1.Non-coding RNAs as therapeutic targets in cancer and its clinical application
Leng XUEJIAO ; Zhang MENGYUAN ; Xu YUJING ; Wang JINGJING ; Ding NING ; Yu YANCHENG ; Sun SHANLIANG ; Dai WEICHEN ; Xue XIN ; Li NIANGUANG ; Yang YE ; Shi ZHIHAO
Journal of Pharmaceutical Analysis 2024;14(7):983-1010
Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.
2.Analysis of a case of Multiple pterygium syndrome due to a novel variant of CHRNG gene.
Yiru CHEN ; Tianying NONG ; Weizhe SHI ; Jiangui LI ; Xuejiao DING ; Yue LI ; Mingwei ZHU ; Hongwen XU
Chinese Journal of Medical Genetics 2023;40(6):686-690
OBJECTIVE:
To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS).
METHODS:
A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis.
RESULTS:
The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS.
CONCLUSION
The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.
Humans
;
Child
;
Female
;
Abnormalities, Multiple/genetics*
;
Malignant Hyperthermia/genetics*
;
Skin Abnormalities/genetics*
;
Heterozygote
;
Mutation
;
Receptors, Nicotinic/genetics*
3. Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice
Xuejiao ZHANG ; Jieting LIU ; Luxin LI ; Peijian CHEN ; Minglu DING ; Mengwei SUN ; Yanhui CHU ; Zhen ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(3):257-265
AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg
4.Awareness and willingness to vaccinate daughters with human papillomavirus vaccines among parents of primary and middle school students
LIANG Hui ; TANG Tingting ; LÜ ; Huakun ; HU Yu ; CHEN Yaping ; PAN Xuejiao ; DING Linling ; HU Xiaosong ; WANG Ying
Journal of Preventive Medicine 2021;33(9):884-888
Objective :
To investigate the awareness of human papillomavirus ( HPV ) vaccine and willingness to vaccinate daughters among parents of primary and middle school students, so as to provide the reference for the promotion of HPV vaccine in primary and middle school girls.
Methods :
Using multi-stage stratified cluster sampling method, the parents of girls in in Grade Four to Nine from schools in Gongshu District of Hangzhou, Xiuzhou District of Jiaxing and Wuxing District of Huzhou were selected. A questionnaire survey was conducted to collect demographic information, HPV vaccine related knowledge and willingness to vaccinate daughters with HPV vaccines. The multivariate logistic regression model was used to analyze the influencing factors for the willingness to vaccinate daughters with HPV vaccines among parents.
Results :
Totally 1 500 questionnaires were sent out, and 1 466 were effectively collected, with an effective rate of 97.73%. There were 313 fathers responded, accounting for 21.35%; and 1 153 mothers responded, accounting for 78.65%. The awareness rate of HPV vaccine was 16.81%. The rate of willing to vaccinate daughters with HPV vaccines was 49.86%. The multivariate logistic regression analysis showed that the patients who ever vaccinated daughters with self-paid vaccines ( OR=1.935, 95%CI: 1.473-2.541 ), knew cervical cancer ( OR=1.424, 95%CI: 1.065-1.904 ), knew HPV vaccine dose ( OR=1.672, 95%CI:1.216-2.301 ), knew the best vaccination period ( OR=1.392, 95%CI: 1.032-1.876 ), knew the need of cervical cancer screening even after vaccination ( OR=1.596, 95%CI:1.227-2.075) were more willing to vaccinate daughters with HPV vaccines, while the parents who thought HPV vaccine expensive ( OR=0.154, 95%CI: 0.099-0.240 ) were less willing to vaccinate daughters with HPV vaccines.
Conclusions
The rates of HPV vaccine awareness and willingness to vaccinate daughters are 16.81% and 49.86% among parents of primary and middle school students. Their knowledge of HPV vaccine and the price of the vaccine may affect their willingness to vaccinate daughters.
5.Toilet facilities and student toilet-using behavior in rural primary schools
SHAO Tang, CHEN Guoliang, ZHAO Liang, ZHAO Jingjing, DING Xuejiao, ZHANG Qi
Chinese Journal of School Health 2019;40(8):1220-1223
Objective:
To understand the current situation of toilet facilities among rural primary schools and toilet-using behavior among primary students,and to provide a reference for improving school environment.
Methods:
Totally 149 students in 2 rural non-boarding primary schools in northern China were selected. and on-site observation and questionnaire survey were used to obtain the current situation of toilet hygiene, toilet time and toilet behavior, as well as feelings towards school toilet. The results of the survey were statistically analyzed by using SAS 9.4.
Methods:
Both two schools were deep pit latrine, the number of pit in female toilets is lower than the requirements of the “Code for design of school”, and the urinal trough and the number of pit in male toilet meet the standard requirements. The average total time of toilet-using was (28.46±11.72)s for boys and (42.48±15.52)s for girls, the difference was of significant difference (t=-7.96, P<0.01). The average actual time of toilet-using is (24.27±9.13)s for boys and (24.69±9.40)s for girls, with no statistical difference. The result showed that school 2 was better than school 1 in the behavior of urinating frequency in toilet, queuing when using toilet, and the way to express needs of toilet-using in class(χ2=11.70,27.19,17.74,P<0.05); senior students use less toilets than lower grade students. The main complains for students in school toilet hygiene is its bad smell(χ2=5.28,13.18,P<0.05).
Conclusion
Primary school students in northern China always take bathroom breaks in the morning, and the average time of toilet-using is different from that of adults. Senior students are more willing to express their toilet needs than lower grade students. Students are not satisfied with the hygiene of school toilets, and the toilet experience is poor.
6.The investigation of using diffusion-weighted magnetic resonance imaging technologies to evaluate the therapeutic effect of esophageal primary carcinoma treatment with chemoradiotherapy
Boyue DING ; Lan WANG ; Chun HAN ; Lihong LIU ; Xuejiao REN ; Li'ang XU ; Shutang LIU
Chinese Journal of Radiological Medicine and Protection 2018;38(10):741-746
Objective To determine the efficacy of primary tumor of esophageal cancer,according to the result of magnetic resonance imaging before and after chemoradiotherapy of esophageal cancer,combined with clinical efficacy evaluation,and to verify the reliable evaluation of the short-term curative effect of magnetic resonance on esophageal cancer,combined with the original CT and esophagogram evaluation criteria.Methods From May 2010 to March 2014,totally 83 patients with esophageal carcinoma treated with 3D-CRT or IMRT were enrolled.The prescribed doses were ranged from 50-64 Gy with median dose of 60 Gy and 1.8-2.0 Gy per fraction,of which 34 of the patients received concurrent chemotherapy of FP or TP.All the patients performed the examinations of DWI,CT scan and esophagogram before and after radiotherapy.The treatment efficacy was evaluated by short-term therapeutic effect evaluation criterion of versions 1989 and 2013 and the hyperintense expression on DWI sequence.Results According to the short-term therapeutic effect evaluation criterion of versions 1989 and 2013 based on the examination of esophagogram and CT scan,45 patients achieved complete remission (CR) after treatment(54.2%) and 38 achieved partly remission(PR) (45.8%) version 1989,while 35 patients achieved CR (42.2%) and 48 achieved PR (57.8%) version vesion 2013.In the two differentcriterions,the local control rate and survival rate of the complete remission group in 1 to 5 years were better than those in the partial remission group.According to the examination of DWI,48 patients' hyperintense disappeared completely at the end of treatment (which was defined to CR),25 patients had a slightly hyperintense expression and 10 patients still had hyperintense expression on DWI sequence (which two defined to PR),the local control and survival rates of the former group were superior to the latter groups (x2 =6.125,11.652,P <0.05).The TE results evaluated by DWI and TE evaluation criterion of version 2013 were compared according to Kappa test,as a result,the Kappa coefficient 0.478.According to the examination of esophagogram,CT scan and DW1,25 patients achieved CR and 58 achieved PR in all exams,and the local control and survival rates of the former group were superior to the latter group (x2 =5.559,10.014,P <0.05).Conclusions The esophagogram and CT based TE evaluation criterion could well indicate local control status of esophageal cancer,and the examination of DWI could afford visualized and quantifying reference information about the TE of esophageal cancer.The expression of hyperintense at the end of treatment may indicate a high risk of recurrence and metastasis.The therapeutic effect evaluated by esophagogram,CT scan and DWI maybe more objective and more accurate.
7.Clinical application of barium radiography and computed tomography-based short-term outcome evaluation criteria in esophageal cancer
Xuejiao REN ; Lan WANG ; Liying CHEN ; Chun HAN ; Boyue DING ; Lihong LIU ; Shutang LIU ; Xiaoning LI ; Chao GAO ; Liang XU
Chinese Journal of Radiation Oncology 2018;27(5):449-454
Objective To explore and improve the feasibility and prognostic value of barium radiography and computed tomography (CT)-based evaluation criteria in evaluation of the short-term efficacy of radiotherapy for esophageal cancer,and to provide a basis for clinical application.Methods The short-term treatment outcomes of 529 patients with esophageal carcinoma receiving three-dimensional radiotherapy from 2004 to 2015 were evaluated by the 2013 version of barium radiography and CT-based evaluation criteria.The local control (LC) and survival rates were calculated using the Kaplan-Meier method.The log-rank test was used for data analysis and univariate prognostic analysis.The agreement between two evaluation criteria was measured by the Kappa coefficient.Results According to the results of the survival analysis in all the patients using the evaluation criteria for short-term treatment outcomes,the 3-,5-,7-,and 9-year LC rates were 78.6%,69.8%,69.8%,and 63.4% in the complete response (CR) group (n=52),and 56.4%,47.9%,46.2%,and 42.4% in the partial response (PR) group (n=409),respectively;the 3-,5-,7-,and 9-year overall survival (OS) rates were 62.7%,49.1%,39.8%,and 39.8% in the CR group,and 29.5%,21.6%,20.6%,and 19.5% in the PR group,respectively;the median OS time was 50,17,and 5 months in the CR group,PR group,and non-response group (n=12),respectively (P=0.000).According to CT measurements,the short diameter of residual metastatic lymph node after radiotherapy was between 0.37-3.40 cm (median value=0.82 em).All patients were divided into groups based on the short diameter of residual metastatic lymph node after radiotherapy with a gradient of 0.5 cm.Patients with short diameters of residual metastatic lymph node of ≤ 1.00 cm had a significantly higher OS rate than those with short diameters of residual metastatic lymph node of> 1.00 cm (P =0.000).The lymph node volume of 1.00 cm3 in the original criteria was replaced by the short diameter of residual metastatic lymph node of 1.00 cm after radiotherapy and treatment outcomes were re-evaluated using the new criteria.The CR group still had significantly higher LC and OS rates than the PR group (P=0.000).There was a good agreement between the two evaluation criteria (Kappa =0.863).Conclusions The barium radiography and CT-based evaluation criteria for short-term treatment outcomes can accurately evaluate the short-term outcomes and predict prognosis in patients with esophageal carcinoma.Replacing the volume in the original criteria with the short diameter of residual metastatic lymph node after radiotherapy achieves similar results in prognostic prediction.
8.Comparison of survival benefits between simultaneous integrated boost intensity-modulated radiotherapy and conventional fractionated radiotherapy for esophageal squamous cell carcinoma
Lan WANG ; Jian LIANG ; Chun HAN ; Li'ang XU ; Lihong LIU ; Xuejiao REN ; Shutang LIU ; Shuman ZHEN ; Boyue DING
Chinese Journal of Radiation Oncology 2018;27(11):965-970
Objective To investigate the survival benefits of simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in the treatment of esophageal squamous cell carcinoma ( ESCC ) . Methods From July 2003 to March 2014,1748 patients with ESCC received 3DCRT or IMRT in a single institution were enrolled in this retrospective study. Among them, 809 patients received conventional fractionated radiotherapy with the standard prescription dose and 110 patients received SIB-IMRT ( SIB-IMRT group).Survival analysis was performed and propensity score matching (PSM 1vs1) was conducted to evaluate and compare the survival benefits between SIB-IMRT and conventional fractionated radiotherapy. Results The baseline characteristics significantly differed between two groups. In the SIB group,the age was significantly younger ( 64 years vs. 66 years, P=0. 001 ) , the percentage of patients with cervical/upper thoracic tumors was considerably higher (53. 6% vs. 31. 0%,P=0. 000) and the proportion of N2 patients was significantly higher ( 21. 8% vs. 13. 7%,P=0. 027) compared with those in the other group. Accordingto the PSM of 1:1, 218 patients were successfully matched. After matching, the clinical data did not significantly differ between two groups. Prior to matching,the median survival time in the standard dose and SIB-IMRT groups were 23 and 21 months (P=0. 638).After matching,the median survival time in the SIB-IMRT group was 22 months,significantly longer than 18 months in the standard dose group (P=0. 000). Subgroup analysis demonstrated that patients with large tumors ( GTV volume>40 cm3 ) and middle/lower thoracic tumors obtained more survival benefits from SIB-IMRT. The median survival time of patients in the standard dose group was 14 months, significantly shorter than 21 months in the SIB-IMRT group ( P=0. 001).The median survival time of patients with middle/lower thoracic tumors in the SIB-IMRT group was 17 months,significantly longer than 9 months in the standard dose group (P=0. 000).Multivariate analysis using Cox regression model indicated that age, tumor site and radiotherapy modality were the independent prognostic factors. The HR of SIB-IMRT was 0. 551(P=0. 000),which was a factor for survival benefits. Conclusions SIB-IMRT possesses potential survival benefits for ESCC compared with conventional fractionated radiotherapy. Patients with large tumors and middle/lower thoracic tumors are more prone to obtaining benefits from SIB-IMRT than their counterparts.
9.Long-term efficacy of concurrent chemoradiotherapy at different radiotherapy doses in treatment of esophageal carcinoma
Xuejiao REN ; Lan WANG ; Chun HAN ; Boyue DING ; Jing HAN ; Yang YOU
Chinese Journal of Radiation Oncology 2017;26(9):1006-1011
Objective To compare the local control (LC), long-term overall survival (OS), and clinical adverse reactions in esophageal carcinoma patients receiving concurrent chemoradiotherapy at different radiotherapy doses.Methods A total of 373 esophageal carcinoma patients who received concurrent chemoradiotherapy in our hospital during 2004-2013 were included in this retrospective study.These patients were divided into<60 Gy group (n=99), 60 Gy group (n=155), and>60 Gy group (n=119) based on the dose of radiation.The Kaplan-Meier method was used to calculate LC and OS rates;the log-rank test was used for survival comparison and univariate prognostic analysis;the Cox model was used for multivariate prognostic analysis.Results The 3-, 5-, 7-, and 10-year sample sizes were 97,96,56, and 38 in the<60 Gy group, 146,141,72, and 17 in the 60 Gy group, and 118,115,56, and 20 in the>60 Gy group.The 3-, 5-, 7-, and 10-year LC rates were 55.3%, 51.4%, 48.9%, and 48.9% in the<60 Gy group, 65.1%, 60.1%, 55.1%, and 55.1% in the 60 Gy group, and 49.4%, 45.1%, 37.7%, and 37.7%(8-year) in the>60 Gy group (P=0.020).The 3-, 5-, 7-, and 10-year OS rates were 35.4%, 26.1%, 22.0%, and 22.0% in the<60 Gy group, 49.0%, 41.3%, 32.1%, and 28.9% in the 60 Gy group, and 31.1%, 25.2%, 14.5%, and 12.9%(8-year) in the>60 Gy group (P=0.000).The univariate analysis showed that for stage Ⅱ esophageal carcinoma patients with gross tumor volume (GTV) ≤44 cm3, the LC rate was higher in the 60 Gy group than in the<60 Gy group (P=0.040,0.035), and the OS rate was higher in the 60 Gy group than in the other two groups (P=0.001,0.003 and P=0.045,0.006).Similarly, for stage Ⅲ esophageal carcinoma patients with GTV>44 cm3, the LC rate was higher in the 60 Gy than in the>60 Gy group (P=0.011,0.015), and the OS rate was higher in the 60 Gy group than in the other two groups (P=0.045,0.006 and P=0.033,0.002).The incidence rates of acute radiation esophagitis and radiation pneumonia were significantly higher in the>60 Gy group than in the other two group (P=0.007,0.033).Furthermore, the multivariate analysis indicated that radiotherapy dose, T stage, and N stage were independent prognostic factors for esophageal carcinoma (P=0.004,0.008,0.037).Conclusions Concurrent chemoradiotherapy at 60 Gy is most efficacious for patients with esophageal carcinoma, and the radiotherapy dose of>60 Gy significantly increases the incidence of adverse reactions.
10.Role of H4K20me1 and base excision repair-related genes in repairing DNA damage induced by arsenic pollution through coal burning
Jun LI ; Lang XIE ; Xuejiao DING ; Qi WANG ; Bing LIANG ; Aihua ZHANG
Chinese Journal of Endemiology 2017;36(11):781-786
Objective To investigate the global level of histone 4 lysine 20 monomethylation (H4K20me1) and expression of base excision repair related mRNA in coal-burning-borne endemic arsenism patients and to analyze its relationship with DNA damage,in order to provide a scientific basis in deepening the interpretation of the role of arsenic in inhibiting repair of DNA damage.Methods In 2014,47 hair samples,blood samples and skin tissue samples of the cases in Xingren County Guizhou Province were collected from the voluntary surgical treatment patients with endemic arsenism (15 general pathological change cases,14 precancerous cases and 18 cancerous cases) and 12 controls.The hair arsenic content was tested via the inductively coupled plasma-mass spectrometry method.The expression of histone H4K20me1 in skin tissues was detected via the immunohistochemistry method;quantitative real-time polymerase chain reaction was used to detect the mRNA levels of poly (ADP-ribose) polymerase (PARP1),N-methylation of purine-DNA-glycosylation (MPG) and X-ray repair cross complementary gene 1 (XRCC1);and DNA damage in peripheral blood was detected by single cell gel electrophoresis test,the level of H4K20me1 in peripheral blood cells was detected by using a sandwich enzyme-linked immunosorbent assay.Results Compared with the control group [median (25 ~ 75 percentile):0.15 (0.07-0.23) μg/L],the hair arsenic content in the case group [0.34 (0.17-0.51) μg/L] was significantly increased (Z =6.037,P < 0.05).Compared with the control group (0.32 ± 0.13,0.17 ± 0.12),the modification level of H4K20me1 in peripheral blood with cancerous group (0.62 ± 0.11) was significantly increased,the modification levels of H4K20me1 (0.54 ± 0.20,0.83 ± 0.10) in skin tissues were increased in the precancerous group and cancerous group (P < 0.05).Compared with the control group [0.95 (0.50-1.49),1.12 (0.98-1.48),0.96 (0.67-1.17)],the mRNA expression levels of PARP1 and MPG in cancerous group [0.37 (0.30-0.44),0.38 (0.15-0.48)] were significantly decreased;the mRNA expression levels of XRCC1 [0.48 (0.38-0.89),0.32 (0.20-0.55)] were significantly decreased in the precancerous group and cancerous group (P < 0.05).Compared with the control group (1.19 ± 0.55,1.27 ± 0.51),Tail DNA% and Tail moment were significantly increased in the general pathological change group (6.49 ± 0.98,6.60 ± 1.11),the precancerous lesion group (11.22 ± 1.40,10.07 ± 1.11),and the cancerous group (20.38 ± 1.72,27.01 ± 1.78,P < 0.05).There was a positive correlation between the degree of skin lesion and modification level of H4K20me1 in peripheral blood and skin tissues and DNA damage levels (TailDNA%,OTM,r =0.885,0.855,0.806,0.883,P < 0.05).There was a positive correlation between modification level of H4K20me1 in peripheral blood and level of DNA damage (TailDNA%,OTM),the level of H4K20me1 protein expression in skin (r =0.535,0.804,0.754,P < 0.05),and a negative correlation with mRNA expression of MPG,XRCC1 and PARP1 (r =-0.563,-0.514,-0.550,P < 0.05).There was a positive correlation between the modification level of H4K20me1 in skin and DNA damage levels (TailDNA%,OTM,r =0.602,0.875,P < 0.05),and a negative correlation with mRNA expression of MPG,XRCC1 and PARP1 (r =-0.492,-0.502,-0.552,P < 0.05).Conclusion The arsenic pollution of coal burning may affect the level of H4K20me1 modification,inhibit mRNA transcriptional expression of PARP1,MPG and XRCC1 genes related with base excision repair,which may lead to increased DNA damage and participate in the occurrence and development of arsenic poisoning skin lesions.


Result Analysis
Print
Save
E-mail