Relationship between cerebrovascular variation and the occurrence and recurrence of cerebral infarction / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between cerebrovascular variation and the occurrence and recurrence of cerebral infarction, and provide a theoretical basis for the precise prevention and treatment of cerebral infarction.Methods:Totally 13 939 patients who underwent magnetic resonance imaging(MRI) and magnetic resonance angiography(MRA) examination at the Second Affiliated Hospital of Shandong First Medical University from January 2020 to December 2021 were grouped according to clinical symptoms combined with the imaging report, including 4 412 cases in the cerebral infarction group and 9 527 cases in the control group.2 048 patients in the cerebral infarction group were eventually enrolled in the study according to the inclusion and exclusion criteria, including 1 479 cases of initial cerebral infarction and 569 cases of recurrent cerebral infarction.SPSS 25.0 statistical software was used for data analysis.The χ2 test was used to compare the incidence of cerebral infarction with different cerebrovascular variations.Univariate analysis of suspected risk factors for recurrent cerebral infarction was performed with χ2 test, nonparametric test and t test.The binary logistic regression was used to analyze independent risk factors of recurrent cerebral infarction. Results:The incidence of cerebral infarction in the dual-system cerebrovascular variant patients, the single-system cerebrovascular variant patients, and the non-cerebrovascular variant patients were 40.9%, 30.7% and 31.8% respectively.The incidence of cerebral infarction in the dual-system cerebrovascular variant patients was the highest compared with those in the single-system cerebrovascular variant patients and the non-cerebrovascular variant patients (both P<0.05). The incidence rates of embryonic posterior cerebral artery, vertebral artery dominance, and bilateral common origin anterior cerebral arteries were 14.09%, 10.76% and 5.32%, respectively.The incidence of bilateral common origin anterior cerebral arteries in the cerebral infarction group was significantly higher than that in the control group and the difference was statistically significant.Patients with cerebral infarction who were familial aggregation ( OR=2.207, 95% CI=1.591-3.062), hyperhomocysteinemia ( OR=1.262, 95% CI=1.014-1.570), hypertension ( OR=1.461, 95% CI=1.114-1.918), diabetes mellitus ( OR=1.348, 95% CI=1.072-1.694), coronary heart disease ( OR=1.491, 95% CI=1.196-1.858) were more likely to recurrent cerebral infarction ( P<0.05), and patients with cerebral infarction had a significantly increased risk of recurrent cerebral infarction with age ( OR=1.031, 95% CI=1.020-1.042, P<0.05). Conclusion:Dual-system cerebrovascular variation and bilateral common origin anterior cerebral arteries are risk factors for cerebral infarction.

A Network Pharmacology Study on the Cervix Prescription for Treatment of Cervical Cancer.

Purpose: Based on the method of network pharmacology to explore the mechanism of the cervical prescription (CP) in the treatment of cervical cancer (CC). Methods: We obtained the active ingredients and potential targets in the CP from the literature and the systematic pharmacological analysis platform of traditional Chinese medicine (BATMAN-TCM); the database was used to search for targets related to cervical cancer and to map CP and targets; the core targets were screened, and the protein-protein interaction network (PPI) was constructed using the TCM compound-target network and STRING database. Gene ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) pathway enrichment analysis of overlapping targets were performed using DAVID 6.8 online tool. Results: The CP contains 2 active ingredients, corresponding to 301 nonreactive targets; 10 GO biological process related items and 73 signal pathways were obtained. Cell experiments confirmed that the medicated serum of CP could effectively inhibit the proliferation and invasion ability of Hela cells. Conclusion: This study provides valuable information for TCM researchers and clinicians to better understand the main therapeutic targets and therapeutic roles of herbal decoctions in clinical settings. The results of our study preliminarily clarified that the cervical prescription has an inhibitory effect on cervical cancer cells.

Circ_0061140 Facilitates Adenomyosis Progression by Upregulating LIN28B in vitro.

