Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

l-thyroxine attenuates extracellular Hsp90α-induced vascular endothelial calcification in diabetes mellitus, as revealed by parallel metabolic profiles.

BACKGROUND AND AIMS: Diabetic atherosclerotic vascular disease is characterized by extensive vascular calcification. However, an elevated blood glucose level alone does not explain this pathogenesis. We investigated the metabolic markers underlying diabetic atherosclerosis and whether extracellular Hsp90α (eHsp90α) triggers vascular endothelial calcification in this particular metabolic environment. METHODS: A parallel human/animal model metabolomics approach was used. We analyzed 40 serum samples collected from 24 patients with atherosclerosis and from the STZ-induced ApoE-/- mouse model. A multivariate statistical analysis of the data was performed, and mouse aortic tissue was collected for the assessment of plaque formation. In vitro, the effects of eHsp90α on endothelial cell calcification were assessed by serum analysis, Western blotting and immunoelectron microscopy. RESULTS: Diabetic ApoE-/- mice showed more severe plaque lesions and calcification damage. Stearamide, oleamide, l-thyroxine, l-homocitrulline and l-citrulline are biomarkers of diabetic ASVD; l-thyroxine was downregulated in both groups, and the thyroid sensitivity index was correlated with serum Hsp90α concentration. In vitro studies showed that eHsp90α increased Runx2 expression in endothelial cells through the LRP1 receptor. l-thyroxine reduced the increase in Runx2 levels caused by eHsp90α and affected the distribution and expression of LRP1 through hydrogen bonding with glutamine at position 1054 in the extracellular segment of LRP1. CONCLUSIONS: This study provides a mechanistic link between characteristic serum metabolites and diabetic atherosclerosis and thus offers new insight into the role of extracellular Hsp90α in promoting vascular calcification.

E3 Ubiquitin Ligase NEDD4L Negatively Regulates Skin Tumorigenesis by Inhibiting IL-6/GP130 Signaling Pathway.

IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.

Atypical mandibulofacial dysostosis with microcephaly diagnosed through the identification of a novel pathogenic mutation in EFTUD2.

BACKGROUND: Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients. METHODS: A patient with craniofacial anomalies was enrolled and evaluated by a multidisciplinary team. To make a definitive diagnosis, whole-exome sequencing was performed, followed by validation by Sanger sequencing. RESULTS: The patient presented with extensive facial bone dysostosis, upward slanting palpebral fissures, outer and middle ear malformation, a previously unreported orbit anomaly, and spina bifida occulta. A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease. CONCLUSIONS: We diagnosed this atypical case of MFDM by the detection of a novel pathogenetic mutation in EFTUD2. We also observed previously unreported features. These findings enrich both the genotypic and phenotypic spectrum of MFDM.

Two New Eudesmane-Type Sesquiterpene from Clonostachys sp. Y6-1and Their Cytotoxic Activity.

Two undescribed eudesmane-type sesquiterpenoids together with four known compounds were isolated from Clonostachys sp. Y6-1 associated. Their chemical structures were unambiguously determined by NMR, mass spectrometry, and 13 C-NMR calculation as well as DP4+ probability analyses. The absolute configurations of compounds 1 and 2 were determined by ECD calculation and X-ray single-crystal diffraction methods. Furthermore, all isolates were evaluated for in vitro cytotoxic activities against MCF-7, HCT-116, MDA-MB-231, and SW620 cancer cells. Among them, bioactivity evaluation of compound 5 revealed that weak activity (IC50 =66.55±0.82 µM) against SW620.

Quantum simulation of Hawking radiation and curved spacetime with a superconducting on-chip black hole.

Hawking radiation is one of the quantum features of a black hole that can be understood as a quantum tunneling across the event horizon of the black hole, but it is quite difficult to directly observe the Hawking radiation of an astrophysical black hole. Here, we report a fermionic lattice-model-type realization of an analogue black hole by using a chain of 10 superconducting transmon qubits with interactions mediated by 9 transmon-type tunable couplers. The quantum walks of quasi-particle in the curved spacetime reflect the gravitational effect near the black hole, resulting in the behaviour of stimulated Hawking radiation, which is verified by the state tomography measurement of all 7 qubits outside the horizon. In addition, the dynamics of entanglement in the curved spacetime is directly measured. Our results would stimulate more interests to explore the related features of black holes using the programmable superconducting processor with tunable couplers.

Cytotoxic sesquiterpene aryl esters from Armillaria gallica 012m.

