1.Roles of BTG3 Expression in Gastric Cancer and Mechanism for Its Tumor Suppression Function
Huachuan ZHENG ; Daofu SHEN ; Xuefeng YANG ; Wenfeng GOU ; Shuang ZHAO ; Wenlu ZHANG
Journal of China Medical University 2015;(10):877-882
Objective To clarify the clinicopathological significance and the reversing effects of BTG3 expression on the aggressive phenotype in gastric cancer. Methods BTG3 expression was detected in gastric cancer tissues by on tissue microarray and immunostaining. BTG3?expressing plasmid was transfected into MKN28 and MGC803 cells,the proliferation,cell cycle,differentiation and autophagy were analyzed by CCK?8,PI staining,alkaline phosphatase activity and GFP?LC?3B transfection,respectively. Results BTG3 overexpression inhibited cell proliferation,in?duced S/G2 arrest,differentiation and autophagy in both cells(P<0.05). BTG3 expression was decreased in gastric cancer in comparison with the adjacent mucosa(P<0.05),and positively correlated with venous invasion and dedifferentiation of the cancers(P<0.05). Conclusion BTG3 ex?pression contributes to gastric carcinogenesis and subsequent progression. BTG3 overexpression can reverse the aggressive phenotypes,which could be employed as a potential target for gene therapy of gastric cancer.
2.Clinicopathological Significance and Relevant Molecular Mechanisms of Beclin 1 in Gastric Cancer
Huachuan ZHENG ; Daofu SHEN ; Xuefeng YANG ; Shuai SHI ; Yang GAO ; Shuang ZHAO ; Wenlu ZHANG
Journal of China Medical University 2015;(12):1061-1065
Objective to explore the role of Beclin 1 in gastric carcinogenesis and subsequent progression. Methods MkN28 cells were trans-fected with Beclin 1-expressing plasmid,and then the proliferation and cell cycle was measured by CCk-8 and PI staining. Beclin 1 expression was examined by immunohistochemistry and in situ hybridization on tissue microarrays containing gastric cancers,adjacent non-neoplastic mucosa,and metastatic lymph node. the correlation with the tumorgenesis,clinicopathological and prognostic parameters was analyzed. Results Beclin 1 overex-pression resulted in G2 arrest of MkN28 cells and reduced the proliferation. Beclin 1 mRNA was highly expressed in gastric cancer than matched mu-cosa by ISH(P < 0.05). Beclin 1 was highly expressed in male than female patients with gastric cancer(P < 0.05). the elder patients with gastric cancer had higher Beclin 1 expression than younger ones(P < 0.05). the diffuse-type carcinomas showed less Beclin 1 expression than intestinal and mixed type ones(P < 0.05). kaplan-Meier analysis indicated that Beclin 1 expression was positively correlated to favorable prognosis of the can-cer patients(P < 0.05). Conclusion Beclin 1 expression is closely linked to pathogenesis,metastasis and differentiation of gastric cancer. Beclin 1 might be employed to indicate the favorable prognosis of gastric cancer patients and regarded as a target of gene therapy.
3.99Tcm-EHIDA SPECT combined with planar hepatobiliary scintigraphy for the differentiation between infant biliary atresia and neonatal hepatitis
Wenlu ZHENG ; Yue CHEN ; Zhanwen HUANG ; Liang CAI ; Wenbin DONG ; Bin LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(4):296-299
Objective To evaluate the value of 99Tcm-EHIDA SPECT combined with planar hepatobiliary scintigraphy (combined scintigraphy) in the differentiation of infant biliary atresia (BA) from neonatal hepatitis (NH).Methods This is a retrospective study on 32 infants with cholestasis (18 males,14 females;age:28-83 d) from June 2013 to June 2014.All infants underwent sequential 99Tcm-EHIDA hepatobiliary planar scintigraphy and combined scintigraphy,and the diagnostic efficacy of the 2 methods for differentiating infant BA from NH was analyzed by x2 test.Results In sequential planar scintigraphy,the diagnostic sensitivity,specificity,accuracy,positive predictive value and negative predictive value were 76.2% (16/21),6/11,68.8% (22/32),76.2% (16/21) and 6/11,respectively.In combined scintigraphy,the diagnostic parameters were 95.2% (20/21),8/11,87.5% (28/32),87.0% (20/23) and 8/9,respectively.Combined scintigraphy correctly identified 4 BA cases that were misdiagnosed as NH by planar scintigraphy.The sensitivity of combined scintigraphy was significantly higher than that of planar scintigraphy (x2 =4.285,P<0.05),while no significant difference was found in the other diagnostic parameters (x2 =0.061-0.405,all P>0.05).Conclusions Combined scintigraphy has incremental value for the differentiation of infant BA from NH.