OBJECTIVES: The aim of our study was to explore the role of circular RNA_0061140 (circ_0061140) in adenomyosis progression and its associated mechanism. DESIGN: We first analyzed the expression pattern of circ_0061140 in endometrial tissues of adenomyosis patients (n = 27) and uterine fibroid patients (n = 15). Loss-of-function experiments were conducted to analyze the biological roles of circ_0061140 in regulating the viability, apoptosis, proliferation, migration, and invasion of endometrial epithelial cells. The downstream microRNA (miRNA)/messenger RNA (mRNA) axis of circ_0061140 was predicted by bioinformatics tool Starbase, and its working mechanism was verified by rescue experiments. METHODS: Cell viability, apoptosis, proliferation, invasion, and migration were assessed by cell counting kit-8 assay, flow cytometry analysis, 5-ethynyl-2'-deoxyuridine assay, transwell assay, and scratch test. The binding relationship between miR-141-3p and circ_0061140 or lin-28 homolog B (LIN28B) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0061140 expression was upregulated in adenomyosis patients. Circ_0061140 knockdown suppressed the viability, proliferation, invasion, and migration and triggered the apoptosis of endometrial epithelial cells. Circ_0061140 served as a miRNA sponge for miR-141-3p, and miR-141-3p silencing partly reversed circ_0061140 knockdown-induced effects in endometrial epithelial cells. miR-141-3p directly interacted with LIN28B mRNA. LIN28B overexpression partly diminished miR-141-3p overexpression-mediated influences in endometrial epithelial cells. Circ_0061140 knockdown downregulated LIN28B expression by elevating miR-141-3p level in endometrial epithelial cells. LIMITATIONS: The functional verification of circ_0061140/miR-141-3p/LIN28B axis was merely conducted in vitro. CONCLUSION: Circ_0061140 contributed to adenomyosis progression by binding to miR-141-3p to induce LIN28B expression in vitro.

CDK6 increases glycolysis and suppresses autophagy by mTORC1-HK2 pathway activation in cervical cancer cells.

Cervical carcinoma is a leading malignant tumor among women worldwide, characterized by the dysregulation of cell cycle. Cyclin-dependent kinase 6 (CDK6) plays important roles in the cell cycle progression, cell differentiation, and tumorigenesis. However, the role of CDK6 in cervical cancer remains controversial. Here, we found that loss of CDK6 in cervical adenocarcinoma HeLa cell line inhibited cell proliferation but induced apoptosis as well as autophagy, accompanied by attenuated expression of mammalian target of rapamycin complex 1 (mTORC1) and hexokinase 2 (HK2), reduced glycolysis, and production of protein, nucleotide, and lipid. Similarly, we showed that CDK6 knockout inhibited the survival of CDK6-high CaSki but not CDK6-low SiHa cervical cancer cells by regulation of glycolysis and autophagy process. Collectively, our studies indicate that CDK6 is a critical regulator of human cervical cancer cells, especially with high CDK6 level, through its ability to regulate cellular apoptosis and metabolism. Thus, inhibition of CDK6 kinase activity could be a powerful therapeutic avenue used to treat cervical cancers.

Qiu's Neiyi Recipe Regulates the Inflammatory Action of Adenomyosis in Mice via the MAPK Signaling Pathway.

BACKGROUND: The management of adenomyosis is challenging and limiting. Qiu's Neiyi recipe (Qiu) is a traditional Chinese medicine (TCM) prescription clinically used for endometriosis treatment in China, but the effect and mechanism of Qiu on adenomyosis are undefined. METHODS: An experimental adenomyosis model was induced in female neonatal ICR mice administrated with tamoxifen. The adenomyosis mice were divided into five groups: high-, middle-, and low-Qiu's group, danazol group, and model group. The mice just administrated with the solvent only (no tamoxifen or drugs) were served as the control group. After 28 days of administration, the body, uterine, spleen, and thymus weights of all mice were examined. Then, the myometrial infiltration and the expression of inflammatory factors were detected by histology examination, ELISA, and qRT-PCR in the uterus. In addition, the MAPK/ERK signaling pathway-related protein expression in adenomyosis mice was detected by immunohistochemical (IHC) staining, qRT-PCR, and western blotting. RESULTS: In experimental adenomyosis mice, Qiu treatment improved the symptoms of adenomyosis by reducing the myometrial infiltration and increasing the index of spleen and thymus. The elevated levels of IL-1ß, IL-6, and TNF-α in serum and uterus tissues of adenomyosis model mice were also decreased after Qiu treatment. The improvement of Qiu on the adenomyosis was achieved by inhibiting the activated MAPK/ERK signaling pathway, including reducing the mRNA and protein expressions of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 in the uterus tissues. CONCLUSION: Qiu alleviated the inflammatory reaction and uterus histological changes in mice with adenomyosis, and the potential mechanism is through the inhibition of the MAPK/ERK signaling pathway. Qiu may be a promising treatment for adenomyosis.

