1.The functional role of long non-coding RNA PANDAR in promoting colorectal cancer metastasis and its mechanism
Ning LIU ; Dongdong CHENG ; Jinbo JIANG
China Oncology 2017;27(4):268-275
Background and purpose: Accumulating evidence has revealed that long non-coding RNA (lncRNA) is correlated with carcinogenesis and tumor development. Recent literature suggested that lncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) was involved in the development of various cancers. However, the functional role of PANDAR in colorectal cancer (CRC) has not been elucidated yet. The present study aimed to explore the functional role of lncRNA PANDAR in promoting CRC metastasis and its mechanism.Methods: The expression of lncRNA PANDAR in CRC cell lines and tissues was detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR), and the correlation between lncRNA PANDAR expression and CRC clinicopathological characteristics was statistically analyzed. Then, lncRNA PANDAR stably silencing CRC cells (HCT116-shPANDAR), overexpression cells (DLD1-PANDAR) and control vector cells (HCT116-shNC and DLD1-vector) were established using lentiviral vectors. Moreover, Transwell assay and Matrigel assay were performed to investigate the function of lncRNA PANDAR in CRC migration and invasion. Furthermore, the expression of transcriptional factors mediating epithelial-mesenchymal transition of lncRNA PANDAR overexpression cells were monitored by RTFQ-PCR assay, and the function of the target gene in modulating lncRNA PANDAR mediated CRC metastasis was also explored. Results: The expression levels of lncRNA PANDAR in normal colorectal epithelial cells were much lower than in CRC cell. The levels of lncRNA PANDAR in tumor-adjacent tissues were verified to be much lower than in CRC tissues [(171.52±97.80)% vs (100.00±63.18)%, P<0.05]. Moreover, the expression of lncRNA PANDAR was detected to be significantly correlated with CRC TNM stage, lymph node metastasis and distant metastasis (P<0.05). Besides, lncRNA PANDAR deficiency significantly reduced the migration [100.00% vs (42.08±4.77)%, P<0.05] and invasion [100.00% vs (39.14±3.81)%, P<0.05] capabilities in CRC cells, in contrast, the migration [100.00% vs (194.12±9.33)%, P<0.05] and invasion [100.00% vs (204.08±12.27)%, P<0.05] capa-bilities of CRC cells were obviously increased with lncRNA PANDAR overexpression. Furthermore, zinc-finger E-box binding homeobox 1 (ZEB1) expression was detected to be positively correlated with lncRNA PANDAR expression, and ZEB1 silencing could significantly reverse the increased migration and invasion capabilities induced by lncRNA PANDAR in CRC cells. Conclusion: LncRNA PANDAR could promote CRC metastasis by potentially targeting ZEB1. LncRNA PANDAR might be a promising diagnostic marker and therapeutic target for CRC patients.
2.Research about the tolerance of GK rats in stress hyperglycemia associated with acute sepsis
Dongdong JIANG ; Tingting HAN ; Yao ZHANG ; Yangxue LI ; Yaomin HU
Chinese Journal of Endocrinology and Metabolism 2014;30(5):422-427
Objective To compare the differences in responsive ability and oxidative stress damage between type 2 diabetic rats and normal rats under acute sepsis associated with stress hyperglycemia.Methods GK rats with type 2 diabetes and Wistar rats were established critical ill models of sepsis by intraperitoneal injection of 5 mg/kg lipopolysaccharide(LPS).Before and after LPS injection,serum levels of proinflammatory cytokines tumor necrosis factor α (TNF-α),interleukin (IL)-1β3,and IL-6,and anti-inflammatory cytokine IL-10 were determined.Malondialdehyde (MDA) and total antioxidative capacity (T-AOC) levels in serum and tissues (lung,liver,kidney,heart) were measured by colorimetric determination.Results Before LPS injection,serum levels of TNF-α,IL-6,and IL-10 in GK rats were higher than those of Wistar rats.The serum levels of TNF-α,IL-6,and IL-10 after LPS injection were raised in both GK rats and Wistar rats (all P<0.05).At baseline,serum MDA level of GK rats was higher than that of Wistar group [(25.76 vs 12.71) μmol/L,P<0.05],while T-AOC level were lower [(0.60 vs 2.8) U/ml,P<0.05].One hour after LPS injection,the serum MDA level in two kinds of rats significantly increased compared with those of their baseline levels [(32.30 and 20.19) μmol/L,both P<0.05],while their serum T-AOC level decreased [(0.20 and 2.08) U/ml,P<0.05]).There were no signigicant differences in the change trend of serum MDA and T-AOC between the two kinds of rats.MDA and T-AOC levels in tissues had no significant difference before and after LPS injection in GK and Wistar rats (P>0.05).Conclusions The rats with type 2 diabetes had lowered level of proinflammatory factors and raised level of anti-inflammatory factors under acute sepsis,presenting better tolerance and lowered probability of inflammatory diffusion compared with normal rats.
