1.Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer
Feng XU ; Kun XU ; Lingling FAN ; Xintong LI ; Yiqiu LIU ; Fang YANG ; Chengjun ZHU ; Xiaoxiang GUAN
Chinese Medical Journal 2024;137(3):338-349
Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.
2.Comparison of remazolam and midazolam for sedation of synchronous electrical cardioversion
Lingling CHEN ; Ren GUAN ; Muting LU ; Qiyin ZHANG
The Journal of Clinical Anesthesiology 2024;40(6):617-620
Objective To compare the sedative effect and safety of remimazolam and midazolam in synchronous electrical cardioversion in patients with atrial fibrillation.Methods Thirty-two patients with at-rial fibrillation receiving synchronous electrical cardioversion from January 2021 to December 2022 were en-rolled,22 males and 10 females,aged 18-80 years,BMI 20-30 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were randomly divided into two groups using random number table method:remimazolam group and midazolam group,16 patients in each group.The remimazolam group was sedated with 0.2 mg/kg of intra-venous remimazolam,and the midazolam group was sedated with 0.025 mg/kg of midazolam intravenously,and the drug injection time in both groups was 1 min.The anesthesia onset time,awakening time,and ori-entation recovery time were recorded.SBP,DBP,and SpO2 were recorded before anesthesia induction(T,),when the eyelash reflex was absent(T2),after the completion of electrical cardioversion(T3),and at the time of awakening(T4).Neurobehavioral cognitive state examination(NCSE)was performed 5 mi-nutes after the patients were awake,including language ability,structural ability,memory,calculation abil-ity and reasoning ability,and the pass rate of each ability test was calculated.The occurrence of adverse re-actions during surgery(body movement,apnea)and within 12 hours after surgery(nausea,vomiting,and chest pain)was recorded.Results Compared with the midazolam group,the anesthesia onset time,awak-ening time,and orientation recovery time in the remimazolam group were significantly shortened(P<0.05).There was no significant difference in SBP,DBP,and Sp02 between the two groups at different time points.Compared with the midazolam group,the pass rate of the reasoning ability test was higher in the remimazolam group 5 minutes after awakening(P<0.05).There was no significant difference in the inci-dence of adverse reactions between the two groups.Conclusion Compared with midazolam,remimazolam has faster onset of sedation,faster awakening,faster recovery of orientation in synchronous electrical cardio-version of atrial fibrillation,and faster recovery of reasoning ability in NCSE after synchronous electrical car-dioversion.
3.Correlation analysis of apparent diffusion coefficient combined with C-reactive protein on delayed encephalopathy caused by carbon monoxide poisoning
Chen LI ; Min WANG ; Menglin LIANG ; Yanyun GUAN ; Lingling LIU ; Wei ZHANG ; Yubo LIU ; Jiarui XU ; Baobao FENG ; Xingguo ZHANG
Chinese Journal of Emergency Medicine 2023;32(3):327-331
Objective:To investigate the Correlation between ADC combined with serum C-reactive protein (CRP) and delayed encephalopathy after carbon monoxide poisoning (DEACMP), It provides scientific basis for early prediction of DEACMP.Methods:According to the design principle of case-control study, the data of acute carbon monoxide poisoning (ACOP) patients admitted to Shandong Provincial Hospital from December 2017 to December 2021 were retrospectively selected. Among them, patients with DEACMP were selected as the case group, without DEACMP were used as the control group. Univariate and multivariate analyses were performed on the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of ADC combined with CRP as a combined predictor for disease.Results:A total of 89 patients with ACOP were included, including 33 patients with DEACMP and 56 patients without DEACMP. There were no significant differences in gender, age, smoking, drinking, and underlying diseases (hypertension, coronary heart disease) between groups ( P>0.05). Logistic regression analysis showed that white blood cell count (WBC) ( OR=1.64, 95% CI: 1.19-2.26, P=0.003), CRP ( OR=1.22, 95% CI: 1.03-1.45, P=0.019) and ADC value of central semiovale white matter ( OR=0.99, 95% CI: 0.98-1.00, P=0.010) were associated with DEACMP in patients with ACOP. The ROC curve results showed that the area under the ROC of ADC combined with CRP in the center of semiovale was 0.765 (95% CI: 0.656-0.845), the specificity was 87.9%, the sensitivity was 23.2%, and the cut-off value was 3.5°. Conclusions:WBC, CRP and ADC value of central semiovale are independent factors for DEACMP. ADC value of central semiovale combined with CRP has more clinical value in the early diagnosis of DEACMP. For ACOP patients with DEACMP triggering factors, the diagnosis and treatment awareness of early screening of brain magnetic resonance imaging should be strengthened to avoid DEACMP.
