonding layer. Lastly, bench noise recordings revealed that PEC noise amplitude of the modified neural probes could be reduced to less than 50 µV and no PV noise was detected when compared to silicon-based neural probes. The results indicate that this device is a promising optogenetic tool for studying local neural circuits.

Neoadjuvant Pyrotinib plus Trastuzumab and Chemotherapy for Stage I-III HER2-Positive Breast Cancer: A Phase II Clinical Trial.

LESSONS LEARNED: This is the first trial to explore the neoadjuvant therapy of pyrotinib in HER2-positive operable and locally advanced breast cancer, in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab. Results primarily showed that pyrotinib in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab was effective and safe in HER2-positive operable and locally advanced breast cancer. A subsequent randomized controlled trial is still warranted to confirm these results. BACKGROUND: The efficacy and safety of neoadjuvant therapy of pyrotinib, a new irreversible tyrosine kinase inhibitor (TKI), was first estimated in patients with HER2-positive breast cancer in this phase II study, in combination with trastuzumab and chemotherapy. METHODS: Between February 19, 2019, and November 20, 2019, 20 female Chinese patients with stage I-III HER2-positive breast cancer were assigned to receive eight cycles of neoadjuvant pyrotinib (P) in combination with four cycles of epirubicin (E) and cyclophosphamide (C) followed by four cycles of docetaxel (T) and trastuzumab (H), once every 3 weeks, referred to as P + EC-TH. RESULTS: A total of 19 patients completed the therapy and final surgery. The total pathological complete response (tpCR) rate was 73.7% (95% confidence interval [CI], 48.8-90.9), and no recurrence or metastasis occurred during the short-term follow-up period. The objective response rate (ORR) was 100% (95% CI, 82.4-100). The most common adverse events (AEs) were diarrhea and leukopenia in 18 of 20 patients (90%), but no grade 5 AEs were reported. CONCLUSION: This study showed that in HER2-positive operable or locally advanced breast cancer, the tpCR rate of P + EC-TH neoadjuvant therapy was about twice as high as that of EC-TH neoadjuvant therapy reported in other trials, with tolerable side effects.