Objective: To study the chemical constituents of the EtOAc extract of Armillaria gallica 012m. Methods: The chemical constituents of the EtOAc extract of A. gallica 012m were isolated and purified by various column chromatography and their structures were elucidated on the basis of the 1D and 2D NMR spectroscopic and HRESIMS data. Cytotoxicity of all isolates against A549, HCT-116, M231 and W256 human tumor cells was determined by the MTT method. Results: A new sesquiterpene aryl ester, armimelleolide C (1), and eight known ones including armillarivin (2), melleolide F (3), 6'-chloromelleolide F (4), melleolide (5), melleolide K (6), melledonol (7), 13-hydroxydihydromelleolide (8), and armillane (9), were isolated from the EtOAc extract of A. gallica 012m. All isolates showed potential cytotoxic activities against at least one of the human cancer cell lines with IC50 values ranging from (3.17 ± 0.54) to (17.57 ± 0.47) µmol/L. Compound 1 showed significant inhibitory activity against M231 with an IC50 value of (7.54 ± 0.24) µmol/L compared with paclitaxel as the positive control. Compounds 2, 3, and 7, 9 showed obvious inhibitory activity against HCT-116 and were better than that of the positive control. Conclusion: The chemical constituents including a new sesquiterpene aryl ester armimelleolide C (1) from the EtOAc extract of A. gallica 012m have a variety of structures and potential antitumor activities.

The breakdown of both strange metal and superconducting states at a pressure-induced quantum critical point in iron-pnictide superconductors.

Here we report the first observation of the concurrent breakdown of the strange metal (SM) normal state and superconductivity at a pressure-induced quantum critical point in Ca10(Pt4As8)((Fe0.97Pt0.03)2As2)5 superconductor. We find that, upon suppressing the superconducting state, the power exponent (α) changes from 1 to 2, and the slope of the temperature-linear resistivity per FeAs layer (A□) gradually diminishes. At a critical pressure, A□ and superconducting transition temperature (Tc) go to zero concurrently, where a quantum phase transition from a superconducting state with a SM normal state to a non-superconducting Fermi liquid state occurs. Scaling analysis reveals that the change of A□ with Tc obeys the relation of Tc ~ (A□)0.5, similar to what is seen in other chemically doped unconventional superconductors. These results suggest that there is a simple but powerful organizational principle of connecting the SM normal state with the high-Tc superconductivity.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

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.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

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 (HRage 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 (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung 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 (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung 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.

Stability Analysis and Optimal Control Strategies of an Echinococcosis Transmission Model.

This paper presents a deterministic compartmental model for echinococcosis transmission dynamics. The basic reproduction number of the model determines the existence and stability of the disease-free and disease-endemic equilibrium points. We further formulate the optimal control problem and obtain the necessary conditions to minimize the number of infected individuals and the associated costs. Numerical simulations show that optimal control strategies can significantly reduce the number of infected individuals to lower levels. Environmental disinfection may be essential for the elimination of infections. The results of this study will be beneficial for the prevention and control of echinococcosis in the Ganzi Tibetan Autonomous Prefecture and other areas of China.

[Disease Characteristics, Treatment, and Prognosis of Chinese Patients with Autoimmune Encephalitis: A Retrospective Study].

OBJECTIVE: To investigate the clinical features and prognosis of autoimmune encephalitis (AE). METHODS: Accessing data from the electronic medical records of patients receiving care at West China Hospital, Sichuan University, China between 2013 and 2019, we conducted a retrospective study of the disease characteristics, laboratory examinations, treatment, and prognosis of AE patients. Before they were discharged, modified Rankin Scale (mRS) was used to assess the prognosis of AE patients and their mRS scores were then used to categorize patients as having good prognosis (mRS scores of 0-2) or poor prognosis (mRS scores of 3-6). Multivariate logistic regression was used to analyze risk factors associated with poor prognosis. RESULTS: A total of 121 patients were included in the study. The male-to-female ratio was 1∶1.1. At the time of diagnosis, patients were mainly from the age group of young to middle-aged individuals. Among the 121 patients, 64.5% (78 patients) had anti-N-methyl D-aspartate receptor (NMDAR) encephalitis, accounting for the largest proportion. 33.1% (40 patients) first visited the Department of Psychiatry for medical assistance. 62.8% (76 patients ) showed prodromal symptoms. The common clinical manifestations of the AE patients at the time of admission included cognitive dysfunction (104 patients, 86.0%), thought disorder (90 patients, 74.4%), and altered behaviors (88 patients, 72.7%). The NMDAR antibody titers were higher in the cerebrospinal fluid (CSF) than those in the serum. Double-positive antibodies were detected in 6 patients. No abnormality was observed in the brain magnetic resonance imaging (MRI) of 42 patients (34.7%) . Electroencephalography abnormalities were observed in 71 patients (58.7%). 111 patients (91.7%) received first-line immunotherapy and 61 patients (50.4%) still had neuropsychiatric deficits when they were discharged. Multivariate logistic regression revealed that consciousness disorder (odds ratio [ OR] =4.230, 95% confidence interval [ CI] : 1.540-11.617; P=0.005), altered behavior ( OR=2.997, 95% CI: 1.068-8.406; P=0.037) and movement disorder ( OR=7.753, 95% CI: 1.446-41.578; P=0.017) were risk factors for poor clinical prognosis of AE patients. CONCLUSIONS: Patients with AE mainly manifest cognitive damage. Half of the patients left neuropsychiatric deficits. The relationship between CSF titers and serum titers is unparalleled. The options of immunotherapy show no difference in their influence on prognosis. Cognitive dysfunction, altered behavior and movement disorder are independent risk factors for a poor prognosis at discharge.

