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The deposition of amyloid-β (Aβ) peptides in senile plaques is one of pathological hallmarks of Alzheimer's disease (AD). Mitochondrial dysfunction is an early event of cell apoptosis. Increasing evidence indicates that Aβ induces neuronal apoptosis through mitochondrial dysfunction. Curcumin, an anti-oxidative component of turmeric (Curcuma longa), has shown anti-tumor, anti-inflammatory, and anti-oxidative properties. In this study, we investigated the protective effects of curcumin against mitochondrial dysfunction induced by Aβ. Based on the assay results of mitochondrial metabolic markers, we found that curcumin protects human neuroblastoma SH-SY5Y cells against the Aβ-induced damage of mitochondrial energy metabolism. Curcumin inhibits Aβ-induced mitochondrial depolarization of membrane potential (Δψm) and suppresses mitochondrial apoptosis-related proteins including cytochrome c, caspase-3, and Bax, which are activated by Aβ. Aβ-induced disturbances of redox state are linked to mitochondrial dysfunction. Curcumin normalizes cellular antioxidant enzymes (including SOD and catalase) in both protein expression and activity and decreases oxidative stress level in Aβ-treated cells. Both total GSK-3β expression and phospho-Ser9 GSK-3β (pSer9-GSK-3β) are down-regulated in the cells pre-treated with curcumin. This study demonstrates curcumin-mediated neuroprotection against Aβ-induced mitochondrial metabolic deficiency and abnormal alteration of oxidative stress. Inhibition of GSK-3β is involved in the protection of curcumin against Aβ-induced mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Facile synthesis of high-efficiency and stable bifunctional electrocatalyst is essential for producing clean hydrogen in energy storage systems. Herein, low Rh-doped flower-like Ni 3 S 2 /Co 3 S 4 heterostructures were facilely prepared on porous nickel foam (labeled Rh-Ni 3 S 2 /Co 3 S 4 /NF) by a hydrothermal method. The correlation of the precursors types with the morphological structures and catalytic properties were rigorously investigated for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the control groups. The low Rh doping within the catalyst played important role in boosting the catalytic characteristics. The resulting catalyst showed the smaller overpotentials of 197 and 78 mV to drive a current density of 10 mA cm -2 for the OER and HER in alkaline electrolyte, respectively. And the potential only required 1.71 V to drive a current density of 100 mA cm -2 in a water splitting device. It reflects excellent overall water splitting of the home-made Rh-Ni 3 S 2 /Co 3 S 4 /NF. This strategy shed some constructive light for preparing transition metal sulfide-based electrocatalysts in water splitting devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the last decades, 4-nitrophenol is regarded as one of highly toxic organic pollutants in industrial wastewater, which attracts great concern to earth sustainability. Herein, atomically dispersed ternary FeCoNb active sites were incorporated into nitrogen-doped honeycomb-like mesoporous carbon (termed FeCoNb/NHC) by a two-step pyrolysis strategy, whose morphology, structure and size were characterized by a set of techniques. Further, the catalytic activity and reusability of the as-prepared FeCoNb/NHC were rigorously examined by using 4-NP catalytic hydrogenation as a proof-of-concept model. The influence of the secondary pyrolysis temperature on the catalytic performance was investigated, combined by illuminating the catalytic mechanism. The resultant catalyst exhibited significantly enhanced catalytic features with a normalized rate constant (k app ) of 1.2 × 10 4 min -1 g -1 and superior stability, surpassing the home-made catalysts in the control groups and earlier research. This study provides some constructive insights for preparation of high-efficiency and cost-effectiveness single-atom nanocatalysts in organic pollutants environmental remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Printer source prediction is an important task when examining questioned documents. While some research has provided methods to predict the source printer of documents, with the advent of compatible consumables, printer prediction could become more complex and difficult. Predicting the source printer after replacing cartridges and identifying the source of printer cartridges are unresolved issues that are rarely addressed in current research. Herein, we introduce a novel technique to predict the manufacturer, model, and cartridges of laser printers (i.e., compatible, and original cartridges) used to produce a given document. Document samples produced using eight laser printers and 247 cartridges were collected to establish a dataset. Common manufacturers included HP, Canon, Lenovo, and Epson. After obtaining white-light images and three-dimensional profile images of printed characters, a morphological analysis was conducted by questioned document examiners (QDEs) using microscopy. Microscopic image features across a series of images were also extracted and analyzed using algorithms. Then, six high-dimensional reduction algorithms were used to obtain between- and within-printer variations as well as between- and within-cartridge variations. Finally, we conducted principal component analysis (PCA) and discriminant analysis. For 40 % of the samples, mixed discrimination analysis (MDA) and fixed discrimination analysis (FDA) were employed to predict the manufacturer, model and cartridge of laser printers used to produce the questioned printed document; the remaining 60 % samples comprised the training dataset. In the prediction of manufacturer, model and cartridge, our method achieved mean accuracies of 95.5 %, 97.5 %, and 90.2 %, respectively. Hence, this technique could reasonably aid in predicting the manufacturer, model, and cartridge of a laser printer, even if different cartridges are loaded into printers., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ 2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] ( P <0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance ( P =0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95% CI : 4.3-5.7) and 4.0 (95% CI : 1.6-6.4) months, respectively, with no statistical significance ( P =0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95% CI : 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95% CI : 1.8-2.2) months] ( P <0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95% CI : 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95% CI : 0.6-3.4) months] ( P =0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

A novel technique is introduced to predict the printer model used to produce a given document. Samples containing only a few letters printed under varying conditions (i.e., different printing modes, letter types, fonts) were collected to establish a dataset of 41 inkjet printer models from common manufacturers, such as HP, Canon, and Epson. Morphological features were analyzed by extraction of image features using several algorithms in a series of microscopic images and a Wilcoxon test was used to measure the significance of variations between printed samples. Significant differences between various printing conditions might post potential challenge to questioned document examination. Discriminant analysis and the k-nearest neighbor (KNN) algorithm were also employed for source printer prediction under varying printing condition on 30% images with the rest images as training dataset. The results of a validation experiment demonstrated that while quadratic discriminant analysis (QDA) achieved an accuracy of 96.3%, a combination of KNN and QDA reached 98.6%. As such, this technique could aid in the forensic examination of printed documents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.)