Knockdown of MIR9­3HG inhibits proliferation and promotes apoptosis of cervical cancer cells by miR­498 via EP300.

Cervical cancer is a serious gynecological cancer and one of the primary causes of mortality in female patients with cancer. Despite advances in cancer research, the molecular mechanism underlying cancer remains poorly understood. High levels of MIR9­3 host gene (HG) are associated with the occurrence and development of cervical cancer. However, the specific role of MIR9­3HG during the development of cervical cancer is unclear. In the present study, the expression of MIR9­3HG was silenced in C33A and SiHa cervical cancer cell lines. Proliferation and apoptosis were measured in these cells using 5­ethynyl­2'­deoxyuridine assay and flow cytometry, respectively. In addition, targeting microRNAs (miRs) of MIR9­3HG and mRNAs of miR­498 were predicted using public databases. The predicted interactions between these molecules were validated using RNA immunoprecipitation, RNA pull­down and luciferase reporter assays. Lastly, C33A cells transfected with short hairpin MIR­3HG alone or in combination with miR­498 inhibitor or PC­EP300 were subcutaneously injected into mice. The levels of miR­498, EP300 and Ki67 in tumor tissue were measured via reverse transcription­quantitative PCR or western blotting. MIR9­3HG knockdown inhibited the proliferation of cervical cancer cells, whilst promoting apoptosis. MIR9­3HG sponged miR­498 and inhibited its expression. Additionally, miR­498 interacted with EP300 and inhibited its expression. Transfection with miR­498 inhibitor significantly decreased apoptosis levels; this effect was abolished following EP300 silencing in vitro. In vivo, both miR­498 inhibition and EP300 overexpression reversed the inhibition of tumor growth mediated by MIR­3HG knockdown. MIR9­3HG promoted the proliferation cervical cancer cells via EP300 and miR­498. These in vitro and in vivo findings demonstrate the regulatory role of the MIR9­3HG/miR­498/EP300 axis in cervical cancer cell growth. Thus, the present study identified novel molecular targets for the diagnosis and treatment of cervical cancer and provided new insight into the pathogenesis of cervical cancer.

PIF1 Affects the Proliferation and Apoptosis of Cervical Cancer Cells by Influencing TERT.

INTRODUCTION: Cervical cancer is a common malignancy in female and it is a serious disease threatening women's lives. We aimed to explore whether PIF1 helicase expression could affect cell proliferation and apoptosis, and whether its mechanisms were related to the expression and activity of TERT. METHODS: Western blot analysis was used to detect the expressions of PIF1 and TERT in End1/E6E7, Hela, SiHa, Ca-Ski and C-33A cells and apoptosis-related proteins (Bax, Bcl-2 and Caspase-3). RT-qPCR and Western blot analysis determined the expressions of PIF1 and TERT after transfection. After transfection or cycloastragenol (CAG) treatment, the proliferation, apoptosis, cell cycle and telomerase TERT activity were analyzed by CCK-8 assay, flow cytometry analysis and ELISA assay. Co-immunoprecipitation assay was used to verify the interactions between PIF1 and TERT. RESULTS: The expressions of PIF1 and TERT in End1/E6E7, Hela, SiHa, Ca-Ski and C-33A cells were increased. As PIF1 and TERT expressions in C-33A cells showed the minimum increase, C-33A cells were chosen for the next study. PIF1 interference inhibited the proliferation, decreased the ratio of G2/M phase and promoted apoptosis of transfected cells, and PIF1 interference promoted the expressions of Bax and Caspase-3 and suppressed the Bcl-2 expression. Furthermore, PIF1 interference down-regulated the telomerase activity. The effect of PIF1 overexpression was opposite to that of PIF1 interference. Co-immunoprecipitation assay demonstrated that PIF1 could combine with TERT. CAG treatment effectively reversed the effect of PIF1 interference on proliferation, cycle and apoptosis of C-33A cells transfected with shRNA-PIF1. Moreover, CAG treatment increased the expressions of PIF1 and TERT. DISCUSSION: PIF1 helicase could promote the proliferation and suppress the apoptosis of cervical cancer cells by down-regulating the activity of telomerase TERT.