3.The effects of newborn genetic screening for GJB2 and hearing follow-ups.
Ruzhen GAO ; Xiaowei CHEN ; Dongdong LI ; Hong JIANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(4):314-318
OBJECTIVE:
To determine the prevalence of GJB2 mutations in newborns and provide clinical experience for newborn genetic screening.
METHOD:
Blood samples of 23 836 newborns in Beijing from March 2012 to December 2013 were screened for hot spot mutations of GJB2 associated with hearing loss. The genetic screening results were comprehensively analyzed with hearing results in genetic counseling.
RESULT:
One or two pathogenic mutations of GJB2 were spotted in 622(2. 61%) individuals. Among them, numbers of newborns with 1 mutation of c. 35deiG,c. 176191 del16,c. 235delC and c. 299300 delAT were 3,26,467 and 120. One compound heterozygote, and 5 homozygotes were also identified. Five hundred and fifty(88. 6%)newborns were followed up by telephones and SMS (short message service) and 325 newborns visit our genetic clinic regularly which were regarded as the research object. In the hearing screening, the referral rate for hearing loss in the first-step screening was 13.8% (45/325), and became 9.2% (30/325) upon retesting. Nine newborns (2. 8%) were diagnosed as hearing loss of different degrees as early as 3 months old,including 6 homozygous/compound heterozygote and 3 heterozygotes.
CONCLUSION
Patients with GJB2 mutations have various phenotype. Newborns with homozygous/compound heterozygous GJB2 mutations may pass the hearing screening at first. Carriers of GJB2 may also have hearing problems. The combination of genetic and audiological screening can play an important role in deafness detections of infants before key period of speech development.
Base Sequence
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Connexin 26
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Connexins
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genetics
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Deafness
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genetics
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Follow-Up Studies
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Genetic Testing
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Hearing Loss
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genetics
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Hearing Tests
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Heterozygote
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Humans
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Infant
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Infant, Newborn
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Mutation
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Neonatal Screening
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Prevalence
4.Application of subtalar joint distractor in operative treatment for comminuted calcaneal fracture
Donghao XU ; Maozhong HU ; Dongdong WAN ; Wenxue JIANG ; Aimin YAO
Chinese Journal of Trauma 2016;32(3):218-222
Objective To evaluate the method and clinical effect of subtalar joint distractor assisted open reduction and internal fixation of comminuted intra-articular calcaneal fracture.Methods Twenty-two patients with fresh closed calcaneal fracture treated with open reduction and internal fixation from May 2011 to July 2013 were included in the study.According to the modes of operation,the patients were randomly divided into two groups (n =11 in each):in group A patients underwent fracture reduction assisted by subtalar joint distractor and in group B patients underwent Steinmann pin traction and poking reduction.All were fixed using the lateral calcaneal plate.Operation time,B(o)hler angle,Gissanes angle,calcaneus height,incision healing time and complications of the two groups were investigated for evaluating the effect of operation.Clinical effect was evaluated using the American Orthopedic Foot & Ankle Society (AOFAS) score before the removal of internal fixation.Results Period of follow-up was (14.3±0.8)months (range,12 to 18 months).Two patients in group B had delayed wound healing,and were treated with regular wound care.At the final follow-up,no infection,nonunion,malunion and internal fixation failure were observed.B(o)hler angle,operation time and calcaneus height observed in group A were superior to those in group B (P <0.01).There was no significant difference in Gissanes angle between the two groups (P > 0.05).Compared to the preoperative data,B(o)hler angle,Gissanes angle and calcaneus height were significantly improved in both groups (P <0.01).AOFAS score was (83.6 ± 1.4) points in group A and (81.7 ± 1.5) points in group B.Conclusion Subtalar joint distractor assisted open reduction and internal fixation is effective to shorten operation time,improve fracture reduction,reduce wound complications and increase the operative effect for comminuted intraarticular calcaneal fracture.