4.Clinicopathological features of clear cell hidradenoma in 23 cases
Lingling WU ; Yan XIA ; Yang FENG ; Xuehan WANG ; Jingwen GUAN ; Xuan WU ; Xiaoshuang WANG
Chinese Journal of Primary Medicine and Pharmacy 2022;29(7):1054-1058
Objective:To investigate the clinicopathological features, immunophenotype and differential diagnosis of clear cell hidradenoma, and to analyze the origin of clear cell hidradenoma and the underlying mechanism.Methods:The clinical data of 23 cases of clear cell hidradenoma who underwent surgical resection in Suzhou Municipal Hospital between December 2017 and July 2021 were retrospectively analyzed. Clinical manifestation, imaging features, pathological features and prognosis of the 23 cases of clear cell hidradenoma were analyzed. Expression levels of epithelial membrane antigen, cytokeratin 20, cytokeratin 7, cytokeratin 14, carcinoembryonic antigen, and gross cystic disease fluid protein 15 were detected by immunohistochemical staining technique using the EnVision system. Periodic acid-Schiff (PAS) staining was performed to visualize glycogen.Results:Among the 23 cases, 8 were male and 14 were female, aged 14-94 years, with a median age of 55 years. The first symptom of clear cell hidradenoma was epidermal bulgels in 18 cases.Contrast ultrasonography showed a subcutaneous cystic solid echo mass with abundant blood flow in the solid part. The tumor histologically consisted of two types of cells: secretory epithelial cells or glandular epithelial cells and clear cells. Twenty cases had tumors with the features of benign clear cell hidradenoma. Two cases had atypical clear cell hidradenoma with atypia and mitosis. One case had malignant clear cell hidradenoma. Tumor cells were positive for epithelial membrane antigen, cytokeratin 7, cytokeratin 14, carcinoembryonic antigen, and gross cystic disease fluid protein 15 and they were Periodic acid-Schiff-positive. Twenty-three patients were followed up for 2-36 months, of which 4 were lost to follow-up and the rest had no recurrence of clear cell hidradenoma.Conclusion:Clear cell hidradenoma is rare and has a good prognosis. Malignant clear cell hidradenoma is rarer and has a poor prognosis. Diagnosis of clear cell hidradenoma is mainly based on comprehensive analysis of pathological features and immunophenotypes. Clear cell hidradenoma should be differentiated from metastatic clear cell carcinoma, spiral adenoma, cortical adenoma, and malignant melanoma.
5.Effects of liver -specific knockout of transcription factor EB on diet -induced hepatic steatosis in mice
Lingling Guan ; Daichuan Cheng ; Heng Zhang ; Xiuli Men
Acta Universitatis Medicinalis Anhui 2022;57(12):1875-1879
Objective :
To explore the effect of liver-specific knockout of transcription factor EB (Tfeb) on high-fat diet ( HFD ) -induced hepatic steatosis in mice.
Methods :
Wild-type C57BL /6J mice and liver-specific Tfeb knockout C57BL /6J mice were fed with HFD or normal chow for 12 weeks,respectively,and then the serum tri- glyceride (TG) ,total cholesterol ( TC) ,monocyte chemoattractant protein-1 ( MCP-1 ) ,tumor necrosis factor-α (TNF-α) ,aspartate aminotransferase ( AST) and alanine transaminase ( ALT) were measured in each group of mice ; Western blot was used to detect Tfeb protein expression levels in liver tissues of mice in each group,HE stai- ning was used to monitor histopathological changes in liver tissues of mice in each group,oil red O staining was used to monitor lipid deposition in liver tissues of mice in each group,and F4 /80 fluorescence staining was used to monitor macrophage infiltration in liver tissues of mice in each group.
Results :
There was no expression of Tfeb gene in liver of liver-specific knockout Tfeb mice,suggesting that the effect of Tfeb gene knockout in liver tissue was better.Compared with the normal control group,the expression of Tfeb protein in the liver tissue of the model control group was down-regulated.Compared with the normal control group,both the HE staining results and the oil red O staining results showed that the liver specific Tfeb caused lipid deposition and liver lobule disorder in mice, which was similar to the liver changes in the model control mice,however,liver-specific knockout of Tfeb mice at 12 weeks of HFD had more severe liver lipid deposition and hepatic lobular structural disorder.The results of F4 / 80 fluorescence staining indicated that the specific knockout of liver Tfeb could aggravate the infiltration of macro- phages in the liver of mice induced by high-fat feeding.At the same time,the serological test results indicated that compared with the normal control group,the serum levels of TC,TG,TNF-α , MCP-1,AST and ALT in the liver- specific knockout Tfeb group and the model control group increased ,and these changes were further elevated in Tfeb knockout mice after HFD feeding.
Conclusion
Liver-specific knockout of Tfeb aggravates HFD-induced he- patic steatosis in mice.
6.Protective factors of psychological resilience in patients with inflammatory bowel disease based on the Kumpfer model: a qualitative study
Lili YOU ; Yangyang WANG ; Siyao WANG ; Lingling ZHU ; Tiantian WANG ; Xiang YU ; Yifeng ZHANG ; Jing DONG ; Yuxia GUAN
Chinese Journal of Modern Nursing 2022;28(6):732-738
Objective:To explore the protective factors of psychological resilience in patients with inflammatory bowel disease (IBD) , so as to provide a basis for improving the psychological resilience of patients.Methods:From December 2020 to March 2021, 16 IBD patients in the Department of Gastroenterology of Peking Union Medical College Hospital were selected as the research object by purpose sampling, and the semi-structured in-depth interview was conducted with them. The interview data was organized and analyzed using the directed content analysis method.Results:A total of 3 themes and 10 sub-themes were extracted, including internal characteristics of individuals, social support network, environmental perception and active transformation. Among them, the internal characteristics of individuals included calm acceptance of the disease, positive disease cognition, appropriate emotion regulation, and clear goal motivation. Social support network consisted of solid family support, professional medical care, stable relationships, normal work status. Environmental perception and active transformation comprised selective perception of the environment and active behavioral coping.Conclusions:Medical and nursing staff should cooperate with the patient's family, friends and other parties to implement cognitive intervention, perfect the support system, and promote positive behaviors, thereby improving the patients' psychological resilience.
7.Effects of Microbiota on the Treatment of Obesity with the Natural Product Celastrol in Rats
Weiyue HU ; Lingling WANG ; Guizhen DU ; Quanquan GUAN ; Tianyu DONG ; Ling SONG ; Yankai XIA ; Xinru WANG
Diabetes & Metabolism Journal 2020;44(5):747-763
Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity. We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol. We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 µg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.
8.Pertussis antibody titers in pregnant women's venous blood and cord blood—a survey from three women and children's hospitals in Beijing
Chi LI ; Jiuye GUO ; Li GUAN ; Fangfang GUO ; Rong MI ; Jin FU ; Xiaodai CUI ; Fei XIAO ; Guanfu MA ; Yanyu LYU ; Shanshan GENG ; Lingling DENG ; Yun CHENG ; Dongmei FU ; Guiyun WANG
Chinese Journal of Neonatology 2019;34(5):338-342
Objective To study the levels of antibodies against bordetella pertussis among pregnant women and neonates in Beijing. Method From December 2016 to March 2017, pregnant women and their newborns from three women and children′s hospitals in Beijing were enrolled in this study. 3 ml of venous blood from the mothers and 3 ml of umbilical cord blood from neonates were drawn.Pertussis bacillus IgG antibody (PER-IgG) and pertussis toxin IgG antibody (PT-IgG) were tested using enzyme-linked immunosorbent assay. χ2 test was used to compare the positive rate of pertussis IgG antibodies in maternal and cord blood in the three hospitals. Correlational analyses of the antibodies levels in each hospital were conducted. The demographic characteristics, history of cough during pregnancy and history of DTaP vaccination of the mothers were collected via questionnaires. Result A total of 612 pairs of venous blood and cord blood samples were collected, including 4 mothers delivered twins and 616 cases of cord blood sample were collected. No history of pertussis were found in the 612 mothers. Among the 616 cases of umbilical cord blood, positive rate of PER-IgG was 13.3% (82/616), positive rate of PT-IgG was 0.5% (3/616). Among 612 cases of venous blood from the mothers, positive rate of PER-IgG was 7.7% (47/612), positive rate of PT-IgG was 0.3% (2/612). Positive rates of PER-IgG and PT-IgG in the mothers′ venous blood were not correlated with their residences (P=0.676 and 0.544). Positive rates of PER-IgG (r=0.842, P<0.001) and PT-IgG (r=0.619, P<0.001) in the mothers′ blood were positively correlated with the positive rate in umbilical cord blood. Conclusion This study shows that the positive rate of PER-IgG is very low in the maternal and umbilical cord blood in Beijing. Positive correlations of PER-IgG and PT-IgG between mother and umbilical cord blood were existed. Most mothers and their newborns do not have enough protection against pertussis.
