2.Research Progress in the Role of Tamoxifen in Nervous System and Cognitive Function.
Jin-Nong WANG ; Yi TIAN ; Qing-Yi CAO
Acta Academiae Medicinae Sinicae 2023;45(2):334-340
		                        		
		                        			
		                        			Neurological diseases include a variety of neurodegenerative diseases and other brain damage diseases.The treatment schemes for neurological diseases are still in research.The existing clinical and basic studies have confirmed that traditional estrogen therapy has certain protective effect on the nervous system,while it increases the risk of breast or endometrial cancer.The emergence of the selective estrogen receptor modulators (SERMs) can avoid the above mentioned problems.The available studies have confirmed the protective effect of tamoxifen as a SERM on the nervous system.This paper reviews the role and functioning mechanisms of tamoxifen in the nervous system and cognitive function,aiming to provide guidance for the future application of tamoxifen in the treatment of neurological diseases and the improvement of cognitive function.
		                        		
		                        		
		                        		
		                        			Tamoxifen/therapeutic use*
		                        			;
		                        		
		                        			Selective Estrogen Receptor Modulators/therapeutic use*
		                        			;
		                        		
		                        			Cognition
		                        			;
		                        		
		                        			Nervous System
		                        			
		                        		
		                        	
3.Effects of bisphenol A and bisphenol analogs on the nervous system.
Chunxia LI ; Chen SANG ; Shuo ZHANG ; Sai ZHANG ; Hui GAO
Chinese Medical Journal 2023;136(3):295-304
		                        		
		                        			
		                        			Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.
		                        		
		                        		
		                        		
		                        			Receptors, Estrogen/metabolism*
		                        			;
		                        		
		                        			Estrogens
		                        			;
		                        		
		                        			Benzhydryl Compounds/pharmacology*
		                        			;
		                        		
		                        			Nervous System/metabolism*
		                        			
		                        		
		                        	
4.Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis.
Liu-Jun WU ; Yan CHEN ; Zi-Wei LIN ; Chen SUN ; Liang XIONG ; Xiao-Fang XIE ; Cheng PENG
China Journal of Chinese Materia Medica 2023;48(22):6093-6106
		                        		
		                        			
		                        			This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Estrogen Receptor alpha
		                        			;
		                        		
		                        			Oxytocin
		                        			;
		                        		
		                        			Dysmenorrhea/metabolism*
		                        			;
		                        		
		                        			Cyclooxygenase 2
		                        			;
		                        		
		                        			Dinoprostone
		                        			;
		                        		
		                        			RNA, Messenger/metabolism*
		                        			;
		                        		
		                        			Dinoprost
		                        			
		                        		
		                        	
5.Management of menopausal syndrome in women with dyslipidemia.
Yang Mei LI ; Xun LEI ; Li Li YU
Chinese Journal of Preventive Medicine 2023;57(11):1908-1914
		                        		
		                        			
		                        			The prevalence of dyslipidemia is increased in postmenopausal women due to dysregulation of lipid metabolism and deficiency of estrogen levels. At the same time, some postmenopausal women also have menopausal syndromes such as vasomotor symptoms, physical physiology, mental psychology, and urogenital tract atrophy. Menopausal hormone therapy is the most effective measure to alleviate menopausal syndrome. And initiating MHT in early menopause can reduce cardiovascular damage. However, menopausal hormone therapy can also bring the risk of thromboembolic diseases such as venous embolism, myocardial infarction and stroke. Different drug regimens have different effects on lipid metabolism. Women with menopausal syndrome should take individualized treatment plans for different types of dyslipidemia. Therefore, this article reviews the management and treatment of menopausal syndrome in women with dyslipidemia, so as to provide a reference for personalized management of dyslipidemia in postmenopausal women.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Menopause
		                        			;
		                        		
		                        			Estrogen Replacement Therapy
		                        			;
		                        		
		                        			Cardiovascular Diseases/epidemiology*
		                        			;
		                        		
