1.Long non-coding RNA PVT1 mediates bile acid-induced gastric intestinal metaplasia via a miR-34b-5p/HNF4α positive feedback loop.
Kexin LIN ; Nuo YAO ; Xingyu ZHAO ; Xiaodong QU ; Xuezhi LI ; Songbo LI ; Shiyue LUO ; Min CHEN ; Na WANG ; Yongquan SHI
Chinese Medical Journal 2025;138(18):2324-2335
BACKGROUND:
Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment.
METHODS:
We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues.
RESULTS:
We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues.
CONCLUSIONS
BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans
;
RNA, Long Noncoding/metabolism*
;
MicroRNAs/metabolism*
;
Hepatocyte Nuclear Factor 4/genetics*
;
Bile Acids and Salts
;
Kruppel-Like Factor 4
;
Metaplasia/metabolism*
2.A sampling survey of intraoperative facial nerve monitoring in China
Yang ZHAO ; Songbo XUE ; Xu TIAN ; Guodong FENG ; Zhiqiang GAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(2):122-126
Objective:This study aims to investigate the current application and the level of knowledge of intraoperative facial nerve monitoring among medical staff in China.Methods:A comprehensive online questionnaire was conducted among medical professionals across different regions in China from October 2022 to February 2023. The survey exclusively targeted departments specializing in otolaryngology, head and neck surgery, neurosurgery, and oral and maxillofacial surgery. The questionnaire covered various aspects including general information, intraoperative facial nerve monitoring practices, training history, indications for monitoring, parameters used during monitoring procedures, as well as factors influencing its implementation.Results:A total of 417 participants from 31 provincial, municipal, and autonomous regions were included. Intraoperative facial nerve monitoring was found to be implemented in 227 (54.4%,227/417) repondents of 53 institutions (24.9%, 53/213). The top three indications for implementing this technique were acoustic neuroma, parotid gland surgery, and modified middle ear surgery (mastoidectomy). Herein 81.1%(184/227) medical staff involved in intraoperative facial nerve monitoring had received relevant training, 57.3%(130/227)-92.1%(209/227) reported a lack of clear description regarding recording thresholds, stimulation currents/frequencies/wave widths.Conclusion:The majority of the institutions surveyed have not yet adopted intraoperative facial nerve monitoring. Furthermore, significant gaps concerning the procedure exist. It is imperative to establish standards or guidelines to promote its better development and application.
4.Influencing factors of adult thyroid volume in Lanzhou City
Huixin TAO ; Songbo FU ; Xulei TANG ; Jingfang LIU ; Chengxu MA ; Gaojing JING ; Nan ZHAO ; Lihua MA ; Weiming SUN ; Ying NIU ; Qianglong NIU ; Juntao RAN ; Weiping TENG ; Zhongyan SHAN
Chinese Journal of Endemiology 2022;41(1):39-43
Objective:To investigate the thyroid volume of adults in Lanzhou City, and analyze its influencing factors.Methods:In June 2016, according to the principle of multi-stage stratified cluster sampling, Han residents aged 18 and above in Chengguan, Xigu and Qilihe districts of Lanzhou City who had lived there for more than 5 years were selected as research subjects, and a portable B-ultrasound machine was used for thyroid examination. Morning urine samples of the subjects were collected to test urinary iodine; fasting venous blood samples of the subjects were collected to test serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb), blood lipids [triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL)] and blood uric acid (Ua) levels. At the same time, body indexes systolic blood pressure (SP), diastolic blood pressure (DP), waist circumference, height and weight were measured, and the body mass index (BMI) was calculated. Multiple linear regression was used to analyze the influencing factors of thyroid volume.Results:A total of 1 009 subjects were included, aged (43.50 ± 15.16) years, and the thyroid volume was (8.74 ± 3.39) ml. Among them, 534 males had a thyroid volume of (9.46 ± 3.43) ml; 475 females had a thyroid volume of (7.93 ± 3.15) ml, the thyroid volume of males was larger than that of females ( t = 7.36, P < 0.01). Thyroid volume was positively correlated with age, height, weight, BMI, SP, waist circumference, LDL, Ua and TgAb ( r = 0.07, 0.23, 0.33, 0.27, 0.10, 0.27, 0.10, 0.08, 0.07, P < 0.05), and it was negatively correlated with thyroid nodules, TPOAb, TSH and urinary iodine ( r = - 0.16, - 0.07, - 0.10, - 0.08, P < 0.05). After multiple linear regression analysis, TSH, TPOAb, TgAb and thyroid nodules were included in the regression equation, and the standardized B values were - 0.135, - 0.065, 0.123 and - 0.197, respectively. Conclusions:The thyroid volume of males is larger than that of females in Lanzhou City. TSH, TPOAb, TgAb and thyroid nodules are influencing factors of thyroid volume.