9.cGAS enhances the HTLV-1 reverse transcription intermediate ssDNA90-induced innate immune re-sponses
Zhixiang GUO ; Di SONG ; Yue LIU ; Yuhan CUI ; Lingling MA ; Yuhe GUAN ; Bo YANG ; Jie WANG
Chinese Journal of Microbiology and Immunology 2018;38(6):434-439
Objective To investigate the role of cyclic GMP-AMP synthase (cGAS),a cytosolic DNA sensor,in regulating innate immune responses induced by reverse transcription intermediate of human T cell leukemia virus type 1 (HTLV-1). Methods (1)ssDNA90,the reverse transcription intermediate of HTLV-1,was transfected into HeLa cells to observe changes in the expression pattern of cGAS in transfected-HeLa cells with immunoblot assay. (2) HeLa cells were firstly transfected with cGAS-encoding plasmid and then ssDNA90 24 hours later. Real-time PCR was used to measure the expression of interferon ( IFN)-β, IFN-gamma-inducible protein 10 ( IP-10 ), regulated on activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-α. Immunoblot assay was performed to measure phosphorylated interferon regulatory factor 3 (IRF3) and p65. (3)cGAS expression was silenced by siRNA in HeLa and phorbol-12-myristate-13-acetate (PMA)-treated THP1 (PMA-THP1) cells and then ssDNA90 was transfect-ed into these cells 24 hours later. Real-time PCR was used to measure the expression of IFN-β,IP-10,RAN-TES and TNF-α. Immunoblot assay was performed to measure phosphorylated IRF3 and p65. Results Ex-pression of cGAS was increased in HeLa cells after ssDNA90 transfection. Compared with control cells, cGAS-transfected HeLa cells showed increased expression of IFN-β, IP-10, RANTES and TNF-α and en-hanced phosphorylation of IRF3 and p65 after ssDNA90 transfection. Compared with control cells,both HeLa and PMA-THP1 cells with silenced expression of cGAS showed impaired production of IFN-β,IP-10,RAN-TES and TNF-α after ssDNA90 transfection. Moreover,ssDNA90-induced phosphorylation of IRF3 and p65 were decreased after cGAS gene-knockdown. Conclusion cGAS might promote HTLV-1 RTI ssDNA90-in-duced innate immune responses.
10.Cyclic GMP-AMP synthase ( cGAS) inhibits the replication of human T cell leukemia virus type 1 (HTLV-1) in HeLa cells through regulating innate immune response
Lingling MA ; 453003 新乡医学院医学检验学院科研创新班 ; Zhixiang GUO ; Di SONG ; Yue LIU ; Yuhan CUI ; Yuhe GUAN ; Bo YANG ; Jie WANG
Chinese Journal of Microbiology and Immunology 2017;37(11):822-826
Objective To investigate the function and the possible mechanism of cyclic GMP-AMP synthase (cGAS), a DNA sensor, in HeLa cells during human T cell leukemia virus type 1 (HTLV-1) in-fection.Methods HeLa cells were co-cultured with MT2 cells (HTLV-1-positive T cells) and then detec-ted by immunoblot assay to analyze the changes in the expression of cGAS .A hemagglutinin ( HA)-tagged cGAS plasmid was constructed and transfected into HeLa cells .Twenty-four hours after transfection , these cells were co-cultured with MT2 cells for another 24 hours.Immunoblot assay was used to detect the expres-sion of HTLV-1 proteins Tax and p19.Real-time PCR was performed to measure the expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level .Immunoblot assay was also used to analyze the phosphorylation of interferon regulatory factor 3 (IRF3) and p65.Expression of interferon (IFN)-β, IFN-gamma-inducible protein 10 ( IP-10 ) , RANTES ( regulated on activation , normal T cell expressed and secreted ) and tumor necrosis factor (TNF)-αwas detected by real-time PCR assay.Results Expression of cGAS was enhanced in HeLa cells after co-cultured with MT2 cells.Compared with control cells , the HeLa cells that were trans-fected with cGAS plasmid showed lower levels of Tax and p 19 proteins, suppressed expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level , enhanced phosphorylation of IRF 3 and p65, and higher levels of IFN-β, IP-10, RANTES and TNF-αafter co-cultured with MT2 cells.Conclusion cGAS might promote the innate immune response and inhibit HTLV-1 replication in HTLV-1-infected HeLa cells .


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