1.The SMAD-Pathway Mediates HMGB1-Induced Proliferation and Metastatic Progression in Cutaneous Squamous Cell Carcinoma Cells
De-De LIAN ; Xue Mei LI ; Yu-Xi JIA ; Ming-Wei ZHOU ; Xiang-Ru CHEN ; Yang-Yang TIAN ; Min LI ; Ming-Hui SUN ; Ye ZHAO ; Hong-Jun LI ; Qing-Ling ZHANG
Annals of Dermatology 2026;38(1):51-58
Background:
High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context.
Objective:
This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC).
Methods:
We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration.
Results:
Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT.
Conclusion
These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.
2.Diagnostic Value of Transrectal Contrast-Enhanced Ultrasound for Rectal Cancer With Intestinal Stenosis.
Qin FANG ; Qin-Xue LIU ; Min-Ying ZHONG ; Wei-Jun HUANG ; Yi-de QIU ; Guo-Liang JIAN
Acta Academiae Medicinae Sinicae 2025;47(5):738-743
Objective To evaluate the diagnostic value of transrectal contrast-enhanced ultrasound (CEUS) for rectal cancer with intestinal stenosis caused by tumors. Methods Forty-nine patients with rectal cancer underwent transrectal CEUS and magnetic resonance imaging (MRI) before surgery.Intraoperative tumor localization and postoperative pathological results were taken as the gold standard for diagnosis.The differences in T stage,localization,and tumor length of rectal cancer were compared between the two methods. Results The total accuracy rates of transrectal CEUS and MRI in diagnosing T stage were 75.5% (36/49) and 67.3% (33/49),which had no significant difference (χ2=0.8,P=0.371).The total accuracy rates of transrectal CEUS and MRI in judging tumor localization were 79.5% (39/49) and 77.5% (38/49),which had no significant difference (χ2=0.061,P=0.806).The measurement results of tumor length in pathological examination had no significant difference from the transrectal CEUS results (t=1.42,P=0.162) but a significant difference from the MRI results (t=3.38,P=0.001).Furthermore,transrectal CEUS detected 8 (16.3%) cases of colonic polyps among the 49 patients,while MRI did not detect colon lesions. Conclusions Transrectal CEUS has good consistency with MRI in T staging and localization judgement of rectal cancer with intestinal stenosis,and this method can more accurately evaluate the tumor length and simultaneously evaluate whether there is a lesion in the entire colon at the proximal end of stenosis.It can be used as a supplementary examination before rectal cancer treatment in clinical practice.
Humans
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Rectal Neoplasms/complications*
;
Male
;
Middle Aged
;
Female
;
Aged
;
Contrast Media
;
Ultrasonography
;
Adult
;
Magnetic Resonance Imaging
;
Constriction, Pathologic/diagnostic imaging*
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Aged, 80 and over
;
Intestinal Obstruction/etiology*
3.Advances in Applications of Machine Learning for Colorimetric Analysis
Yu-Han YAN ; Quan-Feng WANG ; Yu-Tong LAI ; De-Min YANG ; Chang XIA
Chinese Journal of Analytical Chemistry 2025;53(11):1797-1807
Colorimetric analysis is a detection and quantification method based on observable color changes in response to analytes,which offers significant advantages including visually detectable signals,straightforward operation,rapid response,and low cost.Consequently,it plays a crucial role in a variety of fields.With increasingly diverse and complex application,colorimetric analysis requires continuous improvement in sensitivity,adaptability to diverse detection environments,and complex data handling capabilities.In recent years,the development of artificial intelligence technology,particularly within its core domain of machine learning(ML),has led to significant advancements in colorimetric analysis.The ML-assisted colorimetric analysis enables high-throughput and high-sensitivity detection,alongside automated analysis,thereby providing novel strategies to overcome the inherent limitations.This review categorized machine learning techniques and summarized their application in colorimetric analysis,introducing two fundamental categories of supervised learning,and unsupervised learning based on the division of core learning paradigms.The research progress of ML-assisted colorimetric analysis in the fields of environmental monitoring,biochemical detection,and food safety were summarized.Finally,the current challenges facing by this research area were analyzed and the research prospect of ML-assisted colorimetric analysis was outlined.