5.Factors affecting the risk of non-proliferative diabetic retinopathy among patients with type 2 diabetic mellitus
Jiajia JIANG ; Feng LI ; Dongdong FANG ; Wenjun YOU ; Weiwei WANG
Journal of Preventive Medicine 2023;35(1):17-20
Objective:
To investigate the factors affecting the development of non-proliferative diabetic retinopathy (NPDR) among patients with type 2 diabetic mellitus (T2DM), so as to provide insights into manangement of NPDR.
Methods:
T2DM patients without obvious eye discomfort at ages of 18 years and older admitted to Department of Endocrinology, Jining No. 1 People's Hospital during the period from December 2019 to May 2021 were enrolled. Participants' demographics, smoking, alcohol consumption, medical history of diabetes and use of medicines were collected, and the height, weight and blood pressure were measured. The levels of glycosylated hemoglobin (HbA1c), fasting blood glucose, blood C-peptide, lipid and creatinine were tested, and retinopathy was examined with a non-mydriatic fundus camera. The factors affecting the development of NPDR were identified among T2DM patients using a multivariable logistic regression model.
Results:
A total of 486 T2DM patients were enrolled, including 354 men (72.84%), with a median age of 48.00 (15.25) years, and median diabetes duration of 35.00 (104.25) months. The prevalence of NPDR was 19.34% among the participants. multivariable logistic regression analysis identified an educational level of senior high school and above (OR=0.546, 95%CI: 0.325-0.918), duration of diabetes (OR=1.008, 95%CI: 1.005-1.012), HbA1c (OR=1.183, 95%CI: 1.034-1.354) and use of non-sulfonylurea insulin secretagogues (OR=1.859, 95%CI: 1.082-3.196) as factors affecting the risk of NPDR among T2DM patients.
Conclusion
A high risk of NPDR is found among T2DM patients with a low educational level, long duration of diabetes, poor HbA1c control and use of non-sulfonylurea insulin secretagogues.