5.High-quality Arabidopsis thaliana Genome Assembly with Nanopore and HiFi Long Reads
Wang BO ; Yang XIAOFEI ; Jia YANYAN ; Xu YU ; Jia PENG ; Dang NINGXIN ; Wang SONGBO ; Xu TUN ; Zhao XIXI ; Gao SHENGHAN ; Dong QUANBIN ; Ye KAI
Genomics, Proteomics & Bioinformatics 2022;20(1):4-13
Arabidopsis thaliana is an important and long-established model species for plant molec-ular biology,genetics,epigenetics,and genomics.However,the latest version of reference genome still contains a significant number of missing segments.Here,we reported a high-quality and almost complete Col-0 genome assembly with two gaps(named Col-XJTU)by combining the Oxford Nanopore Technologies ultra-long reads,Pacific Biosciences high-fidelity long reads,and Hi-C data.The total genome assembly size is 133,725,193 bp,introducing 14.6 Mb of novel sequences compared to the TAIR1 0.1 reference genome.All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality(QV)scores>60(ranging from 62 to 68),which are higher than those of the TAIR10.1 reference(ranging from 45 to 52).We completely resolved chro-mosome(Chr)3 and Chr5 in a telomere-to-telomere manner.Chr4 was completely resolved except the nucleolar organizing regions,which comprise long repetitive DNA fragments.The Chr1 cen-tromere(CEN1),reportedly around 9 Mb in length,is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats.Using the cutting-edge sequencing data and novel computational approaches,we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2.We also investigated the structure and epigenetics of centromeres.Four clusters of CEN180 monomers were detected,and the centromere-specific histone H3-like protein(CENH3)exhibited a strong preference for CEN 180 Cluster 3.Moreover,we observed hypomethylation patterns in CENH3-enriched regions.We believe that this high-quality genome assembly,Col-XJTU,would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms,as well as the genetic and epigenetic features in plants.
6.Detection of thyroid nodules in people with abnormal lipid metabolism and related factors
Xingyu CHANG ; Songbo FU ; Xulei TANG ; Jingfang LIU ; Nan ZHAO ; Gaojing JING ; Qianglong NIU ; Lihua MA ; Yinlong CHANG ; Junqin MOU ; Weiping TENG ; Zhongyan SHAN
Chinese Journal of Endemiology 2021;40(9):718-723
Objective:To investigate the detection rate and related factors of thyroid nodules in people with abnormal lipid metabolism.Methods:From September 4, 2016 to February 1, 2017, community residents living in Lanzhou City, Longnan City, Dingxi City and Linxia City of Gansu Province for more than 5 years were selected as the respondents. General data were recorded, venous blood was collected, blood lipid related biochemical indexes were detected, and thyroid ultrasound was performed. By comparing the general data and biochemical indexes, the detection of abnormal lipid metabolism and thyroid nodules were analyzed, and the risk factors of thyroid nodules in people with abnormal lipid metabolism were analyzed by logistic regression.Results:Two thousand and fifty-nine residents were included in this study (1 049 males and 1 010 females). The total detection rate of thyroid nodules was 23.17% (477/2 059). The detection rate of thyroid nodules in people with abnormal lipid metabolism [34.16%(151/442)] was significantly higher than that in people with normal lipid metabolism [20.16% (326/1 617) , P < 0.01], and the detection rate of thyroid nodules of women [43.37% (85/196) ] was higher than that of men [26.83% (66/246) , P < 0.01]. Among the people with abnormal lipid metabolism, the highest detection rate of thyroid nodules was in mixed hyperlipidemia [57.14% (16/28)], followed by hypertriglyceridemia [34.59% (92/266)]. The detection rates of thyroid nodules in the groups with elevated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels [35.16% (32/91), 34.85% (23/66)] were higher than those in the marginal elevated group [27.04%(86/318), 30.42% (73/240)] and the normal groups [21.76% (359/1 650), 21.73% (381/1 753), P < 0.05]. The results of logistic regression analysis showed that the risk factors of thyroid nodules in people with abnormal lipid metabolism were increased age, elevated fasting blood glucose (FPG), elevated blood glucose 2 hours (2 h PG) after oral glucose tolerance test (OGTT) load and elevated glycosylated hemoglobin [HbA1c, odds ratio ( OR)=1.065, 1.387, 1.866, 1.384, P < 0.05]. Conclusions:The prevalence of TN is higher in populations with abnormal lipid metabolism. The control of blood sugar and blood lipid levels may play a role in the prevention of thyroid nodules.