4.Mechanism of Banxia-Xiexin decoction activating Hippo/YAP signaling pathway to alleviate chronic atrophic gastritis
Jia-min HU ; Yu-jie SUN ; De-bin HUANG
Chinese Pharmacological Bulletin 2025;41(8):1578-1583
Aim To clarify the protective effect of Banxia-Xiexin decoction(BD)on chronic atrophic gastritis(CAG).Methods After establishing a CAG model,BD was used for 4 weeks.The pathological changes in the gastric mucosa were observed through HE staining,while serum biomarkers were detected u-sing ELISA.The expression of key factors in the Hip-po/YAP signaling pathway was examined by RT-qPCR and Western blot.Finally,the expression of YAP and p-YAP proteins was detected by immunefluorescence.Results After BD intervention,the thickness of the gastric mucosa layer,intestinal metaplasia,and inflam-mation in CAG rats showed significant dose-dependent improvement.BD could reduce the expression of IL-6,IL-1β,and TNF-α in the serum of CAG rats,increase the expression of IL-10,and elevate PGR and G-17 lev-els.Following BD intervention,YAP1 was largely phosphorylated and inactivated,with significant increa-ses in p-YAP/YAP protein expression levels and fluo-rescence intensity.Additionally,the protein and mRNA expression levels of MST1 and LATS1 were elevated,indicating the activation of the Hippo/YAP signaling pathway.Conclusions BD exerts a significant phar-macological effect in the treatment of CAG,and its mechanism may be related to the upregulation of MST1-LATS1 protein expression,leading to the inacti-vation of YAP through phosphorylation.
5.Exploring urban versus rural disparities in atrial fibrillation: prevalence and management trends among elderly Chinese in a screening study.
Wei ZHANG ; Yi CHEN ; Lei-Xiao HU ; Jia-Hui XIA ; Xiao-Fei YE ; Wen-Yuan-Yue WANG ; Xin-Yu WANG ; Quan-Yong XIANG ; Qin TAN ; Xiao-Long WANG ; Xiao-Min YANG ; De-Chao ZHAO ; Xin CHEN ; Yan LI ; Ji-Guang WANG ; FOR THE IMPRESSION INVESTIGATORS AND COORDINATORS
Journal of Geriatric Cardiology 2025;22(2):246-254
BACKGROUND:
Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.
METHODS:
Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics.
RESULTS:
The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05).
CONCLUSIONS
In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.
6.Exploring Mechanism of Electroacupuncture in Modulating Neuroinflammation Based on Intestinal Flora and Its Metabolites.
Hai-Min YE ; Zhuo-Yan LI ; Peng ZHANG ; Zhen KANG ; De-Sheng ZHOU
Chinese journal of integrative medicine 2025;31(2):183-192
Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.
Humans
;
Gastrointestinal Microbiome
;
Electroacupuncture
;
Neuroinflammatory Diseases/metabolism*
;
Animals
7.Recanalization Outcomes and Procedural Complications in Patients With Acute Ischemic Stroke and COVID-19 Receiving Endovascular Treatment
João Pedro MARTO ; Davide STRAMBO ; George NTAIOS ; Thanh N NGUYEN ; Pawel WRONA ; Simon ESCALARD ; Simona MARCHESELLI ; Ossama Yassin MANSOUR ; Blanca FUENTES ; Malgorzata DOROBEK ; Marta NOWAKOWSKA-KOTAS ; Elena Oana TERECOASA ; Jonathan M. COUTINHO ; Mariana CARVALHO-DIAS ; Patricia CALLEJA ; João SARGENTO-FREITAS ; Ana PAIVA-NUNES ; Martin ŠRÁMEK ; Priyank KHANDELWAL ; Torcato MEIRA ; Mohamad ABDALKADER ; Pascal JABBOUR ; Martin KOVÁŘ ; Oscar AYO-MARTIN ; Patrik MICHEL ; Roman HERZIG ; Anna CZŁONKOWKSA ; Jelle DEMEESTERE ; Raul