1.Essential roles of fibroblast growth factors in male reproduction
National Journal of Andrology 2024;30(1):3-8
The testis serves as the reproductive gland in male mammals,primarily tasked with the production of sperm and syn-thesis of androgens.A complex signaling network consisting of various cell types,including germ cells,Sertoli cells,and Leydig cells,supports the structure and maintains the function of the testis.Apart from the hypothalamic-pituitary-gonadal axis,various sex hormones and cytokines are also implicated in the regulation of testicular function.The fibroblast growth factor(FGF)represents a crucial class of active cytokines that stimulate cell proliferation,induce tissue differentiation,and govern organ development.This review summari-zes the molecular mechanisms of FGF regulating testicular development and spermatogenesis and maintaining male fertility.
2.Expression of the D930020B18Rik gene in the mouse testis during spermatogenesis:Characteristics and potential role
Yong WU ; Wen-Lin CHANG ; Yuan TIAN ; Ming YE ; Ya-Wei ZHANG ; Zeng ZHANG
National Journal of Andrology 2024;30(1):9-17
Objective:To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis.Methods:Using gene expression profile microarray,we identified highly ex-pressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR,immunohistochemistry,Western blot and immunofluorescence staining,and verified its function and molecular mechanism using bioinformatics analysis,dual-luciferase reporter assay and cell cycle synchronization.Results:The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks(PNW),increased from the 3rd PNW to sexual maturity,localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids,but was absent in the nuclei of mature sperm.Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals.Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation(normalized enrichment score[NES]=1.652,P<0.01,false discov-ery rate[FDR]=0.153),meiosis(NES=1.960,P<0.01,FDR=0.001)and formation of microtubule cytoskeleton during mitosis(NES=1.903,P<0.01,FDR=0.009).Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation.Conclusion:The D930020B18Rik gene is expressed in the mouse testis in a time-and location-specific manner,highly associated with spermiogenesis,mainly localized in the nuclei of germ cells,and may be involved in the meiosis of spermatocytes and spermiogenesis.
3.Expressions of zinc homeostasis proteins,GPR39 and ANO1 mRNA in the sperm of asthenozoospermia patients and their clinical significance
Chun HE ; Fang-Fang DAI ; Jun-Sheng LIU ; Ya-Song GENG ; Jun-Xia ZHOU ; Yi-Zhen HU ; Bo ZHENG ; Shu-Song WANG
National Journal of Andrology 2024;30(1):18-25
Objective:To explore the expressions of zinc homeostasis-related proteins,G protein-coupled receptor 39(GPR39)and ANO1 mRNA in the sperm of patients with asthenozoospermia(AS),and analyze their correlation with sperm motility.Methods:We collected semen samples from 82 male subjects with PR+NP<40%,PR<32%and sperm concentration>15 × 106/ml(the AS group,n=40)or PR+NP≥40%,PR≥32%and sperm concentration>15 × 106/ml(the normal control group,n=42).We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system,detected the expressions of zinc transporters(ZIP13,ZIP8 and ZNT10),metallothioneins(MT1G,MT1 and MTF),GPR39,and calcium-dependent chloride channel protein(ANO1)in the sperm by real-time quantitative PCR(RT qPCR),examined free zinc distribution in the sperm by laser confocal microscopy,and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining,followed by Spearman rank correlation analysis of their correlation with semen parameters.Results:There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups(P>0.05).Compared with the controls,the AS patients showed a significantly reduced free zinc level(P<0.05),relative expressions of MT1G,MTF,ZIP13,GPR39 and ANO1 mRNA(P<0.05),and that of the GPR39 protein in the AS group(P<0.05).No statistically significant differences were observed in the relative expression levels of ZIP8,ZNT10 and MT1 mRNA between the two groups(P>0.05).The relative expression levels of GPR39,ANO1,MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm(P<0.05).Conclusion:The expressions of zinc homeostasis proteins(MT1G,MTF and ZIP13),GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia pa-tients,and positively correlated with sperm motility.
