2.Research advances in relationship between methyl-CpG binding domain proteins and the repression of tumor repressor genes
Lingling GUO ; Fengying DUAN ; Xiaohua QIU
Cancer Research and Clinic 2008;20(3):211-213
Many genetic events have been described to be involved in the development of tumor,but a lot of recent researches proved that epigenic events also played an important role in it.DNA methylation is one of the common modification of epigenic events,the binding of methyl-CpG binding domain proteins has been shown to lead to transcriptional repression of many tumor repressor genes.
3.Study on the expression and clinical significance of p53 and bcl-2 in different cutaneous tumors
Song ZHAO ; Huijun DUAN ; Fengying QI ; Yingmin LI
Cancer Research and Clinic 1997;0(03):-
Objective To explore the significance of the expression of p53 and bcl- 2 in different cutaneous tumors. Methods The expression of p53 and bcl- 2 were quantitatively detected by Flow Cytometry(FCM) and immunofluorescence in 10 cases of normal skin, 20 cases of squamous cell carcinoma(SCC), 22 cases of basal cell carcinoma(BCC), 18 cases of malignant melanoma(MM) and 18 cases of pigmented nevus (PN). Fluorescence Index(FI) was defined as the expression index of bcl- 2 and p53 protein. Results The FI for bcl- 2 in SCC and BCC was higher than that in normal skin tissues(P
4.Value of octreotide suppression test in predicting the efficacy of long-acting somatostatin receptor ligands in pituitary GH adenomas
Ran LI ; Lian DUAN ; Hui PAN ; Shengmin YANG ; Linjie WANG ; Hongbo YANG ; Fengying GONG ; Xiaoan KE ; Meiping CHEN ; Huijuan ZHU
Chinese Journal of Endocrinology and Metabolism 2022;38(4):288-293
Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.
6.Genotype-phenotype landscape of pituitary adrenocorticotroph hormone adenoma
Hui MIAO ; Luo WANG ; Fengying GONG ; Lian DUAN ; Linjie WANG ; Yong YAO ; Ming FENG ; Kan DENG ; Renzhi WANG ; Yanfang GUAN ; Huijuan ZHU ; Lin LU
Chinese Journal of Endocrinology and Metabolism 2022;38(2):125-131
Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.
7.Changes in platelet related parameters in obese patients after sleeve gastrectomy
Yining ZHEN ; Fengying GONG ; Huijuan ZHU ; Jianchun YU ; Weiming KANG ; Yuxing ZHAO ; Hongbo YANG ; Lian DUAN ; Hui PAN ; Linjie WANG
Chinese Journal of Internal Medicine 2021;60(11):993-996
To compare changes in platelet related parameters in obese patients before and after sleeve gastrectomy (SG), we retrospectively analyzed the clinical data of 31 obese patients who underwent SG in Peking Union Medical College Hospital from December 2012 to September 2020. Results showed that compared with those before surgery, platelet count (PLT) decreased significantly at 2-12 weeks of follow-up ( P=0.009), while platelet distribution width (PDW), mean platelet volume (MPV), and large platelet ratio (P-LCR) increased significantly at the same periods of follow-up after operation ( P<0.001). However, the levels of PDW, MPV, and P-LCR began to decrease at 16-55 weeks when compared with those at 2-12 weeks of follow-up ( P<0.01). PLT was positively correlated with white blood cells and neutrophils at 2-12 weeks of follow-up and positively correlated with high sensitivity C-reactive protein at 16-55 weeks of follow-up after operation ( P<0.05).
8.Effects of orlistat and metformin on metabolism and gonadal function in overweight or obese patients with polycystic ovary syndrome
Yuxing ZHAO ; Linjie WANG ; Fengying GONG ; Hui PAN ; Hui MIAO ; Lian DUAN ; Hongbo YANG ; Huijuan ZHU
Chinese Journal of Internal Medicine 2021;60(12):1165-1168
The aim of this study was to assess the effects of orlistat or metformin treatment on lipid and glucose metabolism, and gonadal function in obese/overweight women with polycystic ovary syndrome (PCOS). A total of 39 patients diagnosed with PCOS were randomly (digital table method) divided into orlistat treatment group (20 cases) and metformin treatment group (19 cases). Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months ( P<0.05). No significant differences could be viewed between orlistat and metformin treated subjects. Moreover, orlistat treatment significantly lowered the levels of low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) ( P<0.05), while there were no significant changes in above parameters with metformin treatment. The improvement of menstrual cycle was observed after 6-month treatment in both groups ( P<0.05). However, changes in polycystic ovarian morphology by ultrasound were only observed in orlistat treated group. In conclusion, orlistat is comparable with metformin in weight loss and improvement of insulin resistance and menstrual cycle, and is superior to metformin in improvement of lipid metabolism in overweight/obese PCOS patients.
9.Research advances in natural drug and food monomers in prevention and treatment of alcoholic liver injury
Jingrong YE ; Yan LIN ; Hanyi DUAN ; Xiaolan REN ; Xue YANG ; Fengying ZHANG
Journal of Clinical Hepatology 2023;39(10):2476-2484
A large number of data show that the prevalence rate of alcoholic liver injury (ALI) is increasing year by year, and it has become one of the main causes of death due to chronic liver diseases such as liver cancer and liver cirrhosis. Quitting drinking is the main method for the prevention of ALI in modern medicine, and the main treatment methods include Western medicine with antioxidant and anti-fibrotic effects and nutritional support. However, Western medicine tends to have an unsatisfactory treatment effect and can only alleviate initial symptoms, and severe ALI still requires surgical treatment. Studies have shown that the monomers extracted from natural drugs and foods have obvious preventive and therapeutic effects on ALI, with high safety and easy access. Therefore, this article systematically summarizes the main natural drug and food monomers used for the prevention and treatment of ALI and proposes the idea of the combination of drug and food for the prevention and treatment of ALI from the perspective of paying attention to the whole process of health, in order to explore more effective prevention, health care, and treatment methods and provide ideas for research on the prevention and control of ALI.
10.Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis.
Xia XU ; Haiwen LU ; Jianxiong LI ; Jielin DUAN ; Zhongwei WANG ; Jiawei YANG ; Shuyi GU ; Rongguang LUO ; Shuo LIANG ; Wei TANG ; Fengying ZHANG ; Jingqing HANG ; Juan GE ; Xin LIN ; Jieming QU ; Xinming JIA ; Jinfu XU
Chinese Medical Journal 2023;136(16):1949-1958
BACKGROUND:
Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.
METHODS:
A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.
RESULTS:
The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.
CONCLUSION
Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans
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Aspergillosis, Allergic Bronchopulmonary/complications*
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Aspergillus fumigatus/genetics*
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Asthma/genetics*
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Aspergillus
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Mutation/genetics*
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CARD Signaling Adaptor Proteins/genetics*