Chinese herbal medicine for premature ovarian insufficiency: A protocol for systematic review.

BACKGROUND: Premature ovarian insufficiency (POI) is the loss of function of the ovaries before age 40. Chinese herbal medicine (CHM) has been treating POI for long time. Therefore, we conduct this study to assess the efficacy and safety of CHM for POI. METHODS: Seven databases will be searched from inception to December 31, 2018: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), WanFang Database, and Chongqing Chinese Scientific Journal Database (CQVIP). Randomized controlled trials that used CHM will be included. Two reviewers will independently complete the study selection, data extraction, and study quality assessment according to Cochrane Collaboration. All the data will be analyzed using Review Manage 5.3 software. RESULTS: This study will generate a comprehensive summary on effectiveness and safety of CHM for POI. CONCLUSION: This study may be beneficial to health policymakers, clinicians, and patients with regard to the use of CHM in POI treatment. TRIAL REGISTRATION NUMBER: PROSPERO CRD 42019144629.

Recurrent ovarian hemorrhage in a patient with aplastic anemia: A case report.

RATIONALE: Recurrent ovarian hemorrhage resulting in ovarian infarction may lead to a life-threatening intraperitoneal hemorrhage in women with bleeding disorders such as aplastic anemia (AA). Moreover, it is seen as ovarian tumors in the diagnosis. The authors report a clinical case with the aim of sharing our experiences and exploring the ways to diagnose, treat, and avoid ovarian hemorrhage. PATIENTS CONCERNS: A 48-year-old woman with AA had suffered from a serious abdominal distension for the past 24 hours, which had occurred intermittently for the past 15 years. DIAGNOSES: Pelvic ultrasonography had revealed a large anechoic area of fluid in the abdomen without any sign of primary hemorrhage each time she had experienced an episode over the past 15 years. The volume of pelvic fluid had decreased after anti-inflammatory and hemostatic treatment. At presentation, the abdominal computed tomography suggested an ovarian tumor with a massive hemoperitoneum (a right ovarian mass, 5.7 × 5.0 × 5.0 cm in size, with a large amount of abdominal and pelvic fluid). INTERVENTIONS: Surgery was performed with respect to the bilateral uterine adnexa. On laparotomy, there were blood clots of approximately 6.0 × 6.0 × 5.0 cm surrounding the right ovary and approximately 400 mL bloody fluid in the abdomen. OUTCOMES: The patient recovered without incident and was transferred to a hematology ward 1 week later. Postoperative pathology confirmed hemorrhagic infarction of the right ovary. LESSONS: In conclusion, continuous ovarian bleeding can cause ovarian infarction to women with bleeding disorders and it may be confused with an ovarian tumor. Moreover, an earlier ovariectomy procedure under stable conditions or treatment with gonadotropin-releasing hormone that prevent bleeding via ovulation suppression may be effective for such cases.

Emodin Promotes Apoptosis of Human Endometrial Cancer Through Regulating the MAPK and PI3K/ AKT Pathways.

Emodin, a major component of rhubarb, has anti-tumor effects in a variety of cancers, influencing multiple steps of tumor development through modulating several signaling pathways. The aim of this study is to examine the effect of emodin on cell apoptosis and explore the underlying mechanisms in human endometrial cancer cells. Here we report that emodin can inhibit KLE cell proliferation and induce apoptosis in a time- and dose-dependent manner. Western blot assay found that emodin was involved in MAPK and PI3K/Akt signaling pathways. Specifically, emodin significantly suppressed the phosphorylation of AKT, and enhanced the phosphorylation of MAPK pathways. Furthermore, the generation of reactive oxygen species (ROS) was up-regulated in KLE cells upon treatment with emodin, while the anti-oxidant agent N-acetyl cysteine (NAC) can inhibit emodin-induced apoptosis and promote the activation of AKT and Bcl-2. Taken together, we revealed that emodin may induce apoptosis in KLE cells through regulating the PI3K/AKT and MAPK signaling pathways, indicating the importance of emodin as an anti-tumor agent.