ABSTRACT
Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.
Subject(s)
Adult , Humans , Male , Asthenozoospermia/genetics , Dyneins/genetics , East Asian People , Kartagener Syndrome/genetics , Mutation , Proteins/genetics , Semen/metabolismABSTRACT
Recent research has highlighted structural and functional abnormalities in the cerebral cortex of patients with premature ejaculation (PE). These anomalies could play a pivotal role in the physiological mechanisms underlying PE. This study leveraged functional magnetic resonance imaging (fMRI), a noninvasive technique, to explore these neural mechanisms. We conducted resting-state fMRI scans on 36 PE patients and 22 healthy controls (HC), and collected data on Premature Ejaculation Diagnostic Tool (PEDT) scores and intravaginal ejaculation latency time (IELT). Employing a surface-based regional homogeneity (ReHo) approach, we analyzed local neural synchronous spontaneous activity, diverging from previous studies that utilized a volume-based ReHo method. Areas with significant ReHo differences between PE and HC groups underwent surface-based functional connectivity (FC) analysis. Significant discrepancies in ReHo and FC across the cortical surface were observed in the PE cohort. Notably, PE patients exhibited decreased ReHo in the left triangular inferior frontal gyrus and enhanced ReHo in the right middle frontal gyrus. The latter showed heightened connectivity with the left lingual gyrus and the right orbital superior frontal gyrus. Furthermore, a correlation between ReHo and FC values with PEDT scores and IELT was found in the PE group. Our findings, derived from surface-based fMRI data, underscore specific brain regions linked to the neurobiological underpinnings of PE.
Subject(s)
Male , Humans , Premature Ejaculation , Brain Mapping/methods , Brain , Cerebral Cortex , Magnetic Resonance Imaging/methodsABSTRACT
BACKGROUND@#The precise pathophysiology of venous erectile dysfunction (VED) was still unclear. Dynamic infusion cavernosometry and cavernosography (DICC) was the gold standard approach for the diagnoses of VED. However, a standard operative procedure of DICC was needed and it was unclear whether DICC could show promise in accurate assessment and treatment of VED. The aim of this study was to establish an optimized operation process of DICC and evaluate the efficacy of DICC in the diagnoses and therapy of VED.@*METHODS@#One hundred and forty-seven VED patients identified by the color doppler duplex ultrasonography (CDDU) were included. Then the method of DICC was adopted to assess the severity of VED and all patients were divided into 4 groups, including (1) non-VED; (2) mild VED; (3) moderate VED and (4) severe VED. All patients received the treatment of psychotherapy. Drug therapy, the intervention embolism of corpus cavernosum and the implantation of penile prosthesis were applied if psychotherapy was ineffective for patients. The international index of erectile function (IIEF-5) scores of patients were collected and compared before and after treatment.@*RESULTS@#IIEF-5 score of non-VED group after psychotherapy (19.35 ± 3.59) and drug therapy (23.31 ± 0.75) was higher than that before psychotherapy (15.30 ± 2.72, t = -4.31, P 0.05). IIEF-5 score of severe VED group was increased under the treatment of implantation of penile prosthesis (23.25 ± 0.71) compared with that before treatment (8.00 ± 0.39, t = -53.25, P < 0.05).@*CONCLUSION@#DICC was a valid diagnostic tool that could identify patients with VED. And DICC had great effect on the diagnosis and individual therapy for patients with VED in varying degrees. Moreover, the manipulation of DICC needed uniform standards.
Subject(s)
Adult , Humans , Male , Middle Aged , Embolization, Therapeutic , Impotence, Vasculogenic , Diagnosis , Therapeutics , Penis , Diagnostic Imaging , Ultrasonography, Doppler, Color , VeinsABSTRACT
Premature ejaculation (PE) is a most common type of ejaculatory dysfunction, which has significant adverse effects on the life quality of the patients and their partners. Medication is currently the first choice for PE and psycho-behavior therapy is sometimes used as an adjuvant means. It is reported in a number of studies that medication alone or combined with psycho-behavior therapy has a great short-term efficacy and a very low risk of side effects. Conservative therapies for PE, however, have some obvious disadvantages such as easy recurrence after drug withdrawal, ineffectiveness in some cases, and so on. Thus, clinicians in China and abroad have developed and tried various surgical methods for the treatment of PE, most of which are reportedly safe and effective. However, International Society for Sexual Medicine guidelines for the diagnosis and treatment of PE recommended against surgical methods because of possible permanent loss of sexual function and insufficient reliable data, though without support from evidence or relevant literature. Although controversial, surgical treatment remains an effective and feasible strategy for refractory PE that does not respond to any conservative therapies. This review summarizes a variety of surgical techniques for PE, along with their basic principles, indications, effects and safety.
Subject(s)
Humans , Male , Behavior Therapy , China , Conservative Treatment , Ejaculation , Premature Ejaculation , Drug Therapy , General Surgery , Quality of Life , Recurrence , Sexual PartnersABSTRACT
Objective@#To investigate the effect of laparoscopic extraperitoneal (LSEP) high ligation of the spermatic vein in the treatment of varicocele.@*METHODS@#We retrospectively analyzed the clinical data about 80 cases of varieocele, 48 treated by LSEP and the other 32 by laparoscopic transabdominal retroperitoneal (LSTR) high ligation of the spermatic vein. We recorded the semen parameters before and at 1, 3 and 6 months after surgery, intraoperative blood loss, operation time, postoperative complications, time of gastrointestinal function recovery and rate of pregnancy, followed by comparison of the data obtained between the two groups of patients.@*RESULTS@#Semen parameters were remarkably improved in both the LSEP and LSTR groups of patients postoperatively as compared with the baseline (P 0.05). The intraoperative blood loss was less in the LSEP than in the LSTR group ([8.3 ± 5.2] vs [9.1 ± 6.1] ml, P >0.05), the operation time was shorter in the former than in the latter ([38.27 ± 9.23] vs [43.46 ± 11.72] min, P >0.05), and so was the time of gastrointestinal function recovery ([1.27 ± 0.26] vs [2.43 ± 0.41] d, P 0.05).@*CONCLUSIONS@#Laparoscopic extraperitoneal high ligation of the spermatic vein is safe and effective and has the advantage of quick recovery in the treatment of varicocele.
Subject(s)
Female , Humans , Male , Pregnancy , Blood Loss, Surgical , Emphysema , Laparoscopy , Ligation , Methods , Operative Time , Postoperative Complications , Recurrence , Retroperitoneal Space , Retrospective Studies , Scrotum , Spermatic Cord , Treatment Outcome , Varicocele , General Surgery , Veins , General SurgeryABSTRACT
Objective@#To investigate the clinical effect of microscopic spermatic vein ligation in the treatment of nutcracker phenomenon (NCP) complicated with left varicocele (VC).@*METHODS@#This retrospective study included 31 cases of NCP complicated with left VC treated in our hospital by subinguinal microscopic ligation of the left spermatic vein (group A, n = 11), open retroperitoneal high ligation of the left spermatic vein (group B, n = 11), or conservative therapy (group C, n = 9). The patients were followed up for 6-24 (15.3 ± 5.4) months. We compared the semen parameters, spermatic vein diameter, left testis volume, and recurrence rate among the three groups of patients before and after treatment.@*RESULTS@#Compared with the baseline, the semen quality parameters were significantly improved in both groups A and B at 6 months after treatment (P0.05), B ([9.77 ± 2.03] vs [9.96 ± 1.72] ml, P>0.05), or C ([9.83 ± 1.59] vs [10.48 ± 2.05] ml, P>0.05), nor in the recurrence rate between groups A and B (P>0.05).@*CONCLUSIONS@#Hematuria, proteinuria and other mild symptoms of nutcracker phenomenon complicated with left VC can be treated palliatively by microscopic ligation of the spermatic vein, which can relieve the clinical symptoms, improve the semen quality, and protect the testicular function of the patient.
Subject(s)
Humans , Male , Follow-Up Studies , Ligation , Methods , Recurrence , Renal Nutcracker Syndrome , General Surgery , Retroperitoneal Space , Retrospective Studies , Semen Analysis , Testis , Time Factors , Varicocele , Veins , General SurgeryABSTRACT
Objective@#To investigate the effect and safety of contrast-enhanced ultrasonography (CEUS) in the diagnosis of venous erectile dysfunction (VED).@*METHODS@#From June 2015 to March 2016, 43 ED patients underwent corpus cavernography, of whom 23 were diagnosed with and the other 20 without corpus cavernosal venous leakage (CCVL). All the patients received intracorporal injection of a vasoactive drug and CEUS.@*RESULTS@#Of the 23 patients with CCVL, 21 were confirmed by CEUS, including 12 cases of double venous leakage, 2 cases of single venous leakage, 5 cases of crural venous leakage, and 2 cases of the mixed type, while the other 2 showed no CCVL on CEUS. Of the 20 patients with CCVL, 2 presented CCVL on CEUS.@*CONCLUSIONS@#CEUS has the advantages of accuracy, safety, and less invasiveness in the diagnosis of VED.
Subject(s)
Humans , Male , Contrast Media , Impotence, Vasculogenic , Diagnostic Imaging , Injections , Penis , Diagnostic Imaging , Ultrasonography , Methods , VeinsABSTRACT
<p><b>Objective</b>To investigate the potential role of the RhoA/Rock signaling pathway in the formation of prostate cancer and the effects of the Rock inhibitor fasudil on the invasion, migration and apoptosis of human prostate cancer cells.</p><p><b>METHODS</b>Human prostate cancer cell lines PC3 and DU145 were treated with fasudil at the concentrations of 5, 10, 20, 40, 80, and 160 μmol/L, respectively, and those as negative controls cultured in the Ham's-F12 medium, all for 24 hours. Then, MTT assay was used to measure the cell inhibition rate and half maximal inhibitory concentration (IC50) value of fasudil, with 1/4 of IC50 as the medication dose for further investigation. The expressions of RhoA, RockⅠ, and RockⅡ proteins in the PC3 and DU145 cells were detected by Western blot and immunohistochemistry, and the invasion, migration and apoptosis of the cells were determined using the Transwell chamber, scratch wound healing assay and flow cytometry.</p><p><b>