1.Relationship between NFKB1 and LHX2 gene polymorphisms and esophageal cancer susceptibility
ZHANG Wenluo ; ZHU Lin ; WANG Yan ; LIU Guangchao ; WANG Wenxiang ; CAI Yingbin
Journal of Preventive Medicine 2025;37(4):350-355
Objective:
To explore the relationship between nuclear factor-kappa B subunit 1 (NFKB1) and LIM-homeobox gene 2 (LHX2) polymorphisms and esophageal cancer susceptibility, so as to provide the reference for the prevention and treatment of esophageal cancer.
Methods:
A total of 100 patients with primary esophageal cancer diagnosed at the Affiliated Tumor Hospital of Xinjiang Medical University from 2019 to 2023 were selected as the case group, and 100 healthy individuals undergoing physical examination during the same period of time were selected as the control group. Demographic information, disease history and lifestyle data were collected through questionnaire surveys. The single nucleotide polymorphisms at the rs28362491 and rs4648068 loci of NFKB1 gene as well as rs10760310 and rs10121751 loci of LHX2 gene were detected using multiplex high-temperature ligase detection reaction technology. The relationship between these loci and esophageal cancer susceptibility were analyzed using a multivariable conditional logistic regression, linkage disequilibrium and haplotype analysis. The impact of the interaction between the above-mentioned loci and environmental factors on esophageal cancer susceptibility using the generalized multifactor dimensionality reduction (GMDR) method.
Results:
The case group comprised 73 males and 27 females, with a mean age of (64.02±8.90) years. The control group included 73 males and 27 females, with a mean age of (64.54±9.43) years. The genotype distributions of rs28362491, rs4648068, rs10760310 and rs10121751, loci in both groups conformed to Hardy-Weinberg equilibrium (all P>0.05). Multivariable conditional logistic regression analysis showed that rs10760310 and rs10121751 loci of LHX2 gene were associated with the esophageal cancer susceptibility (both P<0.05). The overdominant model of rs10760310 loci of LHX2 gene had the lowest Akaike information criterion value (OR=0.22, 95%CI: 0.10-0.47). GAA haplotypes at rs4648068, rs10760310 and rs10121751 loci were associated with a lower risk of esophageal cancer susceptibility (OR=0.26, 95%CI: 0.13-0.50). GMDR analysis revealed a statistically significant interaction between rs10760310 loci and smoking on esophageal cancer susceptibility (P<0.05, cross-validation consistency coefficient: 10/10).
Conclusion
The rs10760310 and rs10121751 loci polymorphisms of LHX2 gene may be associated with esophageal cancer susceptibility, and there is an interaction between rs10760310 loci and smoking on the esophageal cancer susceptibility.
2.Molecular epidemiology of coxsackievirus A16 associated with hand, foot and mouth disease in Fujian province, China from 2020 to 2023
Linfeng LI ; Shujing LI ; Wenxiang HE ; Yuwei WENG ; Ying ZHU ; Wei CHEN
Chinese Journal of Experimental and Clinical Virology 2024;38(5):547-551
Objective:To investigate the molecular epidemiological characteristics of coxsackievirus A16 (CVA16) in Fujian province from 2020 to 2023.Methods:The epidemiological characteristics of CVA16 associated hand, food and mouth disease (HFMD) in Fujian province from 2020 to 2023 was analyzed. The complete VP1 gene of CVA16 was amplified by RT-PCR and then sequenced, and genetic evolution was analyzed by MEGA X and other softwares.Results:From 2020 to 2023, there were 13 120 cases of HFMD in Fujian province, and the proportion of HFMD which caused by CVA16 was 16.5% (2 160/13 120). From 2020 to 2023, the proportion of accounted cases was 4.7% (94/2 019), 14.1% (457/3 243), 47.6% (1 521/3 199) and 1.9% (88/4 659) respectively. HFMD caused by CVA16 was mainly concentrated in children aged 1 to 5 years, and most of them were 3 years old. The genetic evolution and genotype analysis of 92 complete VP1 gene sequences obtained from 2020 to 2023 showed that the genetic distance between CVA16 strains in Fujian province and the prototype strain was far away. The CVA16 genotype in Fujian province from 2020 to 2023 has three clusters of B1a, B1b and B1c, among which the composition ratio of B1a and B1b in Fujian province in 2020 was 40% and 60% respectively. In 2021, B1a and B1b accounted for 81.8% and 18.2% respectively. Only B1a in 2022; in 2023, there were B1a, B1b and B1c, which respectively accounted for 44.4%, 7.4% and 48.2%. During the period from January to September, B1a was the main cluster. After October we observed an emergence of B1c cluster, which had never been found in Fujian province and was rare in China, was detected and became the dominant cluster.Conclusions:The evolutionary cluster of CVA16 dominant changed from B1b in 2020 to B1a in 2021-2023. After October 2023, the newly discovered B1c became the dominant cluster in Fujian province.