4.Transperineal versus transrectal ultrasound-guided prostate biopsy in detection of clinically significant and insignificant prostate cancer:A prospective randomized controlled trial
Wei-Yong LIU ; Tao WANG ; Dan-Dan MA ; Peng WANG
National Journal of Andrology 2024;30(1):26-31
Objective:To compare transperineal prostate biopsy(TPB)with transrectal ultrasound-guided prostate biopsy(TRUSB)in detection of clinically significant prostate cancer(csPCa)and insignificant PCa(insPCa).Methods:We conducted a prospective randomized clinical study on 279 patients receiving TPB(n=144)or TRUSB(n=135)from January 2022 to January 2023,and compared the detection rates of csPCa and insPCa between the two groups.Results:The detection rate of PCa was signifi-cantly higher in the TPB than in the TRUSB group(37.50%vs 28.15%,P=0.026).There were no statistically significant differ-ences between the TPB and TRUSB groups in the detection rates of insPCa(6.94%[n=10]vs 4.45%[n=6],P>0.05)and csPCa(30.56%[n=44]vs 23.70%[n=32],P>0.05),nor in the detection rate of csPCa between different groups of age,PSA concentration and prostate volume(P>0.05).No statistically significant differences were observed between the TPB and TRUSB groups either in the positive rate of biopsy punctures([16.44±2.86]%vs[12.48±2.39]%,P>0.05)or in the bi-opsy-related complications of urinary retention,urinary tract infection,hematuria and rectal bleeding(P>0.05).Conclusion:TPB is more effective than TRUSB in detection of PCa,but there is no statistically significant difference between the two approaches in the detection rates of csPCa and insPCa.
5.Establishment of a predictive scoring model and preventive measures for bladder neck contracture after laparoscopic enucleation of the prostate with urethra preservation
Zu-Pan LI ; Jiang GU ; Yong-Chun ZHANG ; Qing-Tao YANG ; Miao LIU
National Journal of Andrology 2024;30(1):32-39
Objective:To establish a predictive scoring model for bladder neck contracture(BNC)after laparoscopic enuclea-tion of the prostate with preservation of the urethra(Madigan surgery)and explore the preventive measures against this postoperative complication.Methods:We included 362 cases of BPH treated by laparoscopic Madigan surgery from January 2019 to March 2022(45 with and 317 without postoperative BNC)in the training group and another 120 cases treated the same way in the verification group,collected the clinical data on the patients and evaluated the results of surgery.Using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression,we analyzed the risk factors for postoperative BNC and constructed a predictive scoring model for evaluation of the factors.Results:Compared with the baseline,the IPSS,quality of life(QOL)score and postvoid residual urine volume(PVR)were significantly decreased(P<0.05)while the maximum urinary flow rate(Qmax)remarkably in-creased(P<0.05)in the BPH patients at 3 months after surgery.Eight non-zero characteristic predictors were identified by LASSO regression analysis.Multivariate logistic regression analysis showed that short clinical experience of the surgeon,concurrent prostatitis,bladder rinse solution temperature<34℃,catheter blockage,urethral balloon injection volume>40 ml and postoperative constipation were independent risk factors for postoperative BNC(P<0.05).The best cut-off value was 2.36 points in both the training and the verification groups.The results of evaluation exhibited a high discriminability of the predictive scoring model.Conclusion:Laparo-scopic Madigan surgery is a safe and effective method for the treatment of BPH.Short clinical experience of the surgeon,concurrent prostatitis,bladder rinse solution temperature<34℃,catheter blockage,water injected into the urethral balloon>40 ml and postop-erative constipation were independent risk factors for postoperative BNC.The predictive scoring model constructed in this study has a good discriminability and is simple and feasible,contributive to the prediction of postoperative BNC in BPH patients undergoing laparo-scopic Madigan surgery.
6.Diagnosis and treatment of small-cell carcinoma of the prostate:A report of 2 cases
Long-Wei LU ; Xiu-Quan SHI ; Song XU ; Ding WU ; Lei WANG ; Dian FU ; Zhen-Yu XU
National Journal of Andrology 2024;30(1):40-43
Objective:To explore the clinical manifestations,diagnosis,pathological features and treatment of small-cell carci-noma of the prostate(SCCP).Methods:We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018,and reviewed relevant literature.Results:Both the patients had the symptoms of frequent,urgent and difficult urination,with an elevated level of PSA and grades Ⅱ-Ⅲ enlargement of the prostate at palpation.One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor.Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases.One of them was treated by eto-poside-platinum(EP)chemotherapy and died of systemic multiple organ failure 20 months after diagnosis,while the other underwent endocrine therapy and has lived with tumor up to the present day.Conclusion:The incidence rate of SCCP is low,its malignancy is high,and its prognosis is poor.The average survival of the patient is about 7 to 10 months after diagnosis.Currently there is no effec-tive management of the dissease,except by relying on the experience of the treatment of small-cell lung cancer,with chemotherapy as the main option.