6.Expression and Significance of ATP-Binding Cassette Proteins in Hepatocellular Carcinoma
Shuna YU ; Jiying JIANG ; Shifu ZHAO ; Dequan WEI ; Jie DI ; Baosong WANG ; Dongdong JIANG
Chinese Journal of Clinical Oncology 2010;37(4):190-193
Objective: To investigate the expression of ATP-Binding Cassette Proteins including P-gp (P-glycoprotein), MRP1 (multidrug resistance associated protein 1) and BCRP (breast cancer resistance protein) in hepatocellular carcinoma and its relationship with pathological features. Methods: The expression of P-gp/MDR1 (multidrug resistance gene 1), MRP1 and BCRP in hepatocellular carcinoma was examined by RT-PCR and immunohistochemistry in 34 cases of hepatocellular carcinoma and 19 cases of paraneoplastic hepatic tissues. Results: The expression of MDR1, MRP1 and BCRP mRNA (messenger ribonucleic acid) was 1.15±0.24, 0.64±0.33, and 1.07±0.32 in hepatocellular carcinoma and 0.36±0.14, 0.19±0.06, and 0.31±0.09 in paraneoplastic hepatic tissues. The expression of MDR1, MRP1 and BCRP mRNA was 1.38±0.26, 0.73±0.35, and 1.34±0.21 in poorly differentiated hepatocellular carcinoma and 0.74±0.32, 0.30±0.11, and 0.45±0.13 in well differentiated hepatic tissues. The immunohistochemical positive substance was detected in the plasma membrane and cytoplasm. The positive rates of P-gp, MRP1 and BCRP were 82.35%, 58.82%, and 79.41% in hepatocellular carcinoma and 42.11%, 26.32%, and 36.84% in paraneoplastic hepatic tissues, respectively. The positive rates of P-gp, MRP1 and BCRP were 100.00%, 81.25%, and 100.00% in poorly differentiated hepatocellular carcinoma and 66.67%, 38.89%, and 61.11% in well differentiated hepatic tissues. The expression of three indicies in hepatocellular carcinoma was higher than that in paraneoplastic hepatic tissues (P<0.05). The expression of P-gp/MDR1, MRP1 and BCRP in poorly differentiated hepatocellular carcinoma was higher than that in well differentiated hepatic tissues (P<0.05). No correlation was found among the three indices. Conclusion: Intrinsic multidrug resistance exsists in hepatocellular carcinoma, with various mechanisms. The multidrug resistance of HCC (hepatic cell carcinoma) is related to P-gp/MDR1, MRP1 and BCRP. MRP1 and BCRP may be targets for reversing multidrug resistance.
7.Fetal rat liver filtrate induces the differentiation of rat bone marrow-derived mesenchymal stem cells into hepatocytes
Xiaocui WANG ; Jiying JIANG ; Jinsheng WU ; Jie DIN ; Shuna YU ; Dequan WEI ; Baosong WANG ; Dongdong JIANG
Acta Anatomica Sinica 2009;40(6):923-927
Objective To explore the possibility that rat bone mesenchymal cells (BMSCs) can differentiate into hepatocytes under the affection of fetal liver filtrate. Methods PAS and green indigo dye were used to detect glycogen and differential level of hepatocytes, respectively. The concentration of ALT, AST, ALP in the culture supernatant were served as markers of hepaocyte function. Results Fourteen days after induced by the fetal liver filtrate, BMSCs changed their shapes into polygon, oval or round. Some of BMSCs were positive for AFP and ALB at 7 days after induction, then the number of positive cells increased, and most of BMSCs expressed AFP and ALB till 21days. The PAS reaction and indocyanine green(ICG) intaking also appeared at 7days. Enzyme in supernatant such as ALT, AST, ALP were fristly detected at 7days and peaked at 14days,then the level declined. Conclusion The fetal rat liver filtrate was able to induce BMSCs into cells with function and characteristics of hepatocytes.
8.Treatment of acute cerebral thrombosis with a novel mutated tissue plasminogen activator
Jing BAI ; Linbai YE ; Hong JIANG ; Ying LIU ; Dongdong ZHAO ; Xinhong YANG ; Kui CHEN ; Bin SUN
Chinese Journal of Emergency Medicine 2010;19(7):717-721
Objective To evaluate the efficacy and safety of a novel mutated recombinant tissue-type plas-minogen activator (rt-Pam) in a rat model of acute cerebral thrombosis. Method Eighty-seven adult Wister rats were randomly divided into control group, recombinant tissue-type plasminogen activator (rt-PA) group, low dose of rt-Pam group and routine dose of rt-Pam group. The rats of different groups were treated for 3 hours after thrombosis of middle cerebral artery. The size of infarction, neurological scores and severity of hemorrhage were observed 24 hours after treatment. The protective role of rt-Pam in the brain tissue was evaluated as per the infiltration of neutrophils and the concentration of plasminogen activator receptor-1 (PAR-1). Results Compared with control group, the sizes of infarction in the low dose of rt-Pam group and routine dose of rt-Pam group were significantly smaller [(108.5 ±27.3) mm3 and (68.3 ±17.2) mm3 vs. (323.4 ±42.3) mm3]. The neurological scores were evidently correlated with the size of infarction (r = 0.613, P<0.001), while the liability of cerebral hemorrhage in low dose of rt-Pam group was not significantly increased. The rt-Pam also reduced the production of myeloperox-idase, as well as the production of PAR-1 in comparison with rt-PA group [(13.8 ± 3.1) vs. (28.3±4.5), P <0.00l]. Conclusions The novel rt-Pam could be a better thrombolytic agent than rt-PA in treating acute stroke.