4.Association of polymorphisms in transcription factor 7-like 2(TCF7L2) gene with type 2 diabetes in Chinese Han population
Zhihong WANG ; Suhua ZHANG ; Zengchan WANG ; Lilin GONG ; Rong LI ; Wei REN ; Ruizhi ZHENG ; Maorong WANG ; Wenlu ZHANG ; Qingfeng CHENG ; Song LIANG ; Xiaoli WAN ; Lanying ZHANG ; Jun HE
Chinese Journal of Endocrinology and Metabolism 2009;25(2):139-143
Objective To study the association of transcription factor 7-like 2(TCF7L2)polymorphisms with tvpe 2 diabetes mellitus in Chinese Han population. Methods Two polymorphisms (rs7903146 and rs12255372)of TCF7L2 gene were genotyped in 446 patients with type 2 diabetes mellitus(T2DM group)and 303 normal subiects (NC group) by PCR-restriction fragment length polymorphism(PCR-RFLP).Waist circumference.body mass index,plasma glucose,serum insulin,lipid profiles,high-sensitivity C-reactive protein and non-esterified fatty acid were measured.Homeostasis model assessment of insulin resistance(HOMA-IR)and β-cell function(HOMA-β)were calculated.Results (1) In T2DM group,T allele frequency and CT,TY geno tvpe frequeneies of rs7903146 were significantly higher than those in NC group(0.093,0.150,0.018 vs 0.043, 0.079,0.003,respectively,a11 P
5.Mutations of mitochondrial tRNAand their connection with hearing loss.
Wenlu FAN ; Xiaowen TANG ; Binjiao ZHENG ; Minxin GUAN ; Ling XUE
Chinese Journal of Medical Genetics 2017;34(1):128-132
Mitochondrial tRNAgene mutation is closely related to acoustic nerve deafness. Some mutations can affect the structure and transcriptional processing of tRNA, for instance m.7444G>A mutation in tRNAprecursor 3' side, m.7472 insC as well as m.7511T>C mutations in the stem and ring of tRNA, may influence tRNAstability, thus affect the synthesis of mitochondrial peptides, reduce the production of ATP and cause deafness. This article focuses on mitochondrial tRNAgene mutations as well as the mechanism underlying hearing loss.
