Objective To investigate the association between the rs3918242 polymorphism in the matrix metalloproteinase-9(MMP-9)gene and the risk of simplerenal cysts(SRCs)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 483 outpatient with T2DM and inpatient with T2DM admitted to endocrinology department in our hospital were enrolledin this study from June 2020 to December 2023.All the patients were divided into two groups according to the diagnostic criteria for SRCs:T2DM group(n=355)and T2DM with SRCs group(SRCs,n=128).General clinical characteristics and biochemical indicators were compared between the two groups.The correlation between rs3918242 polymorphism and T2DM with SRCs was analyzed by spearman correlation.LASSO regression and stepwise linear regression were employed to identify factors influencing T2DM with SRCs.Multivariate logistic regression analysis was performed to determine the independent risk factors for SRCsin patients with T2DM.Results Serum MMP-9 level was higher in SRCs group than in T2DM group(P<0.05).The frequency of the rs3918242 CT/TT genotypes and T allele was significantly higher in SRCs group than in T2DM group(P<0.05).Spearman correlation analysis demonstrateda positive correlation betweenthers3918242 genotype CT/TT and the presence of SRCs(r=0.344,0.150,P<0.05)and between the T allele frequency and SRCs(r=0.355,P=0.000)in patients with T2DM.Stepwise linear regression identified age,fasting plasma glucose,serum creatinine,albumin,platelet count,estimated glomerular filtration rate(eGFR),calcium levels,MMP-9,and rs3918242 CT/TT genotype as influencing factors for SRCs in T2DM patients.Logistic regression analysis revealed that FPG,albumin,eGFR,Scr,MMP-9,and the rs3918242 CT/TT genotype were independent risk factors for SRCs in patients with T2DM.Conclusions Serum MMP-9 levels areelevatedin T2DM patients with SRCs,and rs3918242 CT/TT genotype in MMP-9 gene areat increased risk for developing SRCs.

Objective Bladder cancer(BLCA)is a common disease,and the pathogenesis of which is not clear.This study aims to find the key genes of bladder cancer for future prevention and treatment.Methods The bladder cancer dataset GSE121711 was obtained from the Gene Expression Omnibus(GEO)database of NCBI.The weighted gene coexpression network analysis(WGCNA)was performed on GEO data to identify the gene modules highly associated with BLCA in the samples.The intersecting genes of differentially expressed genes(DEG)and genes in the module were extracted.The common genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedi-a of Genes and Genomes(KEGG),and the key genes with the highest degree were further screened through the Protein-protein interac-tion(PPI)network.The cluster analysis is carried out.Finally,the LASSO is used to establish the diagnostic model.The expression of hub genes in BLCA tissues and normal tissues was detected by using reverse transcription real-time quantitative polymerase chain reaction(RT-qPCR).Results WGCNA showed the most significant association between the black module and bladder cancer.There were 611 genes in the black module and intersected with DEG for 449 common genes.A diagnostic model consisting of RAC3,APOL4,FASN and CLASRP was constructed using LASSO,and analysis was conducted using receiver operating characteristic(ROC)curves at time points of 365 days(1 year),1095 days(3 years)and 1825 days(5 years).The Area Under Curve(AUC)of 365(1 year),1095(3 years)and 1825(5 years)were 80％,82％and 85％,respectively.The results were verified on the combined dataset of GSE101723 and GSE83586,which were found to be similar to those of bioinformatics.The relative expression levels of hub genes RAC3,APOL4,FASN and CLASRP mRNA in BLCA tissues were significantly higher than those in normal tissues(t=8.074,P＜0.0001;t=3.577,P＜0.001;t=12.241,P＜0.0001;t=8.846,P＜0.0001).Conclusion We constructed a BLCA diagnostic model and found that RAC3,APOL4,FASN and CLASRP were potential biomarkers that may provide new insights to improve the early diagnosis and treatment of blad-der cancer.