9.Value of multi-detector CT low tension dynamic enhanced scanning in preoperative evaluation of advanced gastric cancer
Weijian GUO ; Pengcheng JIANG ; Dongdong DU ; Jian JING ; Xuebin WANG ; Yanqing YANG
Cancer Research and Clinic 2014;26(4):257-259,265
Objective To investigate the value of muhi-detector CT (MDCT) low tension dynamic enhanced scanning on the preoperative assessment of advanced gastric cancer.Methods MDCT low tension dynamic enhanced scanning,tumor diagnosis and staging and prediction of surgery operation were performed on 43 cases of advanced gastric cancer.And the above results were compared with pathology results.Results The 36 cases were treated with resection,while 7 cases were treated by gastrointestinal anastomosis.The MDCT had 76.7 % (33/43) of accuracy for the preoperative T staging and 74.4 % (32/43) of accuracy for the preoperative N staging,respectively.The stomach wall thickness was closely related to serosal invasion (x2 =20.170 9,P < 0.001).Conclusions The MDCT low tension dynamic enhanced scanning can improve the comprehensiveness and accuracy of preoperative staging of T and N in advanced gastric cancer.It is valuable for the preoperative diagnosis and treatment of gastric cancer.
10.Clinical outcomes and safety of percutaneous coronary intervention only in single-opened vessel lesion among patients with severe left ventricular systolic dysfunction
Dongju JIANG ; Rong FU ; Gaopin HU ; Yulin JIA ; Dongdong WANG ; Yanbo ZHANG ; Bowen XUE ; Aiping TAO
Chinese Journal of Interventional Cardiology 2014;(8):501-504
Objective This study was conducted to investigate the clinical outcomes and safety of percutaneous coronary intervention (PCI) to the single-opened vessel lesion among patients with severe left ventricular systolic dysfunction. Methods Twenty-seven patients with severe left ventricular systolic dysfunction (ejection fraction≤35%) undergoing PCI were included. All the patients received PCI only to the single-opened vessel lesion under the conditions of: (1) There were limitations to open chronic total occlusion (CTO);(2) Single-opened vessel lesion was not calcified and tortuous. Clinical outcomes, including success rate of PCI, changes of symptoms in-hospital, brain natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) pre-and one week post-PCI, the major adverse cardiac events (MACE, including death, myocardial infarction and target vessel revascularization) at 30-days after discharged were observed. Results The success rate of PCI was obtained in all 27 patients(100%), and all the patients received drug eluting stent implantation. The symptoms improvement occurred in all patients and the NYHA class improved from grade Ⅳto grade Ⅲin 22 patients(81.5%) in-hospital. Significant differences were noted in the mean BNP and LVEF between pre-PCI and one week post-PCI, BNP[(2699.6±1104.7) pg/ml vs. (737.0 ± 261.7) pg/ml, P<0.05],LVEF[(26.9±5.7)%vs. (36.0±3.41)%, P<0.05)]. No MACE happened in-hospital and at 30-days follow up. Conclusions PCI only to the single-opened vessel lesion among patients with severe left ventricular systolic dysfunction under the condition of limitations to open CTO is safe and can significantly improve clinical outcomes in-hospital and at 30-days follow up, but it must be emphasized that single-opened vessel lesion not with obvious calcification and tortuosity.