Amino Acid Sequence
;
Base Sequence
;
Genetic Predisposition to Disease
;
genetics
;
Hearing Loss
;
genetics
;
Humans
;
Mitochondrial Proteins
;
biosynthesis
;
genetics
;
Mutation
;
Nucleic Acid Conformation
;
RNA
;
chemistry
;
genetics
;
RNA, Transfer, Ser
;
chemistry
;
genetics
6.Analysis on the initial state of postlingual deafness in adult patients after cochlear implantation
Haizhen LI ; Xiujin ZHENG ; Xueping SUN ; Wenlu ZHANG
Chinese Journal of Modern Nursing 2014;20(4):413-415
Objective To analysis the re-hearing expectations and the need for auditory training and the time of adaptation exchanges after cochlear implantation .Methods Sixteen cases of adult postlingual deafness, which were selected, from 2002 to 2011, were treated by cochlear implantation .9 cases participated in speech training right after cochlear implantation , and 7 cases didn ’ t participate in speech training .In the initial stage, the patients were given the tone and input hearing test with voice frequency in the natural environment.The auditory training was for 2 hours a day, which included single and combined training .The training method was comprehensive , including auditory speech perception , writing and verbal expression .The training focused on the coherence and clarity of oral Reading .One training course was 3 -10 weeks .The efficacy of the training with the combination of sound and the ability to adapt to society was analyzed . Results In 10 cases joining the training , 4 cases instantly began to auditory training after cochlear implantation and lasted for more than 5 weeks.1 case discontinuously trained for 4 weeks, and other 5 cases trained transiently ( less than 3 ~4 days ) .6 cases refused to participate in the training process after cochlear implantation .Assessed by the “the lowest auditory function test vocabulary”, the distinguish rate of 5 patients was 90.3%after training for more than 4 weeks, who gradually adapted to working and learning environment after 5-7 months, and gained normal communication after 1.5-2.0 years.The distinguish rate of 5 patients was 36.0%after training for several days , and 2 patients cannot accomplish the test .Besides, the 6 patients without participation the training program cannot finish the assessment for over 2 years after cochlear implantation.Conclusions Cochlear implantation provides patients with the possibility of re-hearing, and the postoperative training can help patients in communicating in social life .A variety of factors can affect the efficacy of re-hearing adult patients with post-lingual hearing after cochlear implantation .
7.Effect of auditory enlightenment and whole ability training in hearing impaired children with inner ear malformations
Haizhen LI ; Xiujin ZHENG ; Dongsheng HUANG ; Chen ZHANG ; Hong WEI ; Wenlu ZHANG ; Xueping SUN
Chinese Journal of Modern Nursing 2014;20(22):2770-2772
Objective To explore the methods of auditory enlightenment and whole ability training in severe hearing impaired children with inner ear malformations and growth retardation .Methods Eleven severe hearing impaired children with inner ear malformations were chosen , and received the methods of multiple stimuli including auditory, vision, tactile sensation, large and fine motor and so on in order to train their skills including the response and discrimination of sounds , language , and cognition and so on .Results The abilities of hearing and sense were gradually establishment in children 3 months after the training .Seven children could perceive clearly sound , and finish the hearing examination after training 6-13 months so as to lay the foundation for behavioral responses after the cochlear implantation surgery .Two children finished the hearing assessment after the hearing compensation through the audiphone .Conclusions The methods of multiple stimuli in the different sense at the same time can promote the formation of auditory consciousness and auditory nerve loop in infants with inner ear malformations .
8.Importance analysis of early detection and prevention for children abnormal with abnomal hearing and speechdy
Haizhen LI ; Xiujin ZHENG ; Chen ZHANG ; Dongsheng HUANG ; Wenlu ZHANG ; Xueping SUN
Chinese Journal of Modern Nursing 2014;20(35):4469-4473
Objective To explore children with audition symptom as normal but heterophthongia impacting on the process of their growth , and try to find out the symptom of abnormal speech and hearing to prevent and cure early .Methods Fifty six children were selected at the age of 6 months to 8 years old whose development of audition and speech had not reached the normal norm and known their information relative growth factors such as medical history , present illness , family medical history and environment of growth inside out .We assessed the speech and audition of all cases by clinical objective and subjective audition test and they shown different level of audition damage .We provided different methods to prevent and cure disorders according to inducing factors .Results The characteristic of children , whose right and/or left ear had different damage ( earshot:35 -120 dB ) , usually could not arouse attention especially at early linguistic stage because of inapparent hearing and speech disorders .The delayed diagnosed audition problem already leaded that sixteen children from 4 -8 years old acquired the problems of inappropriate response to voice , simple and vague language and restricted study and twenty cases obtained no response to voice , delayed development of audition comparing with peers , and expressed their demand by body language until 2 to 4 years old until they sought medical advice .Neonatal audition had not passed first and second screen and the level of audition damage were at range of 20-90 dB; however , parents believed neonate could develop naturally when neonate grown up so that they attended training without consistency and worn hearing aid incontinuity .These kind of behavior leaded that neonate acquired medical treatment until 1.5 to 2 years and some reflections had been built up or delayed . Conclusions Children with a similar audition as normal children but heterophthongia are unapparent at early stage, but it will slight show out when they grow up .Parent should comprehend the children ’ s process of hearing and language development and try to find out language and hearing problem as earlier as possible .Early detection could decrease growth gab between children with audition problems and normal children .
