1.The role and prognostic value of matrix metalloproteinase 19 in colorectal cancer and its liver metastasis
The Journal of Practical Medicine 2025;41(13):1987-1996
Objective To explore the function and molecular mechanisms of matrix metalloproteinase 19(MMP-19)in colorectal cancer(CRC)and liver metastasis of CRC(CRLM).Methods This study comprehen-sively analyzed transcriptomic data,single-cell data,and clinical information of CRC and CRLM patients retrieved from public databases,namely The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO).RNA sequencing analysis was carried out to identify biological functions associated with MMP-19 expression.The differ-ential expression of MMP-19 between primary lesions and liver metastatic lesions was evaluated using quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.In vitro functional assays were performed to validate the impact of MMP-19 on the proliferation,invasion,and migration of colorectal cancer cells.Results MMP-19 was highly expressed in CRC tissues and was significantly correlated with poor prognosis in both CRC and CRLM patients.Sequencing results and functional enrichment analysis demonstrated that MMP-19 is involved in epithelial-mesenchymal transition,amino acid and protein transport,cell proliferation,extracellular matrix organization,and the mitogen-activated protein kinase(MAPK)signaling pathway.Single-cell analysis revealed that the expression of MMP-19 in macrophages and dendritic cells was higher in both CRC primary tumors and liver metastases compared to normal tissues.In vitro experiments confirmed that MMP-19 enhances the proliferation,invasion,and migration capabilities of colorectal cancer cells.Conclusion MMP-19 has been shown to play a crucial role in promoting the development and progression of CRC.It increases the risk of postoperative recurrence and liver metastasis through inducing epithelial-mesenchymal transition and remodeling the immune microenvironment.Given these findings,MMP-19 emerges as a promising novel target for the diagnosis and treatment of both CRC and CRLM.
2.The role and prognostic value of matrix metalloproteinase 19 in colorectal cancer and its liver metastasis
The Journal of Practical Medicine 2025;41(13):1987-1996
Objective To explore the function and molecular mechanisms of matrix metalloproteinase 19(MMP-19)in colorectal cancer(CRC)and liver metastasis of CRC(CRLM).Methods This study comprehen-sively analyzed transcriptomic data,single-cell data,and clinical information of CRC and CRLM patients retrieved from public databases,namely The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO).RNA sequencing analysis was carried out to identify biological functions associated with MMP-19 expression.The differ-ential expression of MMP-19 between primary lesions and liver metastatic lesions was evaluated using quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.In vitro functional assays were performed to validate the impact of MMP-19 on the proliferation,invasion,and migration of colorectal cancer cells.Results MMP-19 was highly expressed in CRC tissues and was significantly correlated with poor prognosis in both CRC and CRLM patients.Sequencing results and functional enrichment analysis demonstrated that MMP-19 is involved in epithelial-mesenchymal transition,amino acid and protein transport,cell proliferation,extracellular matrix organization,and the mitogen-activated protein kinase(MAPK)signaling pathway.Single-cell analysis revealed that the expression of MMP-19 in macrophages and dendritic cells was higher in both CRC primary tumors and liver metastases compared to normal tissues.In vitro experiments confirmed that MMP-19 enhances the proliferation,invasion,and migration capabilities of colorectal cancer cells.Conclusion MMP-19 has been shown to play a crucial role in promoting the development and progression of CRC.It increases the risk of postoperative recurrence and liver metastasis through inducing epithelial-mesenchymal transition and remodeling the immune microenvironment.Given these findings,MMP-19 emerges as a promising novel target for the diagnosis and treatment of both CRC and CRLM.