3.Study on the development of foot arch and rehabilitation treatment plan for children with spastic diplegia in cerebral palsy gross motor function classification system grade Ⅰ-Ⅱ
Funing GAO ; Jian TANG ; Wenxiang CHEN ; Lei ZHANG ; Min ZHU
Chinese Journal of Child Health Care 2024;32(5):484-490
【Objective】 To investigate the development of the foot arch and develop a rehabilitation treatment plan for children with spastic diplegia of cerebral palsy gross motor function classification(GMFCS) system grade Ⅰ-Ⅱ. 【Methods】 Fifty children with spastic diplegia and flat exostosis with GMFCS grade Ⅰ-Ⅱ were selected into this study, and were divided into observation group (n=25) and control group (n=25) using the random number table method. The control group received conventional exercise therapy, while the observation group received arch correction exercises additionally. Both groups underwent treatment once a day for 5 days a week. Children in both groups were evaluated before and 6 months after the intervention. The arch index F, electronic plantar pressure measurement index, and the D and E scores of the Gross Motor Function Measure (GMFM-88) were used to assess the severity of clubfoot and the level of motor development. 【Results】 Bofore intervention, there were no significant differences in the arch index F, electronic plantar pressure measurement index, and GMFM-88 score between the observation group and the control group (P>0.05). After 6 months of intervention, the scores of arch index F(t=9.89, 5.35), and GMFM-88 (t=6.59, 3.46) in both groups increased significantly(P<0.05). The scores of foot arch index F (26.08±0.73) and GMFM-88 (30.24±7.94) in the observation group and control group were significantly higher than those in the control group (25.34±0.64, 25.20±7.06) (t=3.81, 2.37, P<0.05). Plantar pressure pictures showed a gradual increase in lateral foot pressure compared to medial pressure, and a decrease in pressure in the midfoot arch area, indicating a decrease in foot valgus and progressive development of the arch. 【Conclusion】 The comprehensive rehabilitation therapy technique incorporating arch correction and gymnastics treatment can promote the arch development in children with GMFCS grade Ⅰ-Ⅱ spastic diplegia, which is important for improving their foot and ankle function and motor development level.
4.Establishment of a high performance liquid chromatography method for the detection of CD38 enzyme activity in blood
Xianghui ZHAO ; Xiaoxiao BU ; Hanyu ZHU ; Hongxia LI ; Jihua SHI ; Siming WANG ; Hongna MU ; Ziyun LI ; Zhu WU ; Jun DONG ; Wenxiang CHEN ; Ruiyue YANG
Chinese Journal of Laboratory Medicine 2023;46(10):1074-1082
Objective:A high performance liquid chromatography (HPLC) method was developed to determine the enzymatic activity of CD38 in blood, which was the major enzyme responsible for consuming nicotinamide adenine dinucleotide (NAD). Additionally, the study aimed to detect the differences in CD38 enzymatic activity among individuals of varying ages and health statuses.Methods:A 50 μl whole blood matrix and enzyme reaction substrate of 150 μl β-NAD at a concentration of 500 μmol/L were selected for the analysis. To eliminate the impact of endogenous β-NAD, the whole blood sample was pre-incubated at 37 ℃ for 20 minutes before adding the substrate. The reaction was terminated by perchloric acid (PCA) after incubation at 37 ℃ for 40 min. The change in product nicotinamide (NAM) before and after the enzymatic reaction was measured by HPLC to calculate the CD38 activity. The linearity, limit of detection, limit of quantification, precision, and stability of the method were evaluated. The CD38 enzymatic activities in 60 healthy volunteers and 30 colorectal cancer patients in blood were determined by the developed method.Results:Pre-incubation at 37 ℃ for 20 minutes eliminated the effect of endogenous β-NAD. The correlation coefficient of NAM was 0.999 in the concentration range of 0.1-3.2 μmol/L, with limit of detection of 0.5 nmol/L and limit of quantification of 2.1 nmol/L. The average within-run imprecision ( CV) and total CV were 3.22%-4.03% and 2.91%-4.70%, respectively. The recovery rate ranged from 94.82% to 96.81%. The CD38 activity of whole blood was stable by storage at 4 ℃ for 48 hours, storage at room temperature for 8 hours, thawing of frozen whole blood at room temperature for 2 hours, or repeated freeze-thawing three times. NAM, NAD standards, and pre-treatment samples were stable after 48 hours at 4 ℃ and 8 hours at room temperature. CD38 activity gradually decreased with increasing concentration of the added CD38 inhibitor 4-aminoquinoline derivative (78c). Measurement of 60 healthy physical examination population samples showed significantly higher CD38 enzyme activity in the elderly group than that in the young group ( t=-2.776, P=0.007) and measurement of 30 colorectal cancer patients showed significantly higher CD38 enzyme activity than that in healthy people ( t=-2.572, P=0.012). Conclusion:The established HPLC method for determining CD38 enzymatic activity is characterized by its simplicity, efficiency, accuracy, and reproducibility. This technique serves as a valuable tool for investigating aging and aging-related diseases.
5.Molecular epidemiological characteristics of hand, foot and mouth disease-associated coxsackievirus A2 in Fujian province, China, 2011-2020
Ying ZHU ; Wei CHEN ; Wenxiang HE ; Yuwei WENG
Chinese Journal of Experimental and Clinical Virology 2022;36(4):417-423
Objective:To study the epidemiological and molecular characteristics of coxackievirus A2 (CV-A2) associated with hand, foot and mouth disease (HFMD) in Fujian province, 2011-2020.Methods:Descriptive epidemiological method was used to analyze the epidemiological characteristics of CV-A2. Case information was collected in the laboratory of Fujian Provincial Center for Disease Control and Prevention from 2011 to 2020. The VP1 gene obtained by first-generation sequencing and the complete genome obtained by second-generation sequencing were made phylogenetic analysis and recombination analysis by Mega X and Simplot3.5.1.Results:From 2011 to 2020, there were 35 HFMD-associated CV-A2 cases in Fujian province, most of whom aged 1 to 2 years (28 / 35), and the gender ratio of male to female was 2.5∶1 (25 / 10). Phylogenetic tree of VP1 region showed that CV-A2 in Fujian province was mainly distributed in the evolutionary branches of D1 and C1 subgenotype, only one strain (2019FJPT064) belonged to C1 subgenotype and the other 27 strains were grouped under D1 subgenotype. Among them, 4 isolates from 2011 to 2012 belonged to cluster 1 of D1 subgenotype, and the other two isolates from 2011 to 2012 and those after 2012 belonged to cluster 2 of D1 subgenotype. The complete genome length of 6 CV-A2 strains were about 7 393 to 7 402 bp. The homology of the nucleic acid sequences in the VP1 region of 6 CV-A2 strains and the CV-A2 prototype strain were 80.3%-81.7%, while in the other regions were 72.7%-86.2%. The phylogenetic tree of P2 region showed that 6 CV-A2 strains had a close evolutionary distance with the coxackievirus A4 (CV-A4) and the phylogenetic tree of P3 region showed that 2011FJFZ027, 2012FJQZ311 and 2020FJPTN040 had close evolutionary distance with coxackievirus A6 (CV-A6), coxackieviru A14 (CV-A14), coxackievirus A8 (CV-A8), respectively. Recombination analysis showed that 2011FJFZ027, 2012FJQZ311 and 2020FJPTN040 maybe evolved from recombinant CV-A6 strain (GenBank accession number: KR706309), CV-A14 strain (GenBank accession number: KP036482) and CV-A8 strains (GenBank accession number: KM609475 and MT648786) in non-structural protein region.Conclusions:HFMD-associated CV-A2 was sporadic in Fujian province from 2011 to 2020. The D1 subgenotype of CV-A2 was persistently circulating in Fujian province. From 2011 to 2012, the cluster 1 of D1 subgenotype was the dominant type, and then it shifted to the cluster 2 to take its place after 2012. CV-A2 strains in Fujian were frequently recombined in diversity patterns.
6.Genetic characteristics and recombination analysis of hand, foot and mouth disease related coxsackievirus A5 in Fujian province from 2011 to 2020
Wenxiang HE ; Ying ZHU ; Wei CHEN ; Yuwei WENG
Chinese Journal of Experimental and Clinical Virology 2022;36(6):678-684
Objective:To investigate the gene characteristics and recombination of coxsackievirus A5(CV-A5)in Fujian province.Methods:The VP1 regions of CV-A5 strains from positive samples of hand, foot and mouth disease (HFMD) collected from all cities in Fujian province from 2011 to 2020 were amplified by reverse transcription nested polymerase chain reaction (RT-nPCR), then sequenced and identified the subgenotypes. CV-A5 strains were isolated in rhabdomyosarcoma (RD) cells. The isolated virus strains were sequenced by next generation sequencing to obtain the whole genome sequences. MEGA7.0 was used for phylogenetic analysis. RDP4 and SimPlot 3.5.1 softwares were used to analyze viral gene recombination.Results:Total thirty-one HFMD related CV-A5 cases were detected in Fujian province from 2011 to 2020, mainly in children aged 1 to 2 years (16/31), with a male/female ratio of 2.1∶1 (21/10), including 3 severe cases and 1 deceased case. CV-A5 subgenotyping was successful in 27 cases, all of them belonged to E1 subgenotype. The whole genome sequences of six CV-A5 strains were obtained, and the homology with the prototype strain Swartz was 81.1%-81.6%. Phylogenetic analysis results based on the sequences of whole genome, P1, P2 and P3 regions showed that the virus strain 2017FJFZ239 is a suspected recombinant strain, which was distributed in the same branch as CV-A5 reference strains (GenBank accession number: MW079817 and MN663160) in P2 and P3 regions. Analyzing with RDP4 showed that the virus strain 2017FJFZ239 had the same recombination event with CV-A5 reference strains (GenBank accession number: MW079817 and MN663160) and the potential parental sequences were CV-A2 (GenBank accession number: KX595284) and CV-A5 (GenBank accession number: KP289362). Further analyzing with SimPlot showed that the virus strain 2017FJFZ239 may recombine with CV-A2 strain (GenBank accession number: KX595284) in non-structural protein 2B, 2C and P3 regions.Conclusions:From 2011 to 2020, HFMD related CV-A5 in Fujian province belongs to E1 subgenotype, and there is a recombinant strain.