Objective To investigate the association between the rs3918242 polymorphism in the matrix metalloproteinase-9(MMP-9)gene and the risk of simplerenal cysts(SRCs)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 483 outpatient with T2DM and inpatient with T2DM admitted to endocrinology department in our hospital were enrolledin this study from June 2020 to December 2023.All the patients were divided into two groups according to the diagnostic criteria for SRCs:T2DM group(n=355)and T2DM with SRCs group(SRCs,n=128).General clinical characteristics and biochemical indicators were compared between the two groups.The correlation between rs3918242 polymorphism and T2DM with SRCs was analyzed by spearman correlation.LASSO regression and stepwise linear regression were employed to identify factors influencing T2DM with SRCs.Multivariate logistic regression analysis was performed to determine the independent risk factors for SRCsin patients with T2DM.Results Serum MMP-9 level was higher in SRCs group than in T2DM group(P<0.05).The frequency of the rs3918242 CT/TT genotypes and T allele was significantly higher in SRCs group than in T2DM group(P<0.05).Spearman correlation analysis demonstrateda positive correlation betweenthers3918242 genotype CT/TT and the presence of SRCs(r=0.344,0.150,P<0.05)and between the T allele frequency and SRCs(r=0.355,P=0.000)in patients with T2DM.Stepwise linear regression identified age,fasting plasma glucose,serum creatinine,albumin,platelet count,estimated glomerular filtration rate(eGFR),calcium levels,MMP-9,and rs3918242 CT/TT genotype as influencing factors for SRCs in T2DM patients.Logistic regression analysis revealed that FPG,albumin,eGFR,Scr,MMP-9,and the rs3918242 CT/TT genotype were independent risk factors for SRCs in patients with T2DM.Conclusions Serum MMP-9 levels areelevatedin T2DM patients with SRCs,and rs3918242 CT/TT genotype in MMP-9 gene areat increased risk for developing SRCs.

Objective Bladder cancer(BLCA)is a common disease,and the pathogenesis of which is not clear.This study aims to find the key genes of bladder cancer for future prevention and treatment.Methods The bladder cancer dataset GSE121711 was obtained from the Gene Expression Omnibus(GEO)database of NCBI.The weighted gene coexpression network analysis(WGCNA)was performed on GEO data to identify the gene modules highly associated with BLCA in the samples.The intersecting genes of differentially expressed genes(DEG)and genes in the module were extracted.The common genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedi-a of Genes and Genomes(KEGG),and the key genes with the highest degree were further screened through the Protein-protein interac-tion(PPI)network.The cluster analysis is carried out.Finally,the LASSO is used to establish the diagnostic model.The expression of hub genes in BLCA tissues and normal tissues was detected by using reverse transcription real-time quantitative polymerase chain reaction(RT-qPCR).Results WGCNA showed the most significant association between the black module and bladder cancer.There were 611 genes in the black module and intersected with DEG for 449 common genes.A diagnostic model consisting of RAC3,APOL4,FASN and CLASRP was constructed using LASSO,and analysis was conducted using receiver operating characteristic(ROC)curves at time points of 365 days(1 year),1095 days(3 years)and 1825 days(5 years).The Area Under Curve(AUC)of 365(1 year),1095(3 years)and 1825(5 years)were 80％,82％and 85％,respectively.The results were verified on the combined dataset of GSE101723 and GSE83586,which were found to be similar to those of bioinformatics.The relative expression levels of hub genes RAC3,APOL4,FASN and CLASRP mRNA in BLCA tissues were significantly higher than those in normal tissues(t=8.074,P＜0.0001;t=3.577,P＜0.001;t=12.241,P＜0.0001;t=8.846,P＜0.0001).Conclusion We constructed a BLCA diagnostic model and found that RAC3,APOL4,FASN and CLASRP were potential biomarkers that may provide new insights to improve the early diagnosis and treatment of blad-der cancer.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective:To investigate the effects of Wnt5a on the vasculogenic mimicry(VM)and cancer stem cell(CSC)properties of prostate cancer(PCa)cells by upregulating the expression of miR-141-3p.Methods:Human prostate epithelial cell line RWPE-1 and PCa cell lines PC-3,LNCaP,and DU145 were cultured.qPCR was employed to detect miR-141-3p expression,and Western blotting(WB)was used to measure Wnt5a protein levels.Stable Wnt5a-knockdown or miR-141-3p-knockdown LNCaP and DU145 cell lines were established respectively via plasmid transfection.VM formation ability was assessed by three-dimensional culture assay.Cell proliferation ability and drug sensitivity were measured by CCK-8 assay.Cell migration and invasion abilities were detected using wound healing and Transwell assays,respectively.The expressions of VM-related molecules and CSC markers were detected by qPCR and WB.Colony formation ability was determined by clonogenic assay.The proportion of CD133+cells was sorted and calculated by flow cytometry.The expressions of miR-141-3p and Wnt5a in CD133+and CD133-cells were detected by qPCR and WB.Stable Wnt5a-overexpressing PCa cell lines were constructed via plasmid transfection.The effects of Wnt5a and different Wnt pathway downstream inhibitors on miR-141-3p expression and promoter activity were detected by qPCR and dual-luciferase reporter assays.Expression of c-Jun was knocked down in Wnt5a-overexpressing cells using si-c-Jun transfection.The target binding relationship between c-Jun and the miR-141-3p promoter was verified by qPCR,dual-luciferase reporter assay,and chromatin immunoprecipitation assay.Results:The expressions of miR-141-3p and Wnt5a were significantly higher in PCa cells compared with those in RWPE-1 cells,with the highest relative expression in DU145 cells and the lowest in LNCaP cells(P<0.001).Downregulation of Wnt5a or miR-141-3p significantly inhibited VM formation ability and stemness of PCa cells,and significantly suppressed the proliferation,migration,invasion abilities,and enhanced the sensitivity to bicalutamide of PCa cells(P<0.05 or P<0.01 or P<0.001).Downregulation of Wnt5a significantly inhibited miR-141-3p expression and promoter transcriptional activity(P<0.01 or P<0.05),whereas upregulation of Wnt5a significantly promoted miR-141-3p expression and promoter transcriptional activity(P<0.01 or P<0.001).The promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity could be inhibited by a JNK/c-Jun pathway inhibitor(P>0.05).Downregulation of c-Jun significantly inhibited the promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity(P>0.05).c-Jun could bind to the-348 to-295 sequence of the miR-141-3p promoter.In absence of this fragment Wnt5a wouldn't promote miR-141-3p expression(P>0.05).Conclusion:The Wnt5a/JNK/c-Jun signaling pathway can upregulate miR-141-3p expression,and thereby promote VM formation in PCa cells,possibly by activating CSC properties.