7.Correlation of type 2 diabetes and impaired glucose regulation with chronic kidney disease in middle-aged and elderly individuals.
Qiangmei WANG ; Jieyu ZHEN ; Conghui GUAN ; Nan ZHAO ; Jinjin LIU ; Hongli LI ; Songbo FU ; Xulei TANG ; Yanping HAN ; Shan SU ; Di ZHANG ; Lijuan LIU ; Donghu ZHEN
Journal of Southern Medical University 2020;40(10):1457-1464
OBJECTIVE:
To explore the correlation of different glucose metabolism statues with chronic kidney disease (CKD) in middle-aged and elderly individuals in Lanzhou.
METHODS:
Based on the baseline data of REACTION Study in Lanzhou area, we randomly sampled 10 038 residents aged 40-75 years in 3 communities in Lanzhou, who were classified into normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes groups. The estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) were used to assess the renal function and albuminuria, respectively. Binary logistic regression was performed to analyze the contribution of the risk factors to CKD. Polynominal regression was used to determine the trends of eGFR with the increment of ACR.
RESULTS:
Among all the participants, the prevalences of albuminuria, CKD and renal insufficiency (RI) were 26.2%, 27.4% and 2.5%, respectively. The prevalence of albuminuria, CKD and RI were significantly higher in the diabetes group than in IGR and NGT groups (
CONCLUSIONS
Diabetes mellitus is a significant risk factor for albuminuria and RI, while IGR is not. Screening for albuminuria and eGFR is highly recommended for individuals with diabetes, hypertension, and obesity, especially in women and the elderly population.
Adult
;
Aged
;
Albuminuria/epidemiology*
;
Diabetes Mellitus, Type 2/epidemiology*
;
Female
;
Glomerular Filtration Rate
;
Glucose
;
Humans
;
Middle Aged
;
Prevalence
;
Renal Insufficiency, Chronic/epidemiology*
;
Risk Factors
8. A study on urinary iodine levels and influencing factors of urban and rural residents in some areas of Gansu Province
Jie GAO ; Jingfang LIU ; Xulei TANG ; Songbo FU ; Lihua MA ; Caihong JIAO ; Weiming SUN ; Ying NIU ; Gaojing JING ; Qianglong NIU ; Nan ZHAO ; Yujuan LI ; Dan WU ; Pei SONG ; Huiping GUO ; Fang YANG ; Weiping TENG ; Zhongyan SHAN
Chinese Journal of Endemiology 2019;38(11):898-902
Objective:
To analyze the urinary iodine status of urban and rural residents in some areas of Gansu Province and its related influencing factors, and to provide certain references for scientific iodine intake of urban and rural residents in Gansu Province.