		                        			Estrogens/pharmacology*
		                        			;
		                        		
		                        			Dyslipidemias/drug therapy*
		                        			
		                        		
		                        	
6.Guidelines for pharmaceutical care of endocrine therapeutics for breast cancer(2023 edition).
Chinese Journal of Oncology 2023;45(10):834-862
		                        		
		                        			
		                        			Endocrine therapy is one of the primary treatment methods for hormone receptor-positive breast cancer patients. As of June 1 2023, the National Medical Product Administration has approved 56 drugs related to endocrine therapy in patients with HR+ /HER-2- breast cancer (including generic drugs that have passed the consistency evaluation), including 44 endocrine drugs which can be categorized according to their mechanisms of action into selective estrogen receptor modulators, selective estrogen receptor down-regulators, aromatase inhibitors, luteinizing hormone-releasing hormone analogs, and progestogens and 12 targeted drugs for combined with endocrine therapy, including CDK4/6 inhibitors, mTOR inhibitors, and HDAC inhibitors. The different pharmacological characteristics, mechanisms of action, and long-term medication factors of breast cancer endocrine therapy-related drugs can directly affect patients' medication adherence and medication safety. To standardize the pharmaceutical care of endocrine therapy drugs for breast cancer and promote rational use in clinical settings, the Oncology Specialty Pharmacist Subcommittee, in conjunction with multidisciplinary experts nationwide, has developed the "Guidelines for pharmaceutical care of endocrine therapy drugs for breast cancer (2023 edition)". The guidelines is based on clinical evidence-based evidence, relevant regulations of pharmaceutical management, and pharmaceutical care practices. The Delphi method and expert interviews were used to formulate the guidelines. The GRADE approach was used for assessing the certainty of evidence. This guideline mainly focuses on endocrine therapy for HR+ /HER-2- breast cancer patients. Due to space constraints, HER-2 positive targeted drugs were not included in the guideline. It covers 6 dimensions and 22 key problems of pharmaceutical care in the whole process of drug therapy, providing a scientific basis for pharmacists to carry out pharmaceutical care of such drugs.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Breast Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Aromatase Inhibitors/therapeutic use*
		                        			;
		                        		
		                        			Receptors, Estrogen
		                        			
		                        		
		                        	
7.Management of menopausal syndrome in women with dyslipidemia.
Yang Mei LI ; Xun LEI ; Li Li YU
Chinese Journal of Preventive Medicine 2023;57(11):1908-1914
		                        		
		                        			
		                        			The prevalence of dyslipidemia is increased in postmenopausal women due to dysregulation of lipid metabolism and deficiency of estrogen levels. At the same time, some postmenopausal women also have menopausal syndromes such as vasomotor symptoms, physical physiology, mental psychology, and urogenital tract atrophy. Menopausal hormone therapy is the most effective measure to alleviate menopausal syndrome. And initiating MHT in early menopause can reduce cardiovascular damage. However, menopausal hormone therapy can also bring the risk of thromboembolic diseases such as venous embolism, myocardial infarction and stroke. Different drug regimens have different effects on lipid metabolism. Women with menopausal syndrome should take individualized treatment plans for different types of dyslipidemia. Therefore, this article reviews the management and treatment of menopausal syndrome in women with dyslipidemia, so as to provide a reference for personalized management of dyslipidemia in postmenopausal women.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Menopause
		                        			;
		                        		
		                        			Estrogen Replacement Therapy
		                        			;
		                        		
		                        			Cardiovascular Diseases/epidemiology*
		                        			;
		                        		
		                        			Estrogens/pharmacology*
		                        			;
		                        		
		                        			Dyslipidemias/drug therapy*
		                        			
		                        		
		                        	
8.Clinicopathological characteristics related to Miller/Payne grading system of breast carcinoma after neoadjuvant therapy and establishment of novel prediction models.
Wei HOU ; Qian YAO ; Dong Feng NIU ; Wei Cheng XUE
Chinese Journal of Pathology 2022;51(8):743-748
		                        		