Objective To observe the correlations of quantitative 99Tcm-methoxyisobutylisonitrile(99Tcm-MIBI)SPECT/CT imaging parameters,functional markers and disease severity of primary hyperparathyroidism(PHPT)related to parathyroid adenoma.Methods Fifty-eight patients with PHPT due to single parathyroid adenoma were retrospectively collected,clinical data including serum parathyroid hormone(PTH)levels were recorded,and quantitative 99Tcm-MIBI SPECT/CT imaging parameters were obtained.According to serum calcium level reflecting disease severity(2.55-2.80 mmol/L or＞2.80 mmol/L),the patients were categorized into type Ⅰ group(n=25)and type Ⅱ group(n=33).Quantitative metabolic parameters of lesions,i.e.standard uptake value(SUV)values(the maximum SUV[SUVmax],the mean SUV[SUVmean],the peak SUV[SUVpeak]),SUV values normalized by lean body mass(SUL,including the maximum SUL[SULmax],the mean SUL[SULmean]and the peak SUL[SULpeak]),total lesion volume(TLV)and total lesion uptake(TLU),as well as derived parameters such as lesion to background ratio(LBR)contrast to contralateral deltoid muscle and lesion density(LD)were obtained from reconstructed images and compared between groups.The area under curves(AUC)of the receiver operating characteristic(ROC)curves were used to evaluate the performance of each index and their combined logistic regression model for distinguishing the severity of PHPT.Results The serum PTH and serum calcium levels in type Ⅰ group were both significantly lower than those in type Ⅱ group(both P＜0.05).No statistically significant difference of detection rate of parathyroid adenoma with PHPT was found between 99Tcm-MIBI SPECT/CT and planar imaging(96.56％vs.91.38％,P=0.063).TLV and TLU were weakly correlated with serum PTH(rs=0.416,0.422)and serum calcium levels(rs=0.391,0.349)(all P＜0.05).TLV and TLU values in type Ⅰgroup were significantly lower than those in type Ⅱ group(both P＜0.05).The AUC of PTH,TLV and TLU for differentiating type Ⅰ and type Ⅱ PHPT related to parathyroid adenoma was 0.770,0.741 and 0.716,respectively,of the combination of all the three was 0.790,and no statistical difference was detected(Z=0.361-1.454,all P＞0.05).Conclusion 99Tcm-MIBI SPECT/CT quantitative metabolic parameters TLV and TLU could be used to evaluate the functional status of parathyroid and severity of PHPT related to parathyroid adenoma.

Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.

