1.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
2.Practice and optimization pathways of the surveillance - response system for schistosomiasis during the elimination stage in China: a One Health perspective
Jiajia WAN ; Jingye SHANG ; Jing XU ; Chen PU ; Nannan WANG ; Rongzhi LI ; Yu ZHANG ; Liang XU ; Xianhong MENG ; Ding LU ; Lin CHEN ; Zisong WU ; Bo ZHONG ; Xiaonong ZHOU ; Yang LIU
Chinese Journal of Schistosomiasis Control 2026;38(4):361-368
This paper systematically analyzes schistosomiasis transmission risks during the elimination stage and reviews the evolution of the schistosomiasis surveillance system in China from a One Health perspective, with a special emphasis on schistosomiasis surveillance and response practices during the elimination stage from a One Health perspective. These practices include precise screening of human schistosomiasis under low-endemicity conditions, systematic monitoring of schistosomiasis in domestic and wild animals, ecological management of Oncomelania snails, and information-coordinated responses. Nevertheless, the current surveillance and response system for schistosomiasis suffers from challenges of insufficient cross-sectoral coordination and complex external environments, which constrain precise schistosomiasis surveillance and response in China. Therefore, it is urgently necessary to integrate coordination mechanisms, empower the surveillance system with technological innovation, improve capacity building, and actively promote diverse social participation in the One Health framework, so as to consolidate current schistosomiasis control achievements and achieve the target for schistosomiasis elimination across China, which may provide a replicable technical model for global zoonoses control.
3.Single-cell transcriptomic insights into endosulfan-induced liver injury:Key pathways and inflammatory responses
Pan HUANG ; Yunmeng BAI ; Chaohua ZHOU ; Xiaoru ZHONG ; Ashok IYASWAMY ; Peng CHEN ; Xu WEI ; Wei ZHANG ; Chuanbin YANG ; Jigang WANG
Liver Research 2025;9(2):144-156
Background and aims:Environmental pollutants,particularly organochlorine insecticides like endosulfan(ENDO),are increasingly linked to liver toxicity and related diseases.Despite its widespread historical use,the mechanisms underlying ENDO-induced liver damage remain poorly understood.This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity.Methods:C57BL/6 mice were exposed to ENDO for two weeks.Single-cell RNA sequencing(scRNA-seq)was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level.Differentially expressed genes(DEGs)across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO.Transcription factor(TF)regulatory network,pseudotime trajectory,and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure.Results:ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells and lymphocytes,triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes.Additionally,ENDO exposure led to the recruitment and activation of myeloid cells,contributing to the inflammatory milieu.An increase in intercellular communication and changes to the hepatic microenvironment,especially the interaction between activated hepatic stellate cells and CD8+T cells were observed,further implicating these processes in ENDO-induced liver damage.Conclusions:This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO.Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution.These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.
4.Efficacy of Shuyao Huoxue Tongluo Decoction Combined with Meridian Acupoint Massage in Treating Patients with Lumbar Disc Herniation of Qi-Stagnation and Blood-Stasis Type and Its Impacts on Serological Indicators
Lin ZHOU ; Yanyuan ZHONG ; Wei YE ; Songhui LAN ; Hang YANG ; Zhihong TAN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(8):1905-1912
Objective To investigate the clinical efficacy of Shuyao Huoxue Tongluo Decoction combined with meridian acupoint massage in treating lumbar disc herniation(LDH)patients with qi-stagnation and blood-stasis syndrome,and to analyze its effects on serological indicators.Methods A total of 120 LDH patients with qi-stagnation and blood-stasis syndrome admitted to Huizhou Hospital of Guangzhou University of Chinese Medicine from December 2023 to December 2024 were enrolled.The patients were randomly divided into control group and study group using a random number table,with 60 cases in each group.The control group received conventional treatment(including lumbar traction and drug therapy)combined with meridian acupoint massage,while the study group received additional Shuyao Huoxue Tongluo Decoction based on the treatment for the control group.Before and after treatment,the scores of traditional Chinese Medicine(TCM)syndrome,Visual Analogue Scale(VAS)scores for pain,Japanese Orthopedic Association(JOA)scores for lumbar function,Oswestry Disability Index(ODI)scores,and serum levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in the two groups were compared.After treatment,the clinical efficacy was evaluated between groups.Results(1)After 20 days of treatment,the total effective rate was 95.00%(57/60)in the study group versus 81.67%(49/60)in the control group(tested by chi-square test,P<0.05),demonstrating significantly superior therapeutic effects in the study group.(2)After treatment,both groups showed significant reduction in TCM syndrome scores(P<0.01),and the study group exhibited markedly decrease compared to the control group(P<0.01).(3)After treatment,the VAS scores for pain in both groups were significantly decreased compared to those before treatment(P<0.01),and the study group exhibited obvious decrease of the scores than the control group(P<0.01).(4)After treatment,JOA scores for lumbar function in both groups were increased(P<0.05),while Oswestry Disability Index(ODI)scores were decreased(P<0.05),compared to those before treatment,and the study group demonstrated more significant improvements in both JOA score elevation and ODI score reduction(P<0.05).(5)For serum inflammatory factors,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels in both groups were significantly reduced(P<0.05)after treatment,and the study group showed more pronounced decrease in both markers(P<0.05).Conclusion Compared with meridian acupoint massage alone,the combined therapy of Shuyao Huoxue Tongluo Decoction and meridian acupoint massage is effective on significantly alleviating clinical symptoms,reducing serum inflammatory factors,and enhancing overall therapeutic outcomes in LDH patients with qi-stagnation and blood-stasis syndrome.
5.Effects of LSS function deficiency on intestinal function in NAFLD model mice
Hongmei Bai ; Zhen Yang ; Weikang Hu ; Zihan Wang ; Wenjing Zhou ; Qingya He ; Jian Zhong ; Mingcong Li ; Li Liu ; Chaoyang Zhang ; Sumei Zhang ; Shengquan Zhang
Acta Universitatis Medicinalis Anhui 2025;60(9):1653-1660
Objective:
To investigate the effect of loss of function of lanosterol synthase( LSS) gene on intestinal function in a mouse model of non-alcoholic fatty liver disease( NAFLD) induced by a high-fat diet.
Methods:
LSS gene heterozygous knockout C57 mice ( LSS + / -) were established using the CRISRP / Cas9 system.After being fed a high-fat diet with 60% fat content for 6 months,the fat deposition in liver tissues was detected by HE and Oil red O staining,the morphological changes of small intestine tissue were detected by HE staining.The changes in total cholesterol content in intestinal tissue were detected by kits.The gastrointestinal motility function of mice was detected by phenol red paste.The intestinal permeability was detected by Evans blue staining,and the expression of LSS,tight junction protein ( Claudin) -1,Claudin-5,cluster of differentiation 36 ( CD36) ,and Niemann-Pick type C1-like 1 protein ( NPC1L1) proteins in small intestinal tissues were detected by Western blot.
Results :
The results of HE and Oil red O staining of liver tissues showed that liver fat deposition in LSS gene heterozygous knockout mice was lower than that in wild-type mice in the high-fat diet group.The total cholesterol content in intestinal tis- sue of LSS gene heterozygous knockout mice decreased ( P <0. 01) ,but no morphological differences were ob- served between the two groups of mice by HE staining of intestinal tissues.The gastrointestinal motility function of LSS gene heterozygous knockout mice did not show significant changes.The intestinal permeability of LSS gene het- erozygous knockout mice in the high-fat diet group decreased as detected by Evans blue ( P<0. 05) .The expres- sion levels of Claudin-5 protein in the intestinal tissue of LSS gene heterozygous knockout mice in the high-fat diet group increased ( P <0. 05 ) ,while the expression of LSS protein in the intestinal tissues of LSS heterozygous knockout mice decreased ( P <0. 05) .
Conclusion
In the NAFLD model induced by a high-fat diet,LSS gene heterozygous knockout reduces liver fat deposition induced by a high-fat diet and improves intestinal barrier function by regulating cholesterol metabolism in intestinal tissues and up-regulating the expression of Claudin-5.
6.Changes in behavior and spatial memory of C57BL/6J mice of different ages
Zhen Yang ; Hongmei Bai ; Weikang Hu ; Mingcong Li ; Xiaoli Jiang ; Chaoyang Zhang ; Zihan Wang ; Wenjing Zhou ; Qingya He ; Jian Zhong ; Shengquan Zhang
Acta Universitatis Medicinalis Anhui 2025;60(8):1410-1417
Objective :
To explore the changes in behavior and spatial memory of C57BL/6J female mice of different ages (youth , middle-aged , and elderly) .
Methods:
C57BL/6J female mice were divided into female youth group (YG group) , female middle-aged group ( MG group) and female elderly group ( OG group) according to age. The Morris water maze test measured spatial memory ability , and the open field and elevated cross maze test observed activity level and anxiety level. Western blot was used to determine the protein expressions of CREB , CaMKⅡ(pan) and CaMKⅡ(p) in the hippocampus of the brain tissues of female mice in each group.
Results:
Compared with the YG group , the weight of the MG group and the OG group significantly increased (P < 0. 01 , P < 0. 001) . Compared with the OG group , the third quadrant escape latency and the number of crossings in the YG group and MG group were shortened , and the difference was not statistically significant. Compared with the OG group , there was a statistically significant difference in the exercise speed in the open field of the YG group (P < 0. 01) , there was no significant difference in the movement speed in the open field of the MG group , the number of entries into the central zone significantly increased in the MG group ( P < 0. 05 ) , and there was no significant difference in the number of entries in the YG group (P > 0. 05) . Compared with the OG group , the YG group had a statistically significant difference in the elevated cross maze (P < 0. 05) , the MG group had no statistically signif- icant difference in the elevated cross maze , and the number of closed arm entries in the YG group and MG group significantly increased (P < 0. 001 , P < 0. 01) . Compared with the YG group , the relative expression level of CaMKⅡ(pan) in the OG group was statistically significant ( P < 0. 05 ) , while the relative expression level of CaMKⅡ(pan) in the MG group was not statistically significant ( P > 0. 05) .