G. NOGUEIRA ; Alexander SALERNO ; Susanne WEGENER ; Philipp BAUMGARTNER ; Carlo W. CEREDA ; Giovanni BIANCO ; Morin BEYELER ; Marcel ARNOLD ; Emmanuel CARRERA ; Paolo MACHI ; Valerian ALTERSBERGER ; Leo BONATI ; Henrik GENSICKE ; Manuel BOLOGNESE ; Nils PETERS ; Stephan WETZEL ; Marta MAGRIÇO ; João NUNO RAMOS ; Rita MACHADO ; Carolina MAIA ; Egídio MACHADO ; Patrícia FERREIRA ; Teresa PINHO-E-MELO ; André PAULA ; Manuel Alberto CORREIA ; Pedro CASTRO ; Elsa AZEVEDO ; Luís ALBUQUERQUE ; José NUNO-ALVES ; Joana FERREIRA-PINTO ; Torcato MEIRA ; Liliana PEREIRA ; Miguel RODRIGUES ; André ARAÚJO ; Marta RODRIGUES ; Mariana ROCHA ; Ângelo PEREIRA-FONSECA ; Luís RIBEIRO ; Ricardo VARELA ; Sofia MALHEIRO ; Manuel CAPPELLARI ; Cecilia ZIVELONGHI ; Giulia SAJEVA ; Andrea ZINI ; Gentile MAURO ; Forlivesi STEFANO ; Ludovica MIGLIACCIO ; Maria SESSA ; Sara La GIOIA ; Alessandro PEZZINI ; Davide SANGALLI ; Marialuisa ZEDDE ; Rosario PASCARELLA ; Carlo FERRARESE ; Simone BERETTA ; Susanna DIAMANTI ; Ghil SCHWARZ ; Giovanni FRISULLO ; Pierre SENERS ; Candice SABBEN ; Michel PIOTIN ; Benjamin MAIER ; Guillaume CHARBONNIER ; Fabrice VUILLIER ; Loic LEGRIS ; Pauline CUISENIER ; Francesca R. VODRET ; Gaultier MARNAT ; Jean-Sebastien LIEGEY ; Igor SIBON ; Fabian FLOTTMANN ; Gabriel BROOCKS ; Nils-Ole GLOYER ; Ferdinand O. BOHMANN ; Jan Hendrik SCHAEFER ; Christian H. NOLTE ; Heinrich AUDEBERT ; Eberhard SIEBERT ; Marek SYKORA ; Wilfried LANG ; Julia FERRARI ; Lukas MAYER-SUESS ; Michael KNOFLACH ; Elke-Ruth GIZEWSKI ; Jeffrey STOLP ; Lotte J. STOLZE ; Paul J. NEDERKOORN ; Ido VAN-DEN-WIJNGAARD ; Joke DE MERIS ; Robin LEMMEN ; Sylvie DE RAEDT ; Fenne VANDERVORST ; Matthieu Pierre RUTGERS ; Antoine GUILMOT ; Anne DUSART ; Flavio BELLANTE ; Fernando OSTOS ; Guillermo GONZALEZ-ORTEGA ; Paloma MARTÍN-JIMÉNEZ ; Sebastian GARCÍA-MADRONA ; Antonio CRUZ-CULEBRAS ; Rocio VERA ; Maria-Consuelo MATUTE ; María ALONSO-DE-LECIÑANA ; Ricardo RIGUAL ; Exuperio DÍEZ-TEJEDOR ; Soledad PÉREZ-SÁNCHEZ ; Joan MONTANER ; Fernando DÍAZ-OTERO ; Natalia PEREZ-DE-LA-OSSA ; Belén FLORES-PINA ; Lucia MUÑOZ-NARBONA ; Angel CHAMORRO ; Alejandro RODRÍGUEZ-VÁZQUEZ ; Arturo RENÚ ; Francisco HERNANDEZ-FERNANDEZ ; Tomas SEGURA ; Herbert TEJADA-MEZA ; Daniel SAGARRA-MUR ; Marta SERRANO-PONZ ; Thant HLAING ; Isaiah SEE ; Robert SIMISTER ; David J. WERRING ; Espen Saxhaug KRISTOFFERSEN ; Annika NORDANSTIG ; Katarina JOOD ; Alexandros RENTZOS ; Libor ŠIMU˚NE ; Dagmar KRAJÍČKOVÁ ; Antonín KRAJINA ; Robert MIKULÍK ; Martina CVIKOVÁ ; Jan VINKLÁREK ; David ŠKOLOUDÍK ; Martin ROUBEC ; Eva HURTIKOVA ; Rostislav HRUBÝ ; Svatopluk OSTRY ; Ondrej SKODA ; Marek PERNICKA ; Lubomír KOČÍ ; Zuzana EICHLOVÁ ; Martin JÍRA ; Michal PANSKÝ ; Pavel MENCL ; Hana PALOUŠKOVÁ ; Aleš TOMEK ; Petr JANSKÝ ; Anna OLŠEROVÁ ; Roman HAVLÍČEK ; Petr MALÝ ; Lukáš TRAKAL ; Jan FIKSA ; Matěj SLOVÁK ; Michał KARLIŃSK ; Maciej NOWAK ; Halina SIENKIEWICZ-JAROSZ ; Anna BOCHYNSKA ; Tomasz HOMA ; Katarzyna SAWCZYNSKA ; Agnieszka SLOWIK ; Ewa WLODARCZYK ; Marcin WIĄCEK ; Izabella TOMASZEWSKA-LAMPART ; Bartosz SIECZKOWSKI ; Halina BARTOSIK-PSUJEK ; Marta BILIK ; Anna BANDZAREWICZ ; Justyna ZIELIŃSKA-TUREK ; Krystian OBARA ; Paweł URBANOWSKI ; Sławomir BUDREWICZ ; Maciej GUZIŃSKI ; Milena ŚWITOŃSKA ; Iwona RUTKOWSKA ; Paulina SOBIESZAK-SKURA ; Beata ŁABUZ-ROSZAK ; Aleksander DĘBIEC ; Jacek STASZEWSKI ; Adam STĘPIEŃ ; Jacek