Objective To observe the correlations of quantitative 99Tcm-methoxyisobutylisonitrile(99Tcm-MIBI)SPECT/CT imaging parameters,functional markers and disease severity of primary hyperparathyroidism(PHPT)related to parathyroid adenoma.Methods Fifty-eight patients with PHPT due to single parathyroid adenoma were retrospectively collected,clinical data including serum parathyroid hormone(PTH)levels were recorded,and quantitative 99Tcm-MIBI SPECT/CT imaging parameters were obtained.According to serum calcium level reflecting disease severity(2.55-2.80 mmol/L or＞2.80 mmol/L),the patients were categorized into type Ⅰ group(n=25)and type Ⅱ group(n=33).Quantitative metabolic parameters of lesions,i.e.standard uptake value(SUV)values(the maximum SUV[SUVmax],the mean SUV[SUVmean],the peak SUV[SUVpeak]),SUV values normalized by lean body mass(SUL,including the maximum SUL[SULmax],the mean SUL[SULmean]and the peak SUL[SULpeak]),total lesion volume(TLV)and total lesion uptake(TLU),as well as derived parameters such as lesion to background ratio(LBR)contrast to contralateral deltoid muscle and lesion density(LD)were obtained from reconstructed images and compared between groups.The area under curves(AUC)of the receiver operating characteristic(ROC)curves were used to evaluate the performance of each index and their combined logistic regression model for distinguishing the severity of PHPT.Results The serum PTH and serum calcium levels in type Ⅰ group were both significantly lower than those in type Ⅱ group(both P＜0.05).No statistically significant difference of detection rate of parathyroid adenoma with PHPT was found between 99Tcm-MIBI SPECT/CT and planar imaging(96.56％vs.91.38％,P=0.063).TLV and TLU were weakly correlated with serum PTH(rs=0.416,0.422)and serum calcium levels(rs=0.391,0.349)(all P＜0.05).TLV and TLU values in type Ⅰgroup were significantly lower than those in type Ⅱ group(both P＜0.05).The AUC of PTH,TLV and TLU for differentiating type Ⅰ and type Ⅱ PHPT related to parathyroid adenoma was 0.770,0.741 and 0.716,respectively,of the combination of all the three was 0.790,and no statistical difference was detected(Z=0.361-1.454,all P＞0.05).Conclusion 99Tcm-MIBI SPECT/CT quantitative metabolic parameters TLV and TLU could be used to evaluate the functional status of parathyroid and severity of PHPT related to parathyroid adenoma.

Objective:To investigate the perinatal outcome of selective fetal reduction of dizygotic twins pregnancies after double embryo transferred assisted by in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI). Methods:The clinical data of patients with single birth who underwent IVF/ICSI after double embryo transferred from September 1, 2005 to July 31, 2020 in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were retrospectively analyzed. The patients were divided into three groups according to the occurrence of fetal reduction: 80 cases of dizygotic twins to singleton by selective fetal reduction (group A), 832 cases of dizygotic twins to singleton by spontaneous fetal reduction (group B), and 6 178 cases of singleton (group C). Using group A as the reference, after approximately propensity score matching (PSM) with 1∶4 ratio, 289 cases in group B and 271 cases in group C were obtained. The differences in baseline data and perinatal outcomes between group A and group B or group C were analyzed.Results:1) Before PSM, there were statistically significant differences in patients' age, previous fertility history, type of infertility, and stage of embryo transferred between group A and group B or group C (all P<0.05); after PSM, there were no statistically significant differences in baseline data between group A and group B or group C (all P>0.05). 2) After PSM, the premature birth rate was higher in group A than in group B [17.5% (14/80) vs. 8.7% (25/289), P=0.023] and the gestational weeks [(38.18±1.98) weeks vs. (38.64±1.83) weeks, P=0.034] were lower; group A had higher incidence rates of premature birth [17.5% (14/80) vs. 7.7% (21/271), P=0.011] and premature rupture of membranes [5.0% (4/80) vs. 0.4% (1/271), P=0.002] than those in group C, but gestational weeks [(38.18±1.98) weeks vs. (38.85±1.47) weeks, P=0.002] and birth weight [(3 253.07±475.73) g vs. (3 384.89±479.54) g, P=0.029] were lower. Conclusion:Perinatal outcomes of selective fetal reduction of dizygotic twins pregnancies after assisted by IVF/ICSI were poor. Selective fetal reduction in multiple pregnancies is not the best remedy. The strategy of selective single embryo transfer should be adopted to effectively reduce the rate of multiple pregnancies and improve maternal and infant outcomes.