3.Effects of Morinda officinalis oligosaccharides exposure during lactation on the Sprague-Dawley maternal rats and their offspring's development
Manman ZHAO ; Runcheng HE ; Ying YANG ; Zeping ZUO ; Xinyao CAO ; Chao WANG ; Nie WEN ; Sanlong WANG ; Xingchao GENG ; Zhibin WANG ; Xiaobing ZHOU
Adverse Drug Reactions Journal 2024;26(9):543-550
Objective:To explore the effects of maternal exposure to Morinda officinalis oligosaccharides (MOO) during lactation on the Sprague-Dawley (SD) maternal rats and their offspring's growth and development. Methods:Seventy-two female rats with a surviving litter size of ≥ 6 were divided into the excipients control group, MOO low-dose group (50 mg/kg), MOO medium-dose group (160 mg/kg), and MOO high-dose group (500 mg/kg) using a snake-shaped grouping based on body weight, with 18 rats per group. The rats were gavage fed once daily until 20 days of delivery. The response of maternal rats after MOO exposure during lactation, as well as the appearance, response, gross anatomical abnormalities of their F1 and F2 offspring were observed. The body weight and food intake of maternal rats during lactation and those of their offspring before and after weaning were measured. The behavior (central nervous system function) of the F1 and F2 offspring was evaluated using functional observation battery (FOB). The learning and memory function of the F1 offspring was evaluated using Y-maze test. The male and female F1 offspring in the same dose group were mated when they were raised to 10-12 weeks in order to observe the reproductive function of F1 female rats.Results:Compared with the excipients control group, no abnormality was found in the clinical observation of maternal rats in the 3 MOO exposure groups during lactation, and there was no significant differences in their body weight and daily food intake during lactation (all P>0.05). No significant effects were found on the appearance, clinical symptoms, gross anatomy, body weight, and food intake of the F1 and F2 offspring after maternal rats receiving MOO exposure during lactation. In the FOB of the F1 and F2 offspring and the Y-maze test of F1 offspring, few differences in MOO exposure groups were observed and lack of significant dose-response relationship. After pregnancy, there were no statistically significant differences in the number of corpus luteum, implantation number, birth index, delivery index, survival index, and weaning index in F1 female offspring of maternal rats exposed to MOO at different doses during lactation compared with those of the excipients control group (all P>0.05). Conclusions:There were no obvious toxic reactions in maternal rats after exposure to different doses of MOO during lactation, nor in the growth and development, nervous system, learning and memory, and reproductive function of their offspring.
4.Effects of Morinda officinalis oligosaccharides exposure during lactation on the Sprague-Dawley maternal rats and their offspring's development
Manman ZHAO ; Runcheng HE ; Ying YANG ; Zeping ZUO ; Xinyao CAO ; Chao WANG ; Nie WEN ; Sanlong WANG ; Xingchao GENG ; Zhibin WANG ; Xiaobing ZHOU
Adverse Drug Reactions Journal 2024;26(9):543-550
Objective:To explore the effects of maternal exposure to Morinda officinalis oligosaccharides (MOO) during lactation on the Sprague-Dawley (SD) maternal rats and their offspring's growth and development. Methods:Seventy-two female rats with a surviving litter size of ≥ 6 were divided into the excipients control group, MOO low-dose group (50 mg/kg), MOO medium-dose group (160 mg/kg), and MOO high-dose group (500 mg/kg) using a snake-shaped grouping based on body weight, with 18 rats per group. The rats were gavage fed once daily until 20 days of delivery. The response of maternal rats after MOO exposure during lactation, as well as the appearance, response, gross anatomical abnormalities of their F1 and F2 offspring were observed. The body weight and food intake of maternal rats during lactation and those of their offspring before and after weaning were measured. The behavior (central nervous system function) of the F1 and F2 offspring was evaluated using functional observation battery (FOB). The learning and memory function of the F1 offspring was evaluated using Y-maze test. The male and female F1 offspring in the same dose group were mated when they were raised to 10-12 weeks in order to observe the reproductive function of F1 female rats.Results:Compared with the excipients control group, no abnormality was found in the clinical observation of maternal rats in the 3 MOO exposure groups during lactation, and there was no significant differences in their body weight and daily food intake during lactation (all P>0.05). No significant effects were found on the appearance, clinical symptoms, gross anatomy, body weight, and food intake of the F1 and F2 offspring after maternal rats receiving MOO exposure during lactation. In the FOB of the F1 and F2 offspring and the Y-maze test of F1 offspring, few differences in MOO exposure groups were observed and lack of significant dose-response relationship. After pregnancy, there were no statistically significant differences in the number of corpus luteum, implantation number, birth index, delivery index, survival index, and weaning index in F1 female offspring of maternal rats exposed to MOO at different doses during lactation compared with those of the excipients control group (all P>0.05). Conclusions:There were no obvious toxic reactions in maternal rats after exposure to different doses of MOO during lactation, nor in the growth and development, nervous system, learning and memory, and reproductive function of their offspring.