		                        			
		                        			Objective: To investigate the correlation between clinicopathological features and Miller/Payne (MP) grading system of breast carcinoma after neoadjuvant treatment and to establish novel prediction models. Methods: A total of 1 053 cases of invasive breast carcinoma NOS that undertaken neoadjuvant treatment according to Guidelines of CSCO for Breast Cancer were selected at the Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute from September 2016 to September 2019, and the clinical, pathologic data, MP grading and immunohistochemical staining were evaluated. Statistical analysis was conducted using R software. Several novel computer models on prediction of MP grading were established and validated. Results: Among 1 053 patients who accepted neoadjuvant treatment, 316 patients (316/1 053, 30%) were evaluated as MP5 postoperatively, and 737 patients (737/1 053, 70%) did not meet MP5 level. MP5 had significant association with histological grade, ER and PR expression, HER2 status, Ki-67 index and molecular classification (P<0.05). Univariate/multivariate logistic regression analyses further showed that the above clinicopathological features were also independent influencing factors of MP5 grade; five-fold cross-validation was used to evaluate the performance of the models, and the sensitivity and specificity of different models were obtained. Conclusions: MP grading of invasive breast carcinoma NOS after neoadjuvant treatment is associated with high histological grade, negative ER and PR expression, HER2 positivity, high Ki-67 index and molecular classification, which are independent influence factors. GBM model recommended through comparison can provide some help for clinical diagnosis and treatment.
		                        		
		                        		
		                        		
		                        			Breast Neoplasms/pathology*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Ki-67 Antigen/metabolism*
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			;
		                        		
		                        			Neoplasm Grading
		                        			;
		                        		
		                        			Receptor, ErbB-2/metabolism*
		                        			;
		                        		
		                        			Receptors, Estrogen/metabolism*
		                        			;
		                        		
		                        			Receptors, Progesterone/metabolism*
		                        			
		                        		
		                        	
9.Diagnostic diversity and heterogeneity of tumors: a real-world study of metastasis re-biopsy in advanced breast cancer.
Huimin LV ; Limin NIU ; Mengwei ZHANG ; Huiai ZENG ; Shengnan ZHAO ; Min YAN
Chinese Medical Journal 2022;135(17):2076-2082
		                        		
		                        			BACKGROUND:
		                        			Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions.
		                        		
		                        			METHODS:
		                        			We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients' demographic profiles and disease characteristics.
		                        		
		                        			RESULTS:
		                        			In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies.
		                        		
		                        			CONCLUSIONS
		                        			The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Breast Neoplasms/metabolism*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Biomarkers, Tumor/metabolism*
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/pathology*
		                        			;
		                        		
		                        			Receptors, Progesterone/metabolism*
		                        			;
		                        		
		                        			Receptor, ErbB-2/metabolism*
		                        			;
		                        		
		                        			Receptors, Estrogen/metabolism*
		                        			;
		                        		
		                        			Biopsy
		                        			;
		                        		
		                        			Neoplasm Metastasis
		                        			
		                        		
		                        	
10.Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers.
Ofer BARANOVITCH ; Meirav WOLFF-BAR ; Meora FEINMESSER ; Chen SADE-ZALTZ ; Ilan TSARFATY ; Victoria NEIMAN
Journal of Integrative Medicine 2022;20(1):57-64
		                        		
		                        			OBJECTIVE:
		                        			We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients' repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.
		                        		
		                        			METHODS:
		                        			BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.
		                        		
		                        			RESULTS:
		                        			A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26-79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., "high-lipid Qi-like microscopic phlegm"), avoidance behavior which unconsciously uses "high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of "high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67).
		                        		
		                        			CONCLUSION
		                        			We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Breast Neoplasms
		                        			;
		                        		
		                        			Emotions
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Receptor, ErbB-2
		                        			;
		                        		
		                        			Receptors, Estrogen
		                        			;
		                        		
		                        			Receptors, Progesterone
		                        			
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail