1.MEG3 LncRNA from Exosomes Released from Cancer-Associated Fibroblasts Enhances Cisplatin Chemoresistance in SCLC via a MiR-15a-5p/CCNE1 Axis
Yulu SUN ; Guijun HAO ; Mengqi ZHUANG ; Huijuan LV ; Chunhong LIU ; Keli SU
Yonsei Medical Journal 2022;63(3):229-240
Purpose:
Long non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAs released from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This study aimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistance and cell processes in SCLC.
Materials and Methods:
Quantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, and CCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide and invasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progression in vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated by dual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explore the effects of exosomes on MEG3 expression in SCLC cell lines.
Results:
MEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis in SCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistance and cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis.
Conclusion
MEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.
2.Clinical characterization and genetic analysis of 5 Chinese families with glucokinase gene mutations
Yuansi CHEN ; Mingwei SHAO ; Gaofei REN ; Duo CHEN ; Feng GUO ; Yanxia LIU ; Zhizhen LI ; Liangge SUN ; Guijun QIN
Chinese Journal of Endocrinology and Metabolism 2022;38(8):645-650
Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.
3.The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65
Xichang WANG ; Haoyu WANG ; Li YAN ; Lihui YANG ; Yuanming XUE ; Jing YANG ; Yongli YAO ; Xulei TANG ; Nanwei TONG ; Guixia WANG ; Jinan ZHANG ; Youmin WANG ; Jianming BA ; Bing CHEN ; Jianling DU ; Lanjie HE ; Xiaoyang LAI ; Yanbo LI ; Zhaoli YAN ; Eryuan LIAO ; Chao LIU ; Libin LIU ; Guijun QIN ; Yingfen QIN ; Huibiao QUAN ; Bingyin SHI ; Hui SUN ; Zhen YE ; Qiao ZHANG ; Lihui ZHANG ; Jun ZHU ; Mei ZHU ; Yongze LI ; Weiping TENG ; Zhongyan SHAN
Endocrinology and Metabolism 2021;36(4):778-789
Background:
Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension.
Methods:
Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017.
Results:
The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years.
Conclusion
The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.
4.The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65
Xichang WANG ; Haoyu WANG ; Li YAN ; Lihui YANG ; Yuanming XUE ; Jing YANG ; Yongli YAO ; Xulei TANG ; Nanwei TONG ; Guixia WANG ; Jinan ZHANG ; Youmin WANG ; Jianming BA ; Bing CHEN ; Jianling DU ; Lanjie HE ; Xiaoyang LAI ; Yanbo LI ; Zhaoli YAN ; Eryuan LIAO ; Chao LIU ; Libin LIU ; Guijun QIN ; Yingfen QIN ; Huibiao QUAN ; Bingyin SHI ; Hui SUN ; Zhen YE ; Qiao ZHANG ; Lihui ZHANG ; Jun ZHU ; Mei ZHU ; Yongze LI ; Weiping TENG ; Zhongyan SHAN
Endocrinology and Metabolism 2021;36(4):778-789
Background:
Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension.
Methods:
Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017.
Results:
The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years.
Conclusion
The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.
5.Unqualified rate of anti-HIV detection in the laboratories from blood banks in Beijing-Tianjin-Hebei region
Wei ZHEN ; Hongwei GE ; Rui WANG ; Tong PAN ; Wei HAN ; Peng WANG ; Li YANG ; Shaoqiu SUN ; Xiao CAO ; Liye CUI ; Chao WEI ; Guijun YU ; Yunpeng XU ; Jinjuan FANG ; Caixia LIU ; Xuegang WANG ; Zhijun ZHEN ; Xiaojie LIU ; Wengong DU ; Lunan WANG ; Jiang LIU ; Hongjie WANG
Chinese Journal of Blood Transfusion 2021;34(4):371-376
【Objective】 To investigate the unqualified rate of anti-HIV detection of blood screening laboratories in Beijing-Tianjin-Hebei region, and explore the differences in anti-HIV detection ability and influencing factors in each laboratory. 【Methods】 Through filling questionnaires via e-mail, the anti-HIV ELISA unqualified rate and confirmed (WB) positive results (data) from January to December 2018 from 15 blood screening laboratories in Beijing-Tianjin-Hebei region were collected. Our laboratory was responsible for data collection and confirmation, and statistics software SPSS22.0 was used for analysis. 【Results】 1) There was a statistically significant difference among the unqualified rate of anti-HIV ELISA(6.77‱~35.71‱) and confirmed positive rate(0.60‱~3.56‱) in 15 blood screening laboratories in Beijing-Tianjin-Hebei region (P<0.05); 2) There were significant differencse among the ELISA unqualified rate and the confirmed positive rate of 8 reagents for anti-HIV detection(P<0.01), and the sensitivity of the 4th generation detection reagent and the imported reagent was higher than that of the 3rd generation reagent and the domestic reagent. The anti-HIV ELISA unqualified rate of R5 was the highest (19.08‱). 3)There were significant differences in the anti-HIV ELISA unqualified rate of R1, R2, R3, R5 and R7 reagents among different blood station laboratories(P<0.05), and there were no significant differences in the anti-HIV ELISA unqualified rate of R4, R6 and R8 reagents among different blood station laboratories(P>0.05). 4)The unqualified rate of anti-HIV ELISA of laboratories using different regents showed significant differences(P<0.05), except H, J, M. The unqualified rate of imported reagent was significantly higher than that of domestic reagents of laboratories using imported and domestic reagents combinations(P<0.05), except O. 62.5% (5/8) laboratories using domestic 3rd and 4th generation reagent combination showed significant differences in the unqualified rates among different reagents(P<0.05); 5) The positive rate of single-reagent(62.02%~95.45%)in 15 blood screening laboratories showed significant difference(P<0.001), and A was the lowest (62.02%). 【Conclusion】 The anti-HIV detection ability among 15 blood screening laboratories in Beijing-Tianjin-Hebei region is quite different. The application of different reagents is the main factor for the difference, and other factors such as personnel, instruments and test strategies also has a great impact on the detection of anti-HIV. It is still necessary to promote the process of homogenization of blood testing quality among blood screening laboratories in Beijing-Tianjin-Hebei region.
6.Relationship between abdominal fat distribution and diabetic complications in patients with type 2 diabetes mellitus
Huiqin XIONG ; Pengyu ZHANG ; Xialian LI ; Huijuan ZHANG ; Liguo YANG ; Yan WU ; Liangge SUN ; Guijun QIN
Chinese Journal of Endocrinology and Metabolism 2020;36(4):299-303
Objective:To investigate the association of abdominal fat distribution with glycolipid metabolism and diabetic complications in patients with T2DM.Methods:Totally 357 inpatients with T2DM were collected from the Endocrinology Department of our hospital. All patients received quantitative computed tomography to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and were divided into three groups depending on the tertile of VAT value: T1 group (VAT<162.0 cm 2), T2 group (162.0≤VAT<221.1 cm 2), T3 group (VAT≥221.1 cm 2). The incidences of diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy, peripheral atherosclerosis, and cardia-cerebrovascular disease were examined in all patients. Results:HbA 1C level in T1 group was higher than that in T3 group( P<0.05). High density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) in T1 group were higher compared with those in T2 and T3 groups ( P<0.05). Male proportion, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), 24h urinary albumin, diabetic kidney disease and peripheral atherosclerosis in T2 and T3 groups were higher than those in T1 group ( P<0.05). Fasting C- peptide (FCP) and modified homeostasis model assessment for insulin resistance (HOMA-IR) in T3 group were higher than those in T1 and T2 group ( P<0.01). VAT and SAT were positively correlated with BMI, FCP, and HOMA-IR (p<0.01). VAT was positively correlated with age, SBP, DBP, TG, 24h urinary albumin, diabetic kidney disease, peripheral atherosclerosis, and cardia-cerebrovascular disease ( P<0.05), while inversely correlated with HbA 1C, HDL-C, and eGFR ( P<0.05). SAT was positively correlated with total cholesterol and low density lipoprotein-cholesterol ( P<0.01), while negatively correlated with peripheral atherosclerosis ( P<0.01). Multivariate logistic regression analysis showed that VAT was still a risk factor for diabetic kidney disease after adjusted by age, BMI, SBP and fasting plasma glucose( P=0.013). Conclusion:VAT and SAT are associated with blood lipids and insulin resistance, while VAT seems to be a risk factor for diabetic kidney disease.