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1β, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Imbalance between excitation and inhibition is an important cause of epilepsy. Salt-inducible kinase 1 (SIK1) gene mutation can cause epilepsy. In this study, we first found that the expression of SIK3 is increased after epilepsy. Furthermore, the role of SIK3 in epilepsy was explored. In cultured hippocampal neurons, we used Pterosin B, a selective SIK3 inhibitor that can inhibit epileptiform discharges induced by the convulsant drug cyclothiazide (a positive allosteric modulator of AMPA receptors, CTZ). Knockdown of SIK3 inhibited epileptiform discharges and increased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). In mice, knockdown of SIK3 reduced epilepsy susceptibility in a pentylenetetrazole (a GABA A receptor antagonist, PTZ) acute kindling experiment and increased the expression of GABA A receptor α1. In conclusion, our results suggest that blockade or knockdown of SIK3 can inhibit epileptiform discharges and that SIK3 has the potential to be a novel target for epilepsy treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Design: Retrospective cohort study., Objective: To investigate the effect of HRVA on the intrapedicular accuracy of C2PS placement through the freehand method in patients with BI and analyse the possible risk factors for C2PS malpositioning., Method: A total of 91 consecutive patients with BI who received 174 unilateral C2PS placements through the freehand method were retrospectively included. The unilateral pedicles were assigned to the HRVA and non-HRVA groups. The primary outcome was the intrapedicular accuracy of C2PS placement in accordance with the Gertzbein-Robbins scale. Moreover, the risk factors that possibly affected intrapedicular accuracy were assessed., Results: The rate of intrapedicular accuracy in C2PS placement in patients with BI was 23.6%. Results showed that the non-HRVA group had remarkably higher rates of optimal and clinically acceptable C2PS placement than the HRVA group. Nevertheless, the HRVA group exhibited similar results for grade B classification as the non-HRVA group. Moreover, in the HRVA and non-HRVA groups, the most common direction of screw deviations was the lateral direction. Furthermore, the multivariate analyses showed that the obliquity of the lateral atlantoaxial joint in the sagittal plane ≥15°, and that in the coronal plane ≥ 20°, isthmus height < 4.3 mm, and distance from the skin to the spinous process ≥ 2.8 cm independently contributed to a high rate of screw malpositioning in BI patients., Conclusion: The presence of HRVA in BI patients contributed to the high rate of malpositioning in C2PS placement via the freehand method. However, the rates of intrapedicular accuracy in patients with BI with and without HRVA were considerably low., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

With the advent of the precision cancer therapy era, neoadjuvant therapy has become the standard therapy for certain types of breast cancer. Neoadjuvant therapy is a fundamental treatment plan implemented at the time of disease diagnosis, and its efficacy can guide the formulation of subsequent adjuvant therapy strategies. Building on the efficacy of neoadjuvant therapy and medication regimens, in conjunction with evidence-based medicine and healthcare policy, developing adjuvant therapy strategies for breast cancer following neoadjuvant therapy has the benefit of providing more precise treatment options for patients.

Introduction: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI., Methods: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR +/+ ) and PXR-knockout (PXR -/- ) mice. The N2a H 2 O 2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process., Results: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro., Conclusion: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Endocrine therapy is the primary systemic therapy for hormone receptor-positive breast cancer, which runs through the whole process of treatment for early and metastatic breast cancer. The development of new endocrine agents and targeted drugs such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors has improved outcome of patients with hormone receptor-positive breast cancer and changed the treatment landscape. The update of clinical research data provides more treatment options, calling for treatment optimization. Experts had a deep discussion around the hot topics on endocrine therapy of breast cancer, and formulated the'Expert consensus on endocrine therapy of breast cancer (2023 edition)'.This consensus is based on research data worldwide and clinical practice experience, with the aims of standardizing clinical diagnosis and optimizing treatment in neoadjuvant, adjuvant and metastatic setting of hormone receptor-positive breast cancer.