Methods:
Subjects in Gansu Province with normal thyroid function were recruited in the investigation of thyroid diseases and iodine nutritional status, conducted a questionnaire survey and measured height, weight, waist circumference, collected 1 urine sample, and tested their urinary iodine levels. The urinary iodine levels of different groups were compared based on different gender, region, age, body weight, the waist, and salt intaking. The affecting factors of urinary iodine levels were analyzed by multiple linear regression models.
Results:
Totally 1 964 subjects were recruited, including 1 099 males, and 865 females. The age was (41.23 ± 14.75) years old. The median urinary iodine of the selected group was 225.60 (158.80, 311.58) μg/L. The urinary iodine level of rural residents was significantly higher than that of urban residents [μg/L: 249.80 (180.58, 336.88)
9.Clinical spectrum, treatment and outcomes of uveal melanoma in a tertiary centre.
Wendy WONG ; Gangadhara SUNDAR ; Caroline CHEE ; Paul Songbo ZHAO ; Rajesh RAJAGOPALAN ; Lingam GOPAL
Singapore medical journal 2019;60(9):474-478
INTRODUCTION:
We aimed to describe the clinical characteristics, diagnostic challenges, treatment patterns and outcomes of uveal melanoma (UM) in a tertiary care centre.
METHODS:
This is a retrospective case series of 11 consecutive patients with UM who were managed in a tertiary referral centre between 2002 and 2017. Epidemiological, clinical, pathological and radiological characteristics were reviewed. Classification of choroidal melanoma as small, medium or large was based on the criteria established by the Collaborative Ocular Melanoma Study.
RESULTS:
Mean age at presentation was 42.9 (range 27‒67) years. In 7 (64%) patients, a definitive diagnosis of UM was made after a mean follow-up period of 6.4 (range 1‒17) months. There were one, six and four patients with small-, medium- and large-sized choroidal melanomas, respectively. Treatment was enucleation in 5 (45.5%) patients, plaque brachytherapy in 4 (36.4%) patients, transpupillary thermotherapy in 1 (9.1%) patient, and observation in 1 (9.1%) patient. Median follow-up was 29 months. Metastatic disease developed in 5 (45.5%) patients at the mean age of 46.6 (range 38‒56) years, with median overall survival of 20 months. Genetic mutations in three patients were monosomy 3 (n = 2), and gain of 3q and 8q (n = 1).
CONCLUSION
Our study supports the finding that UM in Chinese and Asian Indian patients presents at a younger age than in Caucasians. Although it is rare, ophthalmologists should remain mindful of this life-threatening disease. We propose establishing a national and regional registry for ocular tumours with genetic information to characterise the disease spectrum in Southeast Asia.
10.CAR-NK-92MI and CAR-CD19-T cells targeting CD19 antigen exhibit significant in vitro killing activity on mantle cell lymphoma
ZHAO Songbo ; HAN Zhichao ; AN Gangli ; MENG Huimin ; YANG Lin
Chinese Journal of Cancer Biotherapy 2018;25(5):455-461
[Abstract] Objective: To investigate the in vitro cytotoxicity of the chimeric antigen receptor-modified T cells and NK-92MI cells (CAR-NK-92MI cells) and CAR-CD19-T cells against mantle cell lymphoma (MCL). Methods: CAR-T cell technology, successfully obtained in clinical trial of B-lineage acute lymphoblastic leukemia (B-ALL) treatment, was used in this study. In the case of high expression of CD19 antigen in MCL, CAR- CD19-T cells and CAR- CD19-NK-92MI cells targeting CD19 antigen were generated, respectively. Then, their cytotoxicity against MCL cell lines was detected by LDH release assay and the results were verified by flow cytometry. Results: Compared with control group, both CAR-NK-92MI and CAR-CD19-T cells exhibited prominent killing effect against MCLcells(all P<0.01); in addition, the two CAR cells exhibited high cytotoxicity against K562-CD19 cells but not on K562 cells(all P <0.01). The death rate of MCL cells from CAR-NK-92MI group was 30%-40% more than that of control group, and the death rate of MCL from CAR-CD19-T group was 40%-50% more than that of control group. Conclusion: Both CAR-NK-92MI and CAR-CD19-T cells exhibited potent cytotoxicity against MCLcells in vitro.

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