5.Association between cord blood BPDE-DNA and neurodevelopment of children aged 0 and 2 years: A birth cohort study
Lijie WANG ; Huimin WANG ; Yaqing MENG ; Yuling HE ; Hongwei WANG ; Zeping REN ; Jisheng NIE ; Deliang TANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(6):412-418
Objective:To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development.Methods:In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old.Results:The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points.Conclusion:Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.
6.Association between cord blood BPDE-DNA and neurodevelopment of children aged 0 and 2 years: A birth cohort study
Lijie WANG ; Huimin WANG ; Yaqing MENG ; Yuling HE ; Hongwei WANG ; Zeping REN ; Jisheng NIE ; Deliang TANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(6):412-418
Objective:To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development.Methods:In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old.Results:The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points.Conclusion:Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.
7.Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway.
Yuchen PAN ; Zeping JIANG ; Dingya SUN ; Zhenghao LI ; Yingyan PU ; Dan WANG ; Aijun HUANG ; Cheng HE ; Li CAO
Neuroscience Bulletin 2019;35(5):802-814
The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.
8.Validity and reliability of the Chinese version of the Eating Disorder Examination Questionnaire 6.0 in female patients with eating disorders
Lian GU ; Jue CHEN ; Yue HUANG ; Qing KANG ; Jiabin HUANG ; Yanling HE ; Zeping XIAO
Chinese Mental Health Journal 2017;31(5):350-355
Objective:To evaluate the validity and reliability of the Chinese version of the Eating Disorder Examination Questionnaire 6.0 (EDE-Q 6.0) in female patients with eating disorders.Methods:A total of 239 patients with eating disorder and 142 healthy controls who were recruited consented to participate in the study and completed Chinese EDE-Q 6.0.Confirmatory factor analysis was used in patients to compare the original 4-factor model,1-factor model and 3-factor model.The criterion validity was tested with the Eating Disorder Inventory (EDI).Mann-Whitney U analysis was used to compare the differences of EDE-Q 6.0 scores on the two samples to test the empirical validity,and ROC analysis was used to determine the cut-off value.The internal consistency of the scale was tested in two samples.Among all participants,89 patients and 31 healthy controls were retested 1 month later.Results:The original 4-factor model fit better than the other two.The EDE-Q 6.0 total score and the EDI total score had a high consistency in the total sample,patients and controls,respectively (ICC =0.88,0.87,0.73).Patients had higher scores on the EDE-Q 6.0 than controls (Ps <0.01).The mean area under the curve (AUC) of EDE-Q 6.0 was 0.91,the optimal cut-off point of EDE-Q 6.0 was total score ≥ 1.27,sensitivity and specificity were 79.4% and 88.2% respectively.The Cronbach α coefficients were 0.95,0.91,and 0.88 for the total sample,patients and controls respectively.The test-retest reliabilities were 0.73 for the total scale,0.58,0.68,0.69 and 0.71 for the 4 factors.Conclusion:The Chinese version of the Eating Disorder Examination Questionnaire 6.0 have good psychometric properties and diagnosis accuracy,and it could be used to assess the severity of clinical symptoms.