7.Differential diagnosis of nonclassical 21-hydroxylase deficiency and polycystic ovary syndrome
Shengnan WANG ; Yanjie XIA ; Lijun XU ; Qin YU ; Xialian LI ; Liangge SUN ; Guijun QIN ; Huijuan ZHANG
Chinese Journal of Endocrinology and Metabolism 2020;36(4):288-293
Objective:To explore the differential diagnosis methods between nonclassical 21-hydroxylase deficiency(NC21-OHD) and polycystic ovary syndrome(PCOS).Methods:The clinical data of 31 women with NC21-OHD were compared with those of 29 women with PCOS.Results:Women with NC21-OHD showed a higher prevalence of adrenal hyperplasia and lower likelihood of polycystic ovary(PCO) than those with PCOS( P<0.05), with lower height( P<0.05). The levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone(17-OHP), androstenedione(AD), total testosterone(TT), and progesterone were higher in women with NC21-OHD compared with those with PCOS( P<0.05). Women with PCOS had higher levels of luteinizing hormone(LH) and higher ratio of LH to follicle stimulating hormone(FSH) than those with NC21-OHD( P<0.05). The best two identification indexes for the two diseases were 17-OHP and progesterone, with the optimal cut-off points 3.34 ng/ml(sensitivity 89.7%, specificity 93.1%) and 0.64 ng/ml(sensitivity 90.0%, specificity 75.9%), respectively. During the 1-day mid-dose dexamethasone suppression test(DST), women with NC21-OHD had higher inhibition rates of 17-OHP, progesterone, AD, and TT( P<0.01) than those with PCOS. Their optimal cut-off values of suppression rates were 73.5%(sensitivity 95.2%, specificity 100.0%), 55.5%(sensitivity 100%, specificity 88.9%), 61.4%(sensitivity 84.2%, specificity 100.0%), 68.3%(sensitivity 65.0%, specificity 100.0%), respectively. Conclusion:The clinical manifestations of women with NC21-OHD are similar to those with PCOS. 17-OHP is the best differential indicator and the 1-day mid-dose DST plays an important role in the identification of the two diseases. Genetic analysis is the gold standard for distinguishing the two diseases.
8.Comparison of perioperative conditions between total and partial colpocleisis for elderly patients suffered from severe pelvic organ prolapse
Rui JU ; Xin YANG ; Xiuli SUN ; Xiaowei LI ; Guijun ZHAO ; Hongying WANG ; Jianliu WANG
Chinese Journal of Obstetrics and Gynecology 2019;54(1):33-37
Objective To study perioperative period conditions of total and partial colpocleisis with severe pelvic organ prolapse(POP)in elderly patients. Methods From Jan. 2014 to Oct. 2017286 severe POP elderly patients underwent total or partial colpocleisis. The mean age was(76.0±5.1)years(60-90 years). Of which,220 patients(76.9%, 220/286)presented more than one kind of medical disease. The operative time, intraoperative blood loss, hospital stay after surgery, postoperative complications, preoperative urinary dysuria symptoms of total and partial colpocleisis in treatment of 286 patients were analyzed. Results In 286 patients, 172 patients(60.1%)underwent total colpocleisis and 114 patients(39.9%) underwent partial colpocleisis. Totally 48 patients(16.8%)in 286 patients underwent anti-urinary incontinence procedure. The mean operating time of 286 patients was(67 ± 22)minutes, the mean blood loss was(52 ±57)ml, the mean hospital stay after surgery was(5.9 ± 1.9)days(2-16 days). The rate of postoperative complications was 8.7%(25/286). Those complications including 1 case of bladder injury during operation, 3 cases of postoperative pelvic hematoma, 1 case of intestinal obstruction, 5 cases of atrial fibrillation, 10 cases of postoperative morbidity, 3 cases of pulmonary embolism, 1 case of lower limb thrombosis, 1 case of urinary retention underwent electrical stimulation treatment because of ineffective application of urinary retention catheter. The mean operating time was(67±22)minutes in total colpocleisis and(68±20) minutes in partial colpocleisis(P>0.05), the mean blood loss was(58±62)ml in total colpocleisis and(41± 45)ml in partial colpocleisis(P>0.05), the mean hospital stay after surgery was(5.9 ± 1.9)days in total colpocleisis and(6.0 ± 1.8)days in partial