9.Safety and efficacy of 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer
Yu ZHANG ; Hongyu YANG ; Xinyi LIN ; Dan SU ; Yu ZHANG ; Wenlu ZHENG ; Zhanwen HUANG ; Yue CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(9):522-527
Objective:To evaluate the safety and efficacy of 225Ac-prostate specific membrane antigen (PSMA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Methods:Eleven patients (age (70.0±8.8) years) with mCRPC who were treated with 225Ac-PSMA-617 between July 2021 and October 2023 in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. In order to assess efficacy, the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria were used to evaluate the changes in prostate specific antigen (PSA) level after the treatment. 68Ga-PSMA-11 PET/CT imaging was performed at the baseline and after the treatment, and molecular imaging response was assessed using the modified PET response criteria in solid tumors (PERCIST) 1.0. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Toxicity was assessed by common terminology criteria for adverse events version 5.0 (CTCAE 5.0). The paired t test or Wilcoxon signed rank test was used to compare the parameters before and after treatment. Results:Post-treatment PSA levels were significantly lower than pre-treatment in 9 of 11 patients (17.83(4.74, 41.25) vs 124.33(77.85, 784.22) μg/L; z=-2.67, P=0.008), and 6 of them decreasing by more than 50% and 2 patients experienced progressive disease (PD) with PSA levels rising by more than 25%. Post-treatment 68Ga-PSMA-11 PET/CT showed that 7 patients achieved partial response (PR), 2 patients achieved stable disease (SD), and 2 patients were with PD. The OS was 12.0(10.0, 18.0) months and PFS was 8.0(6.0, 11.0) months in 11 patients. There were no statistically significant differences after therapy in WBC counts, Hb, PLT, creatinine, glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, total bilirubin ( z values: from -1.07 to 0.00, t values: from -0.77 to 1.76, all P>0.05). No grade Ⅲ/Ⅳ nephrotoxicity or salivary gland toxicity was observed. Conclusion:225Ac-PSMA-617 is a promising novel therapeutic option for mCRPC with favorable safety and tolerability.
10.Mechanism of Yangxin Dingji Capsules in Preventing Ventricular Arrhythmia Based on TAK1/MKK3/p38 MAPK Pathway
Mian LI ; Zheng ZHANG ; Xinyue LI ; Xue TIAN ; Wenlu ZHENG ; Jinwei WU ; Gang LIU ; Wenjie LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):86-95
ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol (ISO)-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 (TAK1)-mitogen-activated protein kinase kinase 3 (MKK3)-p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group, a model group, a propranolol group, a low-dose Chinese medicine group, and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg-1·d-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg-1·d-1, respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram (ECG) changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1) were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Reactive oxygen species (ROS) expression was detected using immunofluorescence. Protein expression levels of TAK1, phosphorylated TAK1 (p-TAK1), MKK3, phosphorylated MKK3 (p-MKK3), p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), IL-1β, and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group, the model group showed significant ventricular arrhythmia in ECG, with an increased arrhythmia score (P<0.01). Pathological damage to myocardial tissue was evident, and serum levels of cTnI, CK-MB, IL-1β, TNF-α, and TGF-β1 were elevated (P<0.01). The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased (P<0.01). ROS level and protein expression of p-TAK1, p-MKK3, p-p38 MAPK, and p-NF-κB were elevated in myocardial tissue (P<0.01). In the propranolol and Chinese medicine groups, the incidence of sustained ventricular tachycardia (SVT) and arrhythmia scores were significantly reduced compared to model group (P<0.05, P<0.01). Pathological damage to cardiomyocytes was alleviated, and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced (P<0.01), with a noticeable reduction in related molecules in the p38 MAPK pathway (P<0.05, P<0.01). ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway, thereby exerting a protective effect on myocardial cells, with TAK1 being a potential target.