Cardiac inflammation and fibrosis following chemo/radiation therapy: mechanisms and therapeutic agents.

The incidence of cardiovascular disorders is one of the most concerns among people who underwent cancer therapy. The heart side effects of cancer therapy may occur during treatment to some years after the end of treatment. Some epidemiological studies confirm that heart diseases are one of the most common reasons for mortality among patients that were received treatment for cancer. Experimental studies and also clinical investigations indicate that inflammatory changes such as pericarditis, myocarditis, and also fibrosis are key mechanisms of cardiac diseases following chemotherapy/radiotherapy. It seems that chronic oxidative stress, massive cell death, and chronic overproduction of pro-inflammatory and pro-fibrosis cytokines are the key mechanisms of cardiovascular diseases following cancer therapy. Furthermore, infiltration of inflammatory cells and upregulation of some enzymes such as NADPH Oxidases are a hallmark of heart diseases after cancer therapy. In the current review, we aim to explain how radiation or chemotherapy can induce inflammatory and fibrosis-related diseases in the heart. We will explain the cellular and molecular mechanisms of cardiac inflammation and fibrosis following chemo/radiation therapy, and then review some adjuvants to reduce the risk of inflammation and fibrosis in the heart.

Two new sesquiterpene aryl esters from Armillaria gallica 012m.

Two new sesquiterpene aryl esters, armimelleolides A and B (1 and 2), and four known ones, were isolated from the EtOAc extract of Armillaria gallica 012 m by column chromatography on silica gel, reversed-phase C18 silica gel and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods, including extensive 1 D NMR, 2 D NMR and MS. All these compounds showed potential antitumor activities against at least one of the human cancer cell lines (A549, HCT-116, M231 and W256), with IC50 ranging from 2.57 to 19.94 µM.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

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.

Unusual presentation of a first branchial arch fistula with maxillofacial infection: a case report.

BACKGROUND: First branchial cleft anomaly (FBCA) is a rare congenital defect that arises due to incomplete closure of the ventral portion of the first and second branchial arches. There are variable complex clinical manifestations for patients with FBCA, which are prone to misdiagnosis and inadequate treatment. FBCAs usually involve the facial nerve with a consequent increased risk of facial nerve damage. Here, we present an unusual case of FBCA presenting with two preauricular pits in association with an abnormal maxillofacial cyst. CASE PRESENTATION: A 10-month-old girl presented to our department due to recurrent maxillofacial infections accompanied by swelling or abscess of the left cheek and purulent discharge from the preauricular pit for 4 months. A 3D-computed tomography (CT) fistulogram and magnetic resonance imaging (MRI) revealed two conjunctive tract lesions: one tract arose from the skin surface anteroinferior to the external auditory canal (EAC), through the deep lobe of the left parotid, and anteriorly extended to the left masseter; the other extended from the superficial lobe of the left parotid to the intertragic notch. After the maxillofacial infection was controlled by intravenous antibiotic administration, surgery was performed. Intraoperative tools, such as facial nerve monitors, microscopes, and methylene blue dyes, were used to facilitate the complete dissection and protection of the facial nerve. On follow-up over one year, the patient recovered well without facial palsy or recurrence. CONCLUSION: FBCA with maxillofacial cysts is rare and prone to misdiagnosis. Physicians should pay attention to this anatomic variant of FBCA with the fistula track located deep inside the facial nerve and projected medially to the masseter.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms.

BACKGROUND: Poorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated. AIM: To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs. METHODS: The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively. RESULTS: Among the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs. CONCLUSION: The overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other patients.

Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination.

Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K-AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53-Nedd4-Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.

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.