7.Clinical and genetic characteristics of a case of primary ciliary dyskinesia caused by new frameshift mutation of the DNAH5 gene
Meng-Yang LI ; Shan HUANG ; Li-Na MA ; An-Cong WANG
National Journal of Andrology 2024;30(1):44-50
Objective:To investigate the clinical and genetic characteristics of a case of primary ciliary dyskinesia(PCD).Methods:We collected the clinical data on a case of PCD treated in the Department of Reproductive Medicine of Linyi People's Hospi-tal in July 2020,detected the genes of the patient by whole-exome sequencing(WES),verified the candidate mutations by Sanger se-quencing,and predicted the protein structure of the mutant gene by SWISS-MODEL.Results:The proband was found with the clini-cal phenotypes of chronic rhinitis,bronchiectasis,visceral transposition and male infertility.WES revealed a homozygous frameshift variation of c.12890dup(p.N4297Kfs*13)in exon 74 of the DNAH5 gene,which led to the premature termination of polypeptide chain synthesis and affected the gene function.SWISS-MODEL prediction showed that some of the amino acid residues were deleted af-ter mutation,resulting in a 3D conformational change of the protein.This variation was not recorded in the ClinVar,gnomAD and OMIM databases and,according to the relevant guidelines of the American College of Genetics and Genomics,was classified as a path-ogenic variation(PVS1+PM2_P+PM3_P).Conclusion:The homozygous variation of the DNAH5 gene c.12890dup(p.N4297Kfs*13)may be the cause of the clinical phenotype of this case of PCD,and the above findings have enriched the variation spectrum of the DNAH5 gene.
8.Potential action mechanism of Yishen Tongluo Prescription on male infertility:An analysis based on network pharmacology
Gao-Li HAO ; Zi-Xue SUN ; Li-Peng FAN ; Lei XU ; Guo-Zheng QIN
National Journal of Andrology 2024;30(1):51-59
Objective:To analyze the main active components and potential molecular mechanism of Yishen Tongluo Prescrip-tion(YTP)in the treatment of male infertility based on network pharmacological technology.Methods:We searched and sorted the main active components of YTP and their individual potential targets in the databases of Systematic Pharmacology of Traditional Chinese Medicine(TCM)and Bioinformatics Analysis Tool of the Molecular Mechanism of TCM,and screened the targets related to male infer-tility diseases in the databases of Genecards,DisGeNET and OMIM.We made a Venn diagram by intersecting the predicted targets of YTP and those of male infertility diseases,constructed visualized networks for the association of the intersection targets and protein-pro-tein interaction(PPI)using the Cytoscape software and STRING platform respectively,and conducted gene ontology(GO)and KEGG enrichment analyses using the DAVID database and R language"Cluster Profiler"software package respectively.Results:A total of 99 active components,250 targets of YTP,4 397 targets of male infertility and 127 common targets were identified.GO analysis re-vealed that the biological processes of the common targets mainly included transcriptional regulation of RNA polymerase promoter Ⅱ,regulation of gene expressions,regulation of apoptosis,responses to estrogen,and cell responses to hypoxia.KEGG analysis showed significant enrichment of the common targets in the estrogen signaling pathway,cell apoptosis pathway,AGE-RAGE signaling pathway in diabetic complications,and TNF signaling pathway.Conclusion:Through network pharmacology,we identified the main active components of YTP and its multi-target and multi-pathway mechanism in the treatment of male infertility,which has paved the ground for animal and cell experiments in verifying the action mechanism of YTP on male infertility.
9.Advances in artificial intelligence-assisted MRI radiomics in the diagnosis and treatment of prostate cancer
Zi-Chun LIANG ; Chao SUN ; Ming CHEN
National Journal of Andrology 2024;30(1):60-65
Prostate cancer(PCa)is the second most common cancer worldwide and the fifth leading cause of cancer deaths in men.Magnetic resonance imaging(MRI),with its high sensitivity and specificity in detecting PCa,is currently the most widely used imaging technique for tumor localization and staging.MRI plays a significant role in risk stratification of patients with neoplasm,sur-veillance of low-risk patients,and monitoring of recurrence after treatment.Radiomics is an emerging and promising tool that allows quantitative assessment of tumors in images by converting digital images into mineable high-dimensional data.Imaging histology aims to increase the number of features that can be used to detect PCa,avoid unnecessary biopsies,determine tumor aggressiveness and moni-tor recurrence after treatment.Artificial intelligence integration of imaging histology data,including those of different imaging modalities(e.g.,PET-CT)as well as other clinical and histopathological data,can improve the prediction of tumor aggressiveness and guide clinical decision-making and patient management.The aim of this review is to present current research applications of AI-assisted ra-diomics in PCa MRI images.
10.Male reproductive damage caused by phthalate esters:Progress in research
National Journal of Andrology 2024;30(1):66-71
Phthalate esters are plasticizers that people are often exposed to in daily life.They are closely related to our lives and generally exist in the air,soil and water.Studies show that the exposure to phthalates is associated with male reproductive damage.When the concentration of phthalates reaches a certain level in the body,it can reduce the count and motility of sperm,induce abnor-malities in the reproductive system and organs,and affect male fertility.This review summarizes the advances in the studies of the met-abolic pathway of phthalate esters in the human body,the mechanism underlying their damage to the male reproductive system and their antagonistic effect.

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