colpocleisis(P>0.05), the rate of post operative complications was 8.1%(14/172) in total colpocleisis and 9.6%(11/114)in partial colpocleisis(P>0.05), respectively;those four of comparisons showed no significant difference. There were 129 patients(45.1%, 129/286)with voiding difficulty before surgery;the mean postvoid residual volumes of the above two operation types of people after operation were(35 ± 43)and(34 ± 41)ml, which showed no significant difference(P>0.05). Conclusions Colpocleisis is a safe and effective management in selected elderly patients with severe POP, who no longer desire to maintain vaginal coital function. There is no significant difference in the perioperative period conditions between total and partial colpocleisis. The choice of surgical procedure is based on factors such as the presence or absence of malignancy in the uterus, age and willingness of the patient, and general condition.
9. Study on six patients with 17α-hydroxylase/17, 20-lyase deficiency
Yameng LIU ; Yanjie XIA ; Xiaoying LI ; Xialian LI ; Qin YU ; Liangge SUN ; Guijun QIN ; Huijuan ZHANG
Chinese Journal of Endocrinology and Metabolism 2019;35(10):825-828
Objective:
To improve the understanding of 17α-hydroxylase/17, 20-lyase deficiency(17OHD)disease.
Methods:
The clinical data of six patients suffering from 17OHD were analyzed retrospectively.
Results:
Two patients with complete combined defect had typical clinical presentations, including absence of secondary sexual characteristics, primary amenorrhea, hypertension, hypokalamia, lower gonadal hormone levels, as well as elevated corticotropin and progesterone levels. TAC329AA homozygous mutation, IVS1+ 2T>C, and c. 775_776delAT complex heterozygous mutation were found in 2 cases. Four cases of partial combined defect showed high progesterone, lower gonadal hormones and dehydroepiandrosterone-sulfate levels. Three females(46, XX)showed spontaneous menstrual and primary infertility, and two of them got successful pregnancy with assisted reproductive technology. TAC329AA heterozygous mutation was found in those 4 cases.
Conclusions
TAC329AA mutation is common in 17OHD, and heterozygous or homozygous mutation of TAC329AA may be the genetic and molecular basis for determining whether these patients present as partial or complete defect. The elevated plasma progesterone in non-pregnancy combined with lower gonadal hormones and dehydroepiandrosterone-sulfate is the main character of patients with partial 17OHD. Less severe patients may be able to get successful pregnancy with assisted reproductive technology.
10.Self-management experience of patients with schizophrenia: a qualitative study
Yan WU ; Jingyi CUI ; Airong SUN ; Guijun MA
Chinese Journal of Modern Nursing 2019;25(23):2952-2956
Objective? To explore the process and experience of self-management among patients with schizophrenia by interview so as to provide examples and inspirations for clinical nursing and improving self-management among patients with schizophrenia. Methods? From February to April 2018, we collected information in 14 schizophrenia outpatients at a ClassⅢ Grade A psychiatric hospital in Beijing by semi-structured depth interview. The information was analyzed and summarized with the method of content analysis. Results? The interview results were divided into two aspects. On the one hand, the cognition of schizophrenia patients on self-management limited the self-management ability development of patients including lack of knowledge on self-management and family dysfunction. On the other hand, the experience of self-management also limited the ability involving lack of symptom management ability, skills and knowledge on treatment management, poor emotion management, low daily life management initiative, poor interpersonal management and inadequate social support resource use. Conclusions? Medical staff should actively understand the self-management of schizophrenia patients, strengthen training and education so as to improve disease self-management and promote recovery from disease.

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