7.Efficacy of acellular dermis matrix combined with cervical strap muscle as a composite tissue flap for the treatment of laryngeal cancer
Yu LIN ; Wenxiang GAO ; Wenbin LEI ; Weiping WEN ; Xiaolin ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(12):1131-1136
Objective:To investigate the clinical efficacy of acellular dermis matrix combined with cervical strap muscle (ADM-CSM) as a composite tissue flap for repairing the laryngeal defect after partial laryngectomy.Methods:The medical records of 33 patients with laryngeal cancer who were diagnosed and treated at the First Affiliated Hospital of Sun Yat-sen University from January 2014 to December 2016 were retrospectively reviewed. The patients consisted of 32 males and 1 female with age range from 39 to 76 years. Laryngeal defects were repaired with ADM-CSM in 14 patients (2 for supraglottic laryngeal cancer, 12 for glottic laryngeal cancer) and with CSM fascial flaps in 19 patients (3 for supraglottic laryngeal cancer, 16 for glottic laryngeal cancer). Kaplan-Meier method was used to calculate the 3-year overall survival and local control rate. The functions of voice and swallowing after operation were evaluated by voice handicap index-30 (VHI-30) and MD Anderson dysphagia inventory. Univariate logistic regression analysis, t-test, and Mann-Whitney U test were used to compare the variables between the two groups. Results:The incidence of laryngeal stenosis was 2/14 in ADM-CSM group and 4/19 in CSM group. In the ADM-CSM group, 3-year overall survival and local control rates were 92.9% and 85.7%, respectively. In the CSM group, 3-year overall survival and local control rates were 78.9% and 84.2%, respectively. The time of operation(3 h vs. 4 h, Z=193.5, P<0.05), time of retaining the feeding tube(14 d vs. 17 d, Z=206.0, P<0.05), and length of stay(18.5 d vs. 22.1 d, t=-2.62, P<0.05) in the ADM-CSM group were significantly less than those in the CSM group. The quality of voice in the CSM group was better than that in the ADM-CSM group (66.85±27.65 vs.45.80±23.19, t=2.19, P<0.05), while swallowing function in the ADM-CSM group was better than that in the ACSM group (80.00[60.00, 80.00] vs.60.00[40.00, 80.00], Z=48.0, P<0.05). Conclusion:ADM-CSM is user-friendly control and safe composite tissue flap for repairing the laryngeal defect after partial laryngectomy, with less scar hyperplasia and higher satisfaction of swallowing function after operation.
8.Epidemiology and genetic characteristics of EV71 in Fujian Province,China
Wenxiang HE ; Yongjun ZHANG ; Guangmin CHEN ; Ying ZHU ; Wei CHEN ; Yuwei WENG
Chinese Journal of Zoonoses 2017;33(2):136-142
For investigating the epidemiology and genetic characteristics of enterovirus 71 (EV71) in Fujian from 2010 to 2015,we analyzed the surveillance data of EV71 and sequenced VP1 genes of 72 EV71 strains randomly picked from the past 6 years.The overall infection rate was gradually down and one incidence peak (from May to July) was observed each year.Major infectious population were focused on Xiamen,Fuzhou,Nanping and Quanzhou,the ages ranged from one to three years old.Scattered children were the most infected ones.The proportion of EV71 in the severe case was higher than in the HMFD(χ2 =732.064 5,P<0.000 1).EV71 circulated from 2010 to 2015 in Fujian Province was belonged to subgenotype C4a in consistent with vaccine strain (H07).Compared with the VP1 of vaccine strains,the divergence of complete VP1 nucleotide sequence was gradually expanding as time distance increased,but the sequence of amino acid was not found obvious difference.Variations in 4 key immune epitopes of amino acid had not appeared a regular pattern in year and not consistent with the trend of proportion of EV71 in HMFD.As a result,we considered the epidemiology characteristics of EV71 in Fujian was obvious,72 strains still belonged to C4a subgenotype and had no outstanding antigenic drift or mutation.Extensive epidemiology surveillance and genetic characteristic are needed for the application of EV71 vaccine.
9.Complete genome analysis of influenza A(H1N1) pdm09 virus isolated from one case of pneumonia of unknown etiology (PUE) in Fujian Province, China
Yanhua ZHANG ; Yuwei WENG ; Jianming ZHANG ; Wenqiong XIU ; Hongbin CHEN ; Lin ZHAO ; Wenxiang HE ; Ying ZHU ; Jianfeng XIE ; Kuicheng ZHENG
Chinese Journal of Zoonoses 2017;33(3):228-235
To study the biological characteristics and mutations of influenza A(H1N1)pdm09 virus isolated from one case of pneumonia of unknown etiology (PUE),which would provide references for clinical treatment and disease control,the throat swab specimen from the PUE case was isolated in the Madin-Darby Canine Kidney (MDCK) cells,and then the antigenicity,pathogenicity and drug resistance of influenza A (H1N1) pdm09 virus were analyzed after sequencing.As a result,one influenza virus strain was isolated from the specimen and named as A/FujianGulou/SWL64/2016(H1N1).The similarities of nucleotide sequences and amino acids sequences compared with the vaccine strain A/California/07/2009 (H1N1) were 96.9%-98.9% and 96.7%-99.5%,respectively.Eighteen amino acids had mutated in the HA and 4 mutations,K163Q,S185T,S203T and D222N,were involved in 3 different epitopes,which indicated that the antigenic drift had occurred in the influenza virus.The D222N mutation associated with receptor binding site made the virus infect lower respiratory tract more easily.The virus was still amantadine-resistance and oseltamivir-sensitive.In conclusion,the influenza A (H1N1) pdm09 virus in this study have occurred antigenic drift and has the molecular characterization of causing severe pneumonia,so further surveillance should be performed to prevent and control the influenza epidemic.
10.Prediction of clinical efficacy of breast cancer neoadjuvant chemotherapy using ultrasound-guided diffuse optical tomography
Wenxiang ZHI ; Cai CHANG ; Yi GAO ; Min CHEN ; Yaling CHEN ; Zhaoting SHI ; Aiyu MIAO ; Fen WANG ; Xiaoli ZHU
Chinese Journal of Ultrasonography 2017;26(4):325-329
Objective To investigate the value of ultrasound-guided diffuse optical tomography (US-guided DOT) to predict clinical efficacy of breast cancer neoadjuvant chemotherapy (NAC).Methods Eighty-eight breast cancer patients with 93 lesions were included.Pre-and post-last chemotherapy,the size,total hemoglobin concentration (THC) of each lesion were measured by ultrasonography (US) and US-guided DOT.Based on the guidelines to evaluate the response to treatment in solid tumors,the lesions of treated breast cancer patients were divided into 4 types of responses to NAC:complete response (CR),partial response (PR),stable disease (SD),and progressive disease (PD).Efficient groups include CR and PR groups.Results As expected,no significant difference was found in size and THC for untreated lesions (all P >0.05).However,for the treated lesions(P =0.001),THC,pre-vs post-treatment size changes (△Size%) (P =0.002) and THC changes (△THC%) (P <0.001) were significantly varied among CR,PR,SD,PD groups.When compared with pre-treated,tumor sizes after treatment were changed significantly in all CR(P <0.001),PR(P <0.001),SD (P =0.023) and PD (P =0.001),while significant change of THC was only found in CR(P <0.001),PR(P <0.001) and SD (P =0.002).When △THC% =23.9% as the threshold for prediction of NAC efficiency,the area under the curve of ROC was 0.75,and the sensitivity was 73.7%,specificity was 76.5 %,positive predictive value was 93.3 %,negative predictive value was 39.4%,accuracy was 74.2%.Conclusions △size% changes in consistent with △THC% among the intergroups,but their changes levels are different,the highest change percent appears in CR,gradually decreased in PR,SD groups.△THC% will contribute to predict preoperative clinical NAC efficacy.


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