AR Expression Correlates with Distinctive Clinicopathological and Genomic Features in Breast Cancer Regardless of ESR1 Expression Status.

Androgen receptor (AR) expression is frequently observed in breast cancer, but its association with estrogen receptor (ER) expression in breast cancer remains unclear. This study analyzed the clinicopathological and molecular features associated with AR negativity in both ER-positive and ER-negative breast cancer, trying to elucidate the molecular correlation between AR and ER. Our results showed that AR negativity was associated with different clinicopathological characteristics and molecular features in ER-positive and ER-negative breast cancer. Moreover, AR-positive breast cancer has better clinicopathological features than AR-negative breast cancer, especially in the ER-negative subtype. These results suggest that the role of AR in ER-negative breast cancer is distinctive from that in ER-positive breast cancer.

Common carotid artery thrombosis and malignant middle cerebral artery infarction following ovarian hyperstimulation syndrome: A case report.

BACKGROUND: Arterial thrombosis is a serious and rare complication of ovarian hyperstimulation syndrome (OHSS). Herein, we describe a case of OHSS complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction after egg retrieval and before embryo transfer. CASE SUMMARY: A 32-year-old female with a family history of thrombosis who was undergoing in vitro fertilization due to unexplained infertility, was admitted due to abdominal distension for 3 d and coma for 2 h. She received egg retrieval 7 d ago and embryo transfer had not yet been performed. Blood biochemical analysis showed estrogen of 15781 pmol/L. Gynecological examination showed palpable masses on both sides of the adnexal areas. Ultrasound observed enlarged ovaries and abdominal ascites. Imaging examination of the head and neck revealed fresh malignant middle cerebral artery infarction in the left side of brain and internal carotid artery as well as occlusion in the left carotid artery, internal carotid artery, and middle cerebral artery. The patient was finally diagnosed with severe OHSS, complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction. Liquid replacement, anticoagulation, vascular endothelium protection, brain protection and decompressive craniectomy were carried out. Rehabilitation training was then performed for 6 mo. At present, she has poor speaking ability and decreased muscle strength on the right side. CONCLUSION: There is a risk of thrombosis during any period of OHSS. During in vitro assisted reproduction, for cases with a family history of thrombosis, hyperlipidemia and other high-risk factors, serum lipid levels should be controlled as soon as possible to improve metabolic dysfunction. When thrombosis occurs, timely and effective treatment should be performed to improve the prognosis.

Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer.

In estrogen receptor (ER)-positive breast cancer, changes in biomarker expression after neoadjuvant therapy indicate the therapeutic response and are prognostic. However, there is limited information about the biomarker alteration caused by neoadjuvant endocrine therapy in ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We recruited ER-positive/HER2-negative breast cancer patients who received neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET), or sequential neoadjuvant endocrine-chemotherapy (NECT) at Peking University Cancer Hospital from 2015 to 2021. A total of 579 patients had paired immunohistochemistry information in both diagnostic biopsy samples and post-neoadjuvant therapy surgical samples. Through a paired comparison of the immunohistochemical information in pre-treatment and post-treatment samples, we found that progesterone receptor (PR) expression reductions were more frequent than ER expression reductions (70.8% vs. 35.2%) after neoadjuvant therapy. The percentage of patients who had a decreased Ki-67 index in the post-operative samples was similar in the three groups (79.8% vs. 79.7% vs. 78.4%). Moreover, PR losses caused by NET were related to low baseline PR expression (p = 0.001), while we did not find a significant association between PR losses and Ki-67 reductions (p = 0.428) or ER losses (p = 0.274). All three types of neoadjuvant therapies caused a reduction in ER, PR, and Ki-67 expression. In conclusion, we found that PR loss after NET was only significantly related to low baseline PR expression, and there is no significant difference in the extent of prognostic factor change including Ki-67 and ER between the PR loss and non-loss groups.

Analysis of chromosomes and the T helper 17 and regulatory T cell balance in patients with recurrent spontaneous abortion.

The present study investigated the genetic etiology and possible immunological pathogenesis of recurrent spontaneous abortion by analyzing chromosome abnormalities, and the balance between T helper 17 (Th17) and regulatory T (Treg) cells. A total of 54 patients with recurrent spontaneous abortion were selected. The villus and decidual tissues, and peripheral venous blood were collected from each patient. Villus chromosome analysis was performed by high-throughput gene sequencing. Flow cytometry was used to detect Th17 and Treg cells in patients without chromosome abnormalities (n=30) and the control group (normal pregnancy; n=32). Immunoglobulin (IG) combined with human chorionic gonadotropin hormone (HCG) treatment was given to patients without chromosome abnormalities (n=30). Changes in the expression levels of Th17 and Treg cells before and after treatment were compared with patients with successful pregnancy (n=18). Before treatment, compared with the control group, the proportion of Th17 cells in peripheral blood and decidual tissue was increased and the proportion of Treg cells decreased. After treatment, compared with patients before treatment, the proportion of Th17 cells decreased and Treg cells increased, and the Th17 and Treg cells balance was reversed with a biased towards Treg cells. The present results suggested that the Th17 and Treg cell immune imbalance may be an important immune factor in recurrent spontaneous abortion. IG combined with HCG therapy may improve pregnancy outcomes by reversing the imbalance between Th17 and Treg cells.

Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2- Breast Cancer.

In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed "the nearest-neighbor method" to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quantification of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and flow cytometry (r2 = 0.98). High ERα ENR was significantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4-11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2- BC indicates decreased likelihood of benefiting from ET.

Effect of GnRHa on Th17/Treg cells in peripheral blood of patients with unexplained repeated implantation failure.

OBJECTIVE: To investigate the effect and possible mechanism of downregulation of gonadotropin-releasing hormone agonist (GnRHa) on Th17/Treg (regulatory T cell) cells in peripheral blood of patients with unexplained repeated implantation failure (RIF). METHODS: Fifty-two patients who had RIF (≥ 3 consecutive transfers of ≥ 4 high-grade embryos in women under the age of 40 (excluding 40)) of frozen-thawed embryos were studied. Twenty-nine cases receiving simple hormone replacement therapy (HRT) were defined as transfer group, and the remaining 23 cases with HRT combined with GnRHa downregulation were defined as GnRHa downregulation group. In addition, 30 cases of the normal early pregnancy group were selected as control group. RESULTS: Before HRT, the number of Th17 and Treg cells in CD4+ lymphocytes was increased and decreased, respectively, with the ratio of Th17/Treg cells increased in HRT group compared with the control group (p < 0.05). On the day of progesterone conversion, compared with the HRT group, the percentage of Th17 and Treg cells was decreased and increased, respectively, with the ratio of Th17/Treg cells decreased significantly in GnRHa downregulation group (p < 0.05). The estrogen E2 levels of the GnRHa downregulation group were slightly higher than those of the HRT group, with no significant difference between the two groups (p > 0.05). Further, there was no significant difference in the levels of chorionic gonadotropin at the 14th day and the 21st day after transplantation between HRT group and GnRHa downregulation group (p > 0.05). CONCLUSION: There were an increase and a decrease in the number of Th17 and Treg cells, respectively, with Th17/Treg cells imbalanced in unexplained RIF. GnRHa downregulation may play a direct immunomodulatory role in disrupting the imbalance and then improve the endometrial receptivity. These effects did not depend on the E2 levels in peripheral blood, nor affect early embryonic development.

Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy.

CRISPR/Cas9 system is a powerful toolbox for gene editing. However, the low delivery efficiency is still a big hurdle impeding its applications. Herein, we report a strategy to deliver Cas9-sgPlk-1 plasmids (CP) by a multifunctional vehicle for tumor therapy. We condensed CPs on TAT peptide-modified Au nanoparticles (AuNPs/CP, ACP) via electrostatic interactions, and coated lipids (DOTAP, DOPE, cholesterol, PEG2000-DSPE) on the ACP to form lipid-encapsulated, AuNPs-condensed CP (LACP). LACP can enter tumor cells and release CP into the cytosol by laser-triggered thermo-effects of the AuNPs; the CP can enter nuclei by TAT guidance, enabling effective knock-outs of target gene (Plk-1) of tumor (melanoma) and inhibition of the tumor both in vitro and in vivo. This AuNPs-condensed, lipid-encapsulated, and laser-controlled delivery system provides a versatile method for high efficiency CRISPR/Cas9 delivery and targeted gene editing for treatment of a wide spectrum of diseases.

[Progress of studies on the mechanism of acupuncture treatment of acute ischemic cerebral stroke].

In the present paper, the authors review the current development of studies on mechanisms of acupuncture treatment of acute ischemic cerebral apoplexy from (1) blood rheology, (2) cerebral microcirculation, 3) metabolism of cerebral tissue, (4) cerebral electrical activity, (5) free radicals and lipid peroxidation reaction, (6) excitatory aminoacid, (7) calcium overload, (8) nitrogen monoxidum, and (9) cerebral apoptosis. Cerebral stroke includes ischemic stroke and hemorrhagic stroke. Ischemic cerebral stroke accounted for about 60%-70% of all the stroke cases. At present, the main remedies for treating acute ischemic cerebral stroke includes thrombolysis, anti-platelet aggregation, improving microcirculation and symptomatic therapy. In stroke, highlighting the efficacy of acupuncture therapy in the treatment of stroke.