Conclusion
With the increase of age , the weight of C57BL/6J female mice gradually increased , the activity level and desire to explore gradually de- creased , the spatial memory ability also declined , and the anxiety level and anxiety-like behavior increased. This study helps to reveal the effect of age on the activity level and cognitive function of females , and provides a refer- ence for studying cognitive and memory decline in older females.
7.Prevotella nigrescens exacerbates periodontal inflammation and impairs cognitive function in mice
Qi CHEN ; Tiantian XIA ; Yongqiang ZHOU ; Mingyang CHANG ; Nan HU ; Yanmei YANG ; Zhong LI ; Yue GAO ; Bin GU
Journal of Southern Medical University 2025;45(3):453-460
Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
8.The real world study of bulleyaconitine A combined with hot package in the treatment of KOA
Yuxin YANG ; Dujun MA ; Yujie BI ; Yuhao ZHOU ; Yinxiang WEN ; Qiuhui ZHONG
China Modern Doctor 2025;63(6):65-68
Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7%,which was significantly higher than 71.7%of control group(P<0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P<0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P<0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.
9.Effects of CO2 intracavitary laser combined with pelvic floor magnetic stimulation on surface electromyography of pelvic floor muscle and three-dimensional ultrasound parameters of pelvic floor in patients with female stress urinary incontinence
Tao HOU ; Li CHEN ; Shan HE ; Ping ZHOU ; Qijun ZHONG ; Xiaohu LI ; Hua ZHAO ; Yang CHEN ; Yanmei GUO
China Medical Equipment 2025;22(5):87-92
Objective:To investigate the effects of CO2 intracavitary laser combined with pelvic floor magnetic stimulation on surface electromyography(sEMG)values and pelvic floor three-dimensional ultrasound parameters in female patients with stress urinary incontinence(SUI).Methods:A prospective study was conducted on 92 female SUI patients treated at the outpatient department of Meizhou People's Hospital from October 2021 to July 2023.The patients were randomly divided into an observation group and a control group(n=46 each)using a random number table.Both groups received home-based pelvic floor muscle training.The control group additionally received pelvic floor magnetic stimulation,while the observation group was treated with CO2 intracavitary laser combined with pelvic floor magnetic stimulation.The urinary leakage status,treatment efficacy,pelvic floor muscle sEMG,pelvic floor three-dimensional ultrasound parameters,quality of life,and sexual quality of life were compared between the two groups.Assessments included the International Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF),the Incontinence Impact Questionnaire-Short Form(IIQ-7),and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire(PISQ-12).Results:1-hour leakage volume:0 g(observation group)vs.3 g(control group),24-hour leakage episodes:0 times(observation group)vs.0 times(control group),the observed differences were statistically significant(Z=-2.866,-2.355,P<0.05).Total effective rate:95.65%(observation)vs.58.70%(control),the observed differences were statistically significant(x2=4.083,P<0.05).Pelvic floor muscle sEMG(after treatment):Maximal fast contraction:(40.78±3.28)μV(observation)vs.(35.17±5.10)μV(control),Mean tonic contraction:(31.56±4.20)μV(observation)vs.(25.87±3.82)μV(control),Mean endurance contraction:(29.34±2.58)μV(observation)vs.(25.37±2.67)μV(control),all differences between the two groups were statistically significant(t=2.736,19.919,3.025,15.426,P<0.05).After treatment,both groups showed reductions in bladder neck descent(BND)during Valsalva maneuver,bladder-symphysis distance(BSD),urethral rotation angle(URA),and posterior vesicourethral angle(RVA).However,the observation group demonstrated significantly greater reductions compared to the control group(post-treatment data:observation group(24.30±3.21)mm,(2.34±0.23)mm,(56.40±5.87)°,(89.54±9.21)°;control group(26.21±3.48)mm,(3.57±0.35)mm,(60.29±6.45)°,(126.71±13.50)°.These differences were statistically significant(t=2.736,19.919,3.025,15.426,P<0.05).Similarly,both groups exhibited decreased scores on the ICIQ-SF and IIQ-7 scales,along with increased scores on the PISQ-12.Again,the observation group showed superior improvement,with statistically significant differences(t=11.478,13.168,6.631,P<0.05).Conclusion:On the basis of pelvic floor muscle training,CO2 intracavitary laser therapy combined with pelvic floor magnetic stimulation can effectively alleviate urinary incontinence symptoms in patients with female stress urinary incontinence(FSUI),enhance therapeutic efficacy,improve pelvic floor muscle strength and the stability of pelvic support structures,and promote quality of life and sexual function.
10.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.


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