ZWIERNIK ; Grzegorz WASILEWSKI ; Cristina TIU ; Razvan-Alexandru RADU ; Anca NEGRILA ; Bogdan DOROBAT ; Cristina PANEA ; Vlad TIU ; Simona PETRESCU ; Atilla ÖZCAN-ÖZDEMIR ; Mostafa MAHMOUD ; Hussam EL-SAMAHY ; Hazem ABDELKHALEK ; Jasem AL-HASHEL ; Ismail IBRAHIM ISMAIL ; Athari SALMEEN ; Abdoreza GHOREISHI ; Sergiu SABETAY ; Hana GROSS ; Piers KLEIN ; Kareem EL NAAMANI ; Stavropoula TJOUMAKARIS ; Rawad ABBAS ; Ghada-A MOHAMED ; Alex CHEBL ; Jiangyong MIN ; Majesta HOVINGH ; Jenney-P TSAI ; Muhib-A KHAN ; Krishna NALLEBALLE ; Sanjeeva ONTEDDU ; Hesham-E MASOUD ; Mina MICHAEL ; Navreet KAUR ; Laith MAALI ; Michael ABRAHAM ; Ivo BACH ; Melody ONG ; Denis BABICI ; Ayaz-M. KHAWAJA ; Maryam HAKEMI ; Kumar RAJAMANI ; Vanessa CANO-NIGENDA ; Antonio ARAUZ ; Pablo AMAYA ; Natalia LLANOS ; Akemi ARANGO ; Miguel A. VENCES ; José-Domingo BARRIENTOS ; Rayllene CAETANO ; Rodrigo TARGA ; Sergio SCOLLO ; Patrick YALUNG ; Shashank NAGENDRA ; Abhijit GAIKWAD ; Kwon-Duk SEO ;
Journal of Stroke 2025;27(1):128-132
8.Application progress of micro-CT and finite element analysis techniques in scaphoid bone research
Yuan LYU ; De-zhou ZHANG ; Hai-long QIAN ; Si-min WANG ; Chao-qun WANG ; Kun LI ; Jie CHEN ; Xue BAI ; Hai-long ZHAO ; Shao-jie ZHANG ; Yuan MA ; Zhi-jun LI ; Jun SHI ; Xing WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(2):168-173
The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.
9.Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.
Kuanyu XIA ; Lang MIN ; Wenqing XIE ; Guang YANG ; Dong Keon YON ; Seung Won LEE ; Ai KOYANAGI ; Louis JACOB ; Lee SMITH ; Jae Il SHIN ; Masoud RAHMATI ; Wenfeng XIAO ; Yusheng LI
Chinese Medical Journal 2025;138(13):1568-1577
BACKGROUND:
The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.
METHODS:
PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.
RESULTS:
Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.
CONCLUSIONS
In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans
;
Arthroplasty, Replacement, Knee/methods*
;
Osteoarthritis, Knee/surgery*
;
Randomized Controlled Trials as Topic
;
Treatment Outcome
10.Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2- advanced breast cancer: Final results of the randomized phase III MONARCH plus trial.
Xichun HU ; Qingyuan ZHANG ; Tao SUN ; Yongmei YIN ; Huiping LI ; Min YAN ; Zhongsheng TONG ; Man LI ; Yue'e TENG ; Christina Pimentel OPPERMANN ; Govind Babu KANAKASETTY ; Ma Coccia PORTUGAL ; Liu YANG ; Wanli ZHANG ; Zefei JIANG
Chinese Medical Journal 2025;138(12):1477-1486
BACKGROUND:
In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis.
METHODS:
In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL).
RESULTS:
In cohort A (abemaciclib: n = 207; placebo: n = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n = 104; placebo: n = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo.
CONCLUSIONS:
Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT02763566).
Humans
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Female
;
Fulvestrant/therapeutic use*
;
Breast Neoplasms/metabolism*
;
Aminopyridines/therapeutic use*
;
Benzimidazoles/therapeutic use*
;
Middle Aged
;
Aromatase Inhibitors/therapeutic use*
;
Aged
;
Receptor, ErbB-2/metabolism*
;
Adult
;
Letrozole/therapeutic use*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Anastrozole/therapeutic use*

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