In the past decade, generated data of large-scale clinical research of endocrine therapy and the update of guidelines have changed clinical practice of breast cancer treatment. However, there are unresolved issues on endocrine therapy. Based on new evidences and clinical experience, we expounded our points on neoadjuvant endocrine therapy, CDK4/6 inhibitoradjuvant therapy, concepts of endocrine sensitivity and endocrine resistance, first-line treatment for metastatic breast cancer, treatment options after progression on CDK4/6 inhibitor and treatment ofvisceral crisis.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies., Competing Interests: Disclosure MLTAT declares consulting fees and honoraria from MSD, Roche, Novartis, Eli Lilly and AstraZeneca. HKA declares consulting fees from Daiichi Sankyo, Amgen, Yuhan and Novartis, and honoraria from Roche, BMS, MSD, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Menarini, Eisai, Pfizer, Boryung Pharmaceutical Company, Celtrion, Pharmobio Korea Inc. and Yuhan. GC has served as consultant or advisor for Roche, Eli Lilly and BMS; served on a speaker’s bureau for Roche, Pfizer and Eli Lilly; received travel funding from Pfizer and Roche; and received honoraria from Roche, Pfizer, Eli Lilly, Novartis, AstraZeneca and SeaGen, all outside the submitted work. THF declares honoraria from AstraZeneca Oncology Indonesia, Takeda Indonesia, Eisai Indonesia, Roche Oncology Indonesia, J & J Indonesia and Zueling Pharma Indonesia and role as head of division of Area Development for West Java, Indonesia for the Indonesian Society of Hematology and Medical Oncology. AG declares honoraria for advisory boards from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Pfizer and Roche; honoraria for lectures from Eisai and Eli Lilly and honoraria for expert testimony from Gentili. SG declares honoraria from Lupin, Roche, Novartis, Eli Lilly, Eisai, Cipla, CADILA, Intas and AstraZeneca; honoraria for being on committees of the Indian Council of Medical Research (Government of India), Council of Scientific and Industrial Research (Government of India), Department of Biotechnology (Government of India), India Alliance and institutional; honoraria from Novartis and AstraZeneca for participation in steering committees; leadership roles include President of Indian Society of Medical and Paediatric Oncology and General Secretary of Women’s Cancer Initiative - Tata Memorial Hospital, both roles unpaid. NH reports honoraria for lectures, advisory boards and/or personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz and SeaGen, and minority ownership interest in the West German Study Group. RAH declares honoraria from Roche, Novartis, MSD, Pfizer and Mylan, and support for attending meetings from Roche, MSD and Kalbe Pharma. SAI declares an institutional grant from AstraZeneca, Boryung Pharm, Daewoong Pharm, Eisai, Roche and Pfizer, and honoraria from AstraZeneca, Novartis, MSD, Roche, Pfizer; advisory role for AstraZeneca, Bertis, Daiichi Sankyo, Eisai, Hanmi, Lilly, MSD, Novartis, Roche and Pfizer. JHK declares an institutional grant from Ono Pharma Ltd., and honoraria from Novartis, MSD, Roche Pharma, Roche diagnostics, Pfizer, AstraZeneca, Eisai, Lilly, and Sanofi; fees for participation in data monitoring or advisory boards from Bixink, Eisai, Yuhan, Novartis, Daiichi Sankyo, Pfizer, Roche Pharma and Everest Medicines; institutional gifts from Eisai and Ono Pharma Ltd. SBK declares institutional funding from Novartis, Sanofi-Aventis and Dongkook Pharm Co.; consulting fees from Novartis, AstraZeneca, Lilly, DaeHwa Pharmaceutical Co Ltd., ISU Abxis, Beigene, OBI Pharma and Daiichi Sankyo; honoraria from Novartis, Pfizer, Lilly, OBI Pharma and Legochem Bioscience; participation on data safety monitoring or advisory boards for Novartis, AstraZeneca, MSD, Lilly and Daiichi Sankyo, and purchased stock in Genopeaks and Neogene TC. KHL declares honoraria from Pfizer, Novartis and Eli Lilly. SCL declares grants from Pfizer, Eisai, Taiho, ACT Genomics, MSD, Adagene and Epizyme; honoraria from Pfizer, Novartis, AstraZeneca, ACT Genomics, Eli Lilly, MSD and Roche and participation in data monitoring or advisory boards for Pfizer, Novartis, Eisai, Sanofi, Daiichi Sankyo, MSD and Roche. MYM declares institutional grants from MSD, Astella, Pfizer, Novartis, AstraZeneca, ARCUS, Amgen and honoraria from MSD, Amgen, Pfizer, Roche, Novartis, Zuelling Pharma, Specialised therapeutics, Eisai, GSK, Mundi Pharma, Eli Lilly and AstraZeneca. YN declares institutional grants from the Ministry of Health, Labour and Welfare, Abbvie, Ono, Daiichi Sankyo, Taiho, Pfizer, Boehringer Ingelheim, Eli Lilly, Eisai, AstraZeneca, Chugai, Bayer and honoraria from AstraZeneca, Eisai, Ono, Gardant, Takeda, Eli Lilly, Novartis, Pfizer, Chugai, Fuji Film Toyama Chemistry, Taiho, Mundi, Bristol, Shionogi. NP declares honoraria from AstraZeneca, Eisai, Roche, Eli Lilly, Novartis, Pfizer and MSD. YHP declares grants from AstraZeneca, Pfizer, Novartis, Roche and Gencurix, consulting fees from AstraZeneca, Pfizer, Novartis, Roche, Eisai, Daiichi Sankyo, MSD and Lilly, honoraria from Pfizer, MSD, Novartis and Roche, and participation on data monitoring boards and advisory boards for Roche, Eisai, Daiichi Sankyo, AstraZeneca, MSD and Novartis. SP declares fees for consultancy/advisory roles from Abbvie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Bio Invent, Biocartis, Blueprint Medicines, Boehringer Ingelheim, BMS, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-star, Foundation Medicine, Genzyme, Gilhead, GSK, Illumina, Incyte, IQIVIA, iTHeos, Janssen, Medscape, MSD, Merck Serono, Mirati, Novartis, Novocure, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, SeaGen, Takeda, Vaccibody, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Fishawack, Illumina, Imedex, Medscape, Mirati MSD, Novartis, OncologyEducation, PER, Pfizer, PRIME, RMEI, Roche/Genentech, RTP, Sanofi, Takeda and steering committee and trial chair roles as follows: AstraZeneca, coordinating PI, institutional, no financial interest, MERMAID-1; AstraZeneca, steering committee member, institutional, no financial interest, MERMAID-2, POSEIDON, MYSTIC; Beigene, steering committee member, institutional, no financial interest, BGB-A317-A1217-301/AdvanTIG-301; BMS, steering committee member, institutional, no financial interest, clinical trial steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451; BMS, steering committee member, institutional, no financial interest, RELATIVITY 095; GSK, trial chair, institutional, no financial interest, clinical trial chair ZEAL-1; iTeos, steering committee member, institutional, no financial interest, Phase 2 Inupadenant with chemo; Mirati, steering committee member, institutional, no financial interest, clinical trial steering committee SAPPHIRE; MSD, steering committee member, institutional, no financial interest, clinical trial steering committee PEARLS, MK-7684A; Pharma Mar, steering committee member, institutional, no financial interest, LAGOON; Phosplatin Therapeutics, steering committee member, institutional, no financial interest, phase 1/2 trials; Roche/Genentech, trial chair, institutional, no financial interest, clinical trial chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte. Also role as ESMO president, ETOP/EORTC/SAKK PI, involved in academic trials, ETOP/IBCSG partners officer. Council member and scientific chair, SAKK, vice-President Lung Group, SAMO, Vice President. BKS declares honoraria from Novartis and Eli Lilly. MS declares honoraria from AstraZeneca, MSD, Accord Health and Novartis, support for attending meetings from the Malaysia Urology Association and roles as an ex-committee member of the Malaysian Oncological Society and chairman of the Annual Scientific congress of the Malaysian Oncological Society. KT declares grants from Pfizer, Daiichi Sankyo, Eli Lilly, AstraZeneca, Eisai; honoraria from Daiichi Sankyo, Eli Lilly, Chugai, MSD; and data monitoring or advisory board fees from Daiichi Sankyo. SSW declares a grant from Pfizer and honoraria from Pfizer, Roche, AstraZeneca, Novartis, Daiichi Sankyo, Eli Lilly, MSD and Henrui. TY declares institutional grants from Amgen, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Genomedia, MSD, Ono, Pfizer, Sanofi, Sysmex and Taiho, and honoraria Bayer, Chugai, Merck biopharma, MSD and Ono. All other authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since trastuzumab was listed and approved for breast cancer in 2002, China has entered a new epoch of targeted therapy. Over the past 20 years, anti-human epidermal growth factor receptor 2 (HER2) targeted therapy for breast cancer in China has experienced the era of single-target, tyrosine kinase inhibitors, double-target and anti-HER2 plus antibody-drug conjugate. Advancement in the anti-HER2 targeted therapy is continuously changing the treatment mode of patients with HER2 positive status and even HER2 low expression, significantly improved their prognosis. In the past 20 years, Chinese scholars have participated in international clinical researches, completed a series of registration studies of imported drugs, developed new drugs with proprietary intellectual property rights, enriched the evidence of clinical research on HER2-targeted therapy, and formed a treatment system with both international standards and Chinese characteristics. In particular, the formulation of the Chinese Society of Clinical Oncology Breast Cancer Guidelines and the Chinese expert consensus on anti-HER2 targeted treatment in breast cancer are the concentrated embodiments of Chinese wisdom.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC)., Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites., Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07)., Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer QZ declared a shared parent affiliation with the author TH to the handling editor at the time of review., (Copyright © 2023 Fan, Zhang, Yang, Yi, Ouyang, Yan, Wang, Hu, Jiang, Huang, Tong, Wang, Yin, Li, Yang, Yang, Teng, Sun, Cai, Li, Ouyang, He, Liu, Yang, Wang, Xu and Qiao.)

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P <0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.

Objective: Patients with basilar invagination (BI) had high incidences of vertebral variations and high-riding vertebral artery (HRVA) that might restrict the use of pedicle or pars screw and increase the use of translaminar screw on axis. Here, we conducted a radiographic study to investigate the feasibility of translaminar screws and the bone quality of C2 laminae in patients with BI, which were compared with those without BI as control to provide guidelines for safe placement., Methods: In this study, a total of 410 patients (205 consecutive patients with BI and 205 matched patients without BI) and 820 unilateral laminae of the axis were included at a 1:1 ratio. Comparisons with regard to insertion parameters (laminar length, thickness, angle, and height) for C2 translaminar screw placement and Hounsfield unit (HU) values for the assessment of the appropriate bone mineral density of C2 laminae between BI and control groups were performed. Besides, the subgroup analyses based on the Goel A and B classification of BI, HRVA, atlas occipitalization, and C2/3 assimilation were also carried out. Furthermore, the factors that might affect the insertion parameters and HU values were explored through multiple linear regression analyses., Results: The BI group showed a significantly smaller laminar length, thickness, height, and HU value than the control group, whereas no significant difference was observed regarding the laminar angle. By contrast, the control group showed significantly higher rates of acceptability for unilateral and bilateral translaminar screw fixations than the BI group. Subgroup analyses showed that the classification of Goel A and B, HRVA, atlas occipitalization, and C2/3 assimilation affected the insertion parameters except the HU values. Multiple linear regression indicated that the laminar length was significantly associated with the male gender (B = 0.190, p < 0.001), diagnoses of HRVA (B = -0.109, p < 0.001), Goel A (B = -0.167, p < 0.001), and C2/3 assimilation (B = -0.079, p = 0.029); the laminar thickness was significantly associated with the male gender (B = 0.353, p < 0.001), diagnoses of HRVA (B = -0.430, p < 0.001), Goel B (B = -0.249, p = 0.026), and distance from the top of odontoid to the Chamberlain line (B = -0.025, p = 0.003); laminar HU values were significantly associated with age (B = -2.517, p < 0.001), Goel A (B = -44.205, p < 0.001), Goel B (B = -25.704, p = 0.014), and laminar thickness (B = -11.706, p = 0.001)., Conclusion: Patients with BI had narrower and smaller laminae with lower HU values and lower unilateral and bilateral acceptability for translaminar screws than patients without BI. Preoperative 3-dimensional computed tomography (CT) and CT angiography were needed for BI patients.

We report here the development of clickable and highly near-infrared (NIR) fluorescent lanthanide (Ln) complexes for bioorthogonal labeling of biomolecules. These azide- or alkyne-functionalized Ln complexes are hydrophilic and fluorogenic, exhibiting a strong increase of NIR fluorescence upon conjugation with biomolecules. Metabolic labeling of biomolecules with azide or alkyne, followed by click labeling with the Ln complexes, enables NIR fluorescence (NIRF) imaging of DNA, RNA, proteins, and glycans in cells. Furthermore, multicolor imaging is performed by combining click-labeling with the Ln complexes and immunostaining. In addition, the Ln complexes is compatible with click-expansion microscopy (click-ExM), which enables high-resolution NIRF imaging of cellular glycoproteins. Finally, the Ln complexes can be used for time-of-flight secondary-ion mass spectrometry (ToF-SIMS) imaging, thus achieving the first example of dual-modal imaging combining NIRF and SIMS microscopies., (© 2022 Wiley-VCH GmbH.)

The intestinal mucosa is a highly compartmentalized structure that forms a direct barrier between the host intestine and the environment, and its dysfunction could result in a serious disease. As T cells, which are important components of the mucosal immune system, interact with gut microbiota and maintain intestinal homeostasis, they may be involved in the process of intestinal barrier dysfunction. P2X7 receptor (P2X7R), a member of the P2X receptors family, mediates the effects of extracellular adenosine triphosphate and is expressed by most innate or adaptive immune cells, including T cells. Current evidence has demonstrated that P2X7R is involved in inflammation and mediates the survival and differentiation of T lymphocytes, indicating its potential role in the regulation of T cell function. In this review, we summarize the available research about the regulatory role and mechanism of P2X7R on the intestinal mucosa-derived T cells in the setting of intestinal barrier dysfunction., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers., Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis., Results: A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HR age 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HR bone metastasis =0.74, 95% CI: 0.59-0.93; HR lung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HR bone metastasis =0.69, 95% CI: 0.48-0.98; HR lung metastasis =0.48, 95% CI: 0.31-0.74)., Conclusions: Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-302/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: C2 pedicle screw placement in patients with basilar invagination (BI) is fraught with risks because of a high incidence of anatomical variations and high-riding vertebral artery (HRVA). However, no study can be found in the literature that attempted to identify the ideal entry point and trajectory through the C2 pedicle in BI patients with HRVA., Purpose: To investigate the parameters of ideal entry point and trajectory for C2 pedicle screw placement in BI patients with HRVA and compare them with those in BI patients without HRVA and patients without BI as control. These parameters would serve as a guide to pedicle screw placement., Study Design: A retrospective comparative study., Patient Sample: A total of 396 patients (198 consecutive BI patients and 198 matched patients without BI as control) and 792 unilateral pedicles from April 2017 to October 2021 at two medical centers were included., Outcome Measures: The insertion parameters of mediolateral angle, surface distance, cephalad angle, and vertical distance from the superior border of the lamina were the primary outcome measures for the reference of C2 pedicle screw placement. Furthermore, factors that affect the primary insertion parameters were assessed via multiple linear regression analyses., Method: According to the diagnosis of BI and HRVA, the unilateral pedicles were assigned into HRVA of BI, non-HRVA of BI, HRVA of control, and non-HRVA of control groups. Subgroup analyses based on Goel types A and B were also performed. Moreover, vertebral artery (VA) anomalies that might result in potentially serious complications were identified and systematically compared., Results: The measurements of insertion parameters in BI patients with HRVA indicated a mean mediolateral angle of 27.42°, a mean cephalad angle of 43.02°, a mean surface distance of 9.74 mm, and a mean vertical distance from the superior border of the lamina of 3.85 mm. Compared with that in BI patients without HRVA, the measurements suggested that the entry point in BI patients with HRVA should be shifted upward by 0.38 mm and the trajectory should be angled cephalad by 6.05° and medially by 4.78°. In the control group, changes in the insertion parameters between HRVA and non-HRVA showed a similar trend to the BI group. Multiple linear regression showed that mediolateral angle was significantly associated with the male gender (B=-0.930, p=.017) and the diagnoses of HRVA (B=6.964, p<.001), Goel type A (B=-1.656, p=.003), and Goel type B (B=0.981, p=.030). Moreover, cephalad angle was significantly associated with the length of lateral mass (B=-0.319, p=.001) and the diagnoses of HRVA (B=3.254, p<.001) and Goel type A (B=6.924, p<.001). The VA anomalies were significantly higher in the BI group than in the control group., Conclusions: The insertion parameters of the ideal entry point and trajectory for C2 screw placement in BI patients with HRVA were remarkably different from those of non-HRVA of BI, HRVA of control, and non-HRVA of control cohorts. Preoperative 3D computed tomography (CT) and CT angiography are highly recommended in such patients to improve intraoperative safety and reduce postoperative complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To analyze the acupoint selection rules of acupuncture for pseudobulbar palsy dysphagia using data mining technology., Methods: The literature of acupuncture for pseudobulbar palsy dysphagia published from January 1, 1990 to May 1, 2021 was retrieved from CNKI, SinoMed, Wanfang, VIP, and PubMed databases. Acupuncture prescription database was established. The frequency of acupoint selection was analyzed by Microsoft Excel 2016; Apriori algorithm was used to analyze the association rules and draw the high-frequency acupoint co-occurrence network diagram; SPSS21.0 was used to perform clustering analysis., Results: A total of 87 literature was included, involving 89 acupuncture prescriptions and 71 acupoints. Fengchi (GB 20) was the most frequently-used acupoint; the commonly-selected meridians were gallbladder meridian, conception vessel, governor vessel and stomach meridian; the acupoints located at the neck were the most frequently-used acupoints; the crossing points were commonly selected among the special acupoints. The most commonly-used acupoint combination was Jinjin (EX-HN 12) plus Yuye (EX-HN 13)., Conclusion: The modern acupuncture for pseudobulbar palsy dysphagia usually selects local acupoints, especially the neck acupoints such as Fengchi (GB 20) and Lianquan (CV 23). The acupoints in the front and back are concurrently selected with needles towards the disease location.

With the development of new strategies like target therapy and immunotherapy, early breast cancer treatment has become more standardized, and the interval of disease free survival has been extended. Although guidelines and expert consensus have provided supports for clinical decision making, there are still some controversial issues in clinical practice, attributing to different treatment concepts, product indications and accessibility. These controversial issues would eventually affect the treatment of early breast cancer. This year in 2021, the approval of new indications of drugs like abemaciclib and the popularity of dual anti-human epidermal growth factor receptor 2 targeted drugs have promoted the change of treatment modalities for different types of early breast cancer. To this end, ten hot topics of early breast cancer are summarized according to their different molecular typing and treatment stages for discussion.

In recent years, many researches have explored the diagnostic value of Raman spectroscopy in multiple types of tumors. However, as an emerging clinical examination method, the diagnostic performance of Raman spectroscopy in lung cancer remains unclear. Relevant diagnostic studies published before 1 June 2020 were retrieved from the Cochrane Library, PubMed, EMBASE, China National Knowledge Internet (CNKI), and WanFang databases. After the literature was screened, two authors extracted the data from eligible studies according to the inclusion and exclusion criteria. Obtained data were pooled and analyzed using Stata 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. Fourteen diagnostic studies were eligible for the pooled analysis which includes 779 patients. Total pooled sensitivity and specificity of Raman spectroscopy in diagnosing lung cancer were 0.92 (95% CI 0.87-0.95) and 0.94 (95% CI 0.88-0.97), respectively. The positive likelihood ratio was 15.2 (95% CI 7.5-30.9), the negative likelihood ratio was 0.09 (95% CI 0.05-0.14), and the area under the curve was 0.97 (95 % CI 0.95-0.98). Subgroup analysis suggested that the sensitivity and specificity of RS when analyzing human tissue, serum, and saliva samples were 0.95 (95% CI 0.88-0.98), 0.97 (95% CI 0.89-0.99), 0.88 (95% CI 0.80-0.93), 0.87 (95% CI 0.78-0.92), 0.91 (95% CI 0.80-0.96), and 0.95 (95% CI 0.73-0.99), respectively. No publication bias or threshold effects were detected in this meta-analysis. This initial meta-analysis indicated that Raman spectroscopy is a highly specific and sensitive diagnostic technology for detecting lung cancer. Further investigations are also needed to focus on real-time detection using Raman spectroscopy under bronchoscopy in vivo. Moreover, large-scale diagnostic studies should be conducted to confirm this conclusion., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data., Methods: Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated., Results: A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy. The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed., Conclusions: Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4273). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Objective: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice., Methods: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database., Results: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected., Conclusion: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yi-Qun Han et al.)

Phosgene may induce acute lung injury (ALI) when a person is exposed to it. Mesenchymal stem cells (MSCs) were affirmed to have therapeutic effects on phosgene-induced ALI. In a previous study, ALI exosomes have been confirmed to promote the proliferation and migration of MSCs. However, the mechanism of this phenomenon is still unclear. MicroRNAs (miRNAs) are essential in the physiological process of cells. In this study, lung-derived exosomes were isolated from phosgene-exposed and normal rats, respectively, through ultracentrifugation and cultured MSCs with these exosomes. We found that rno-miR-34c-3p was downregulated in MSCs cocultured with ALI exosomes. MiR-34c-3p inhibitor promoted the proliferation and migration of MSCs. Moreover, the dual-luciferase reporter assay demonstrated that miR-34c-3p regulated Janus kinase 1 (JAK1) expression. The miR-34c-3p inhibitor also significantly activated the JAK1/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, ALI exosomes decrease the miR-34c-3p expression levels, influencing MSCs via the JAK1/STAT3 signaling pathway., (© 2021 Wiley Periodicals LLC.)

Objective: Since the first publication in 2017, the Chinese society of clinical oncology breast cancer guidelines have been updated in four editions, and nearly 300 000 volumes have been published, which has been widely recognized by scholars at home and abroad. The important updates from pathological diagnosis to therapies in the newest guideline has been updated in accordance with evidence, drug accessibility and expert opinions. Meanwhile, more chapters, like drug adverse reaction management, real-world research, biosimilar drugs, have been added, making a comprehensive guideline in guiding breast cancer standardized diagnosis and treatment.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides and play important roles in a variety of diseases. LncRNAs are involved in many biologic processes including cell differentiation, development, and apoptosis. The intestinal barrier is considered one of the most important protective barriers in humans. Severe damage or dysfunction of the intestinal barrier may be associated with the occurrence and development of many diseases, such as inflammatory bowel disease and ulcerative colitis. LncRNAs have been found to be associated with intestinal barrier function in some studies, which are at an early stage. In this review, we introduce the roles of LncRNAs in the intestinal barrier and investigate the possibility of lncRNAs as a research field in the intestinal barrier.

In this work, an efficient and sensitive magnetic molecularly imprinted polymer with zein and deep eutectic solvents (ZDM-MIPs) was designed and synthesized to exclusively adsorb and detect aspartame (ASP). We used zein, together with deep eutectic solvents (DESs) and Fe 3 O 4 as the cross-linker, functional monomer and support material, respectively. A magnetic glassy carbon electrode (MGCE) modified with ZDM-MIPs was used for selective recognition of ASP. The electrochemical response of the ZDM-MIPs-MGCE for quantification of ASP was evaluated with a portable electrochemical detection station with differential pulse voltammetry and cyclic voltammetry. The responses of ZDM-MIPs-MGCE signified a good linear relationship with ASP concentrations in the range of 0.1-50 μg mL -1 . The sensor systems showed good accuracy and precision, with recovery percentages between 84% and 107%. These results suggested that the obtained ZDM-MIPs exhibited good adsorption performance for ASP in soft drinks, and this method could be used to determine ASP content in actual food samples., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival., (© 2020 Union for International Cancer Control.)

Triple negative breast cancer (TNBC) is a special type of breast cancer. At present, the major treatment for TNBC is chemotherapy. Neoadjuvant therapy and obtained pathology completed response could bring the TNBC patients better prognosis. The most used TNBC chemotherapy protocols are established on the basis of anthracycline and taxane. Through the thorough knowledge of molecular mechanism of TNBC, neoadjuvant therapy protocols have optimized, including the use of platinum, immune checkpoint inhibitors and poly-ADP-ribose polymerase inhibitors, and assumed positive outcome for TNBC patients.

Paclitaxel (PTX) is a powerful anticancer natural product, with its separation and purification having been widely studied. In this work, new molecular imprinted polymers (MIPs) using deep eutectic solvents (DESs) with different molar ratios were prepared as functional monomers. These were then used as adsorbents in solid phase extraction (SPE) for the separation of PTX from its structural analogs. The polymers were characterized by energy disperive X-rays (EDX), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and fourier transform infrared spectroscopy (FT-IR). The results suggested that the formative regular DES-MIPs had an even pore-size distribution and a large specific surface area. The dynamic adsorption and static adsorption showed that the DES-MIPs had excellent adsorption performance, with a maximum adsorption capacity and optimum adsorption time of 87.08 mg/g and 180 min, respectively. The selective adsorption experiments showed that the material had outstanding selectivity, and the maximum selectivity factor was 6.20. For stability, after six consecutive adsorption and desorption cycles, the DES-MIPs maintained the perfect stability and reusability. Furthermore, the fabricated SPE column was successfully utilized for extracting and eluting PTX. This study provides a reliable protocol for the separation and purification PTX from its structural analogs and the DES-MIPs materials have excellent potential application value in pharmaceutical industry., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are small noncoding RNAs stretching over 18-22 nucleotides and considered to be modifiers of many respiratory diseases. They are highly evolutionary conserved and have been implicated in several biological processes, including cell proliferation, apoptosis, differentiation, among others. Acute lung injury (ALI) is a fatal disease commonly caused by direct or indirect injury factors and has a high mortality rate in intensive care unit. Changes in expression of several types of miRNAs have been reported in patients with ALI. Some miRNAs suppress cellular injury and accelerate the recovery of ALI by targeting specific molecules and decreasing excessive immune response. For this reason, miRNAs are proposed as potential biomarkers for ALI and as therapeutic targets for this disease. This review summarizes current evidence supporting the role of miRNAs in ALI.

Human epidermal growth factor receptor-2 (HER-2) tyrosine kinase inhibitors (TKI) is the targeted drug of HER-2-positive breast cancer. Lapatinib, pyrotinib and neratinib, as ErbB family TKIs, have been approved by National Medical Products Administration and applied in the treatment of HER-2 positive breast cancer in China. The most common adverse effects (AEs) of TKI agents include diarrhea, drug-induced liver injury (DILI), nausea, vomiting, skin toxicity, cardiotoxicity and oral mucositis. The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence and characteristics of AEs of TKI, evaluated the manifestations and severity of AEs, and formulated the consensus of the management of common AEs based on the clinical experiences and updated advances from domestic and abroad studies. This consensus aims to provide the practical strategy for clinicians in the management of ErbB-family TKI-related AEs in China, and eventually enhance the patients' compliance and improve the therapeutic efficacy.

Aim: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa., Methods: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A., Results: In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p  = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm ( p  < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p  < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm ( p  < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B)., Conclusion: The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population. Trial Registration: ClinicalTrials.gov identifier: NCT02763566., Competing Interests: Conflict of interest: RBH, YL and HDC are employees and minor shareholders of Eli Lilly and Company. XHW has received research funding from Eli Lilly and Company. QYZ, TS, YMY, HPL, MY, ZST, CPO, YPL, RC, ML, YC, QCO, XC, NL, XJW, JFF, RH, GBK, MAC-P, ZJ and XCH have no conflicts of interest to declare., (© The Author(s), 2020.)

Increasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.

Cervical cancer (CC) is the second most common malignancy in women worldwide. The mechanism underlying CC development remains unclear. Recently, Circular RNAs (circRNAs)have attracted attention because of its role in tumorigenesis. To investigate circRNAsin CC, RNA sequencing was employed to characterize circRNA expression profile between CC tissues and matched adjacent normal tissues. The expression of hsa&#95;circ&#95;0003204 was examined in CC tissues and cell lines by real-time PCR. Migration assay and invasion assay were used to verify the effect of hsa&#95;circ&#95;0003204 on migration and invasion ability in CC cell lines. Tumor formation assay in nude mice was used to analyze the effect of hsa&#95;circ&#95;0003204 on the tumorigenicity of CC cell lines in vitro. Western blotting analyzes were performed to investigate the role of hsa&#95;circ&#95;0003204 in the regulation of MAPK signaling activation. We found that circRNA hsa&#95;circ&#95;0003204 was significantly upregulated in CC tissues. The function and potential molecular mechanisms of hsa&#95;circ&#95;0003204 were also investigated in vitro and in vivo. Hsa&#95;circ&#95;0003204 knockdown reduced cell growth, migration, and invasion but promoted cells apoptosis. However, the over-expression of hsa&#95;circ&#95;0003204 had the opposite effect. The MAPK pathway was different in hsa&#95;circ&#95;0003204 over-expression or down-expression cells, compared to parental cells. In addition, over-expression of hsa&#95;circ&#95;0003204 significantly increased tumor volume and tumor weight in vivo.Taken together, results indicated hsa&#95;circ&#95;0003204 may serve as a potential therapeutic target for patients with CC.

Objective: To evaluate the clinical efficacy and safety of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer. Methods: Patients were randomized 2∶1 to test group and control group. Patients in test group received Cipterbin (4 mg/kg loading dose and 2 mg/kg maintenance dose each week, IV) combined with vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV). Patients in control group received vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV).The primary end point was progression free survival (PFS). Results: A total of 315 patients were enrolled from Jan 2009 to Jan 2013 (212 in test group and 103 in control group). The median PFS of test group was significantly longer than that of control group, 39.1 weeks vs 14.0 weeks ( HR =0.24; 95 %CI , 0.16-0.36; P< 0.000 1). The objective response rate (ORR) and disease control rate (DCR) in test group were significantly higher than those in control group, ORR was 46.7% vs 18.45% ( P< 0.000 1) and DCR was 79.72% vs 45.63% ( P< 0.000 1). The incidence of neutropenia, leucopenia and erythrocytopenia were higher in both groups, but there was no significant difference between two groups.The most common adverse events associated with Cipterbin were infusion reactions. Left ventricular ejection fraction reduced to less than 50% in 5 patients, which were recovered. No serious cardiotoxicity. Conclusion: The recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine has significant efficacy and good safety. It is the optimized therapy regime for patients with taxane-pretreated HER2 positive metastatic breast cancer, which provides more targeted therapy opportunities for HER2 positive breast cancer patients in China.

Objective: To explore the related risk factors of hemorrhage in human brain cerebral arteriovenous malformations (AVM) and the relationship between endothelial progenitor cells (EPCs) content and stromal cell-derived factor-1 (SDF-1) in different ages., Methods: A retrospective analysis was conducted on 130 patients with cerebral AVM who underwent surgical treatment from May 2012 to October 2018. Univariate and multivariate logistic analysis was used to investigate the related risk factors of cerebral AVM hemorrhage. Forty paraffin specimens of human brain AVM were harvested from 24 cases of cerebral hemorrhage patients and 16 cases of non-cerebral hemorrhage patients Paraffin samples of cerebral cortex from 8 patients with epilepsy during the same period were selected as control. Positive expression of CD34 and vascular endothelial growth factor receptor 2 (KDR2) in brain tissue samples of both groups were used to identify EPCs. Immunofluorescence double staining was used for KDR2 and CD34 positive localization to determine EPCs localization, and SDF-1 expression detection was performed., Results: The size of brain AVM<3 cm, deep brain AVM and single venous drainage are independent risk factors for cerebral AVM hemorrhage. Immunohistochemical results showed that CD34 and KDR2 were expressed in cerebral AVM group, but not in the control group. Double immunofluorescence staining showed that EPCs mainly existed at the edge of vascular wall, while SDF-1 could co-stain with alpha-smooth muscle actin (α-SMA) positive cells and CD31 positive cells. SDF-1 expression in brain AVM tissue was higher than that in control group. There were significant differences in the number of EPCs among the patients of different ages ( P <0.05). There was no significant difference in EPCs between cerebral hemorrhage group and non-hemorrhage group ( P >0.05)., Conclusion: Brain AVM (<3 cm), single venous drainage and deep brain AVM are independent risk factors for cerebral AVM hemorrhage. In human brain AVM, EPC appears high level but decrease with age, which may play a role in vascular remodeling in AVM., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Cadmium-free quantum dots (QDs) are attracting considerable research attention because of their low toxicity. However, the bandgap of most cadmium-free QDs avoids the pure-blue region, which leads to difficulty in realizing pure-blue quantum-dot light-emitting diodes (QLEDs). In this work, we successfully tuned the emission wavelength of ZnSe/ZnS quantum dots from the violet region (∼420 nm) to the pure-blue region (450-460 nm) by doping Te into the ZnSe core. The ZnSe:0.03Te/ZnSeS/ZnS QD sample with emission at 450 nm and a quantum yield of 30% was the most balanced formula. To overcome the energy gap between the hole-transfer layer and QD layers, a specific hole-transfer layer was developed for normal-structure QLEDs. A QLED with such a structure with ZnSe:0.03Te/ZnSeS/ZnS QDs achieved the pure-blue light emission at 455 nm, a low turn-on voltage of 4.4 V, and an external quantum efficiency of 0.33%. Overall, our cadmium-free QLED achieved pure-blue emission, revealing the potential of ZnSe-based pure-blue QLEDs for future displays.