9.Validity, reliability, and acceptability of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population
Wenjuan WANG ; Jing DONG ; Zeping REN ; Bo CHEN ; Wei HE ; Weidong LI ; Zuowen HAO
Chinese Journal of Preventive Medicine 2016;50(7):584-588
Objective To evaluate the validity, reliability, and acceptability of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population (HILKAB), and provide scientific evidence for its usage. Methods By convenient sampling, we selected 406 individuals at high risk for diabetes for survey using the HILKAB. Pearson correlation coefficient, factor analysis, independent sampling, and t-test for high-and low-score groups were used to evaluate the content validity, construct validity, and discriminant validity of the scale. Reliability of the scale was evaluated by internal consistency, which included Cronbach'sαcoefficient,θcoefficient,Ωcoefficient, and split-half reliability. Scale acceptability was evaluated by acceptance rate and completion time of the survey. Results In this study, 366 questionnaires (90.1%) was qnalified and the completion time was (8.62 ± 2.79) minutes. Scores for knowledge, attitude, and behavior were 10.60±3.73, 26.56±3.58, 17.09±9.74, respectively. The scale had good face validity and content validity. The correlation coefficient of items and the dimension to which they belong was between 0.25 and 0.97, and the correlation coefficient of three dimensions and the entire scale was between 0.64 and 0.91, all with P<0.001. Factor analysis of the scale extracted eight common factors. The cumulative variance contribution rate was 65.23%, thereby reaching the 50% approved standard. Of 30 items there were 29 items with factor loadings ≥0.40, indicating the scale had good construct validity. For the high-score group, scores for knowledge, attitude, and behavior dimensions were 13.89±2.55, 29.56± 2.46, 28.05 ± 2.93, respectively, which were higher than those for the low-score group (7.67 ± 2.78, 23.89 ± 3.35, 6.25 ± 3.13); t-values were 55.14, 119.40, 95.29, respectively, with P<0.001. The scale consisted of three dimensions: knowledge, attitude, and behavior. The Cronbach's α coefficient was between 0.84 and 0.92, the θ coefficient was between 0.85 and 0.96, the Ω coefficient was between 0.90 and 0.94, and the split-half reliability was between 0.77 and 0.95, reaching the 0.70 standard letter. Conclusion The validity, reliability, and acceptability of the HILKAB scale were satisfactory for use in a population at high risk of diabetes.
10.Validity, reliability, and acceptability of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population
Wenjuan WANG ; Jing DONG ; Zeping REN ; Bo CHEN ; Wei HE ; Weidong LI ; Zuowen HAO
Chinese Journal of Preventive Medicine 2016;50(7):584-588
Objective To evaluate the validity, reliability, and acceptability of the scale of knowledge, attitude, and behavior of lifestyle intervention in a diabetes high-risk population (HILKAB), and provide scientific evidence for its usage. Methods By convenient sampling, we selected 406 individuals at high risk for diabetes for survey using the HILKAB. Pearson correlation coefficient, factor analysis, independent sampling, and t-test for high-and low-score groups were used to evaluate the content validity, construct validity, and discriminant validity of the scale. Reliability of the scale was evaluated by internal consistency, which included Cronbach'sαcoefficient,θcoefficient,Ωcoefficient, and split-half reliability. Scale acceptability was evaluated by acceptance rate and completion time of the survey. Results In this study, 366 questionnaires (90.1%) was qnalified and the completion time was (8.62 ± 2.79) minutes. Scores for knowledge, attitude, and behavior were 10.60±3.73, 26.56±3.58, 17.09±9.74, respectively. The scale had good face validity and content validity. The correlation coefficient of items and the dimension to which they belong was between 0.25 and 0.97, and the correlation coefficient of three dimensions and the entire scale was between 0.64 and 0.91, all with P<0.001. Factor analysis of the scale extracted eight common factors. The cumulative variance contribution rate was 65.23%, thereby reaching the 50% approved standard. Of 30 items there were 29 items with factor loadings ≥0.40, indicating the scale had good construct validity. For the high-score group, scores for knowledge, attitude, and behavior dimensions were 13.89±2.55, 29.56± 2.46, 28.05 ± 2.93, respectively, which were higher than those for the low-score group (7.67 ± 2.78, 23.89 ± 3.35, 6.25 ± 3.13); t-values were 55.14, 119.40, 95.29, respectively, with P<0.001. The scale consisted of three dimensions: knowledge, attitude, and behavior. The Cronbach's α coefficient was between 0.84 and 0.92, the θ coefficient was between 0.85 and 0.96, the Ω coefficient was between 0.90 and 0.94, and the split-half reliability was between 0.77 and 0.95, reaching the 0.70 standard letter. Conclusion The validity, reliability, and acceptability of the HILKAB scale were satisfactory for use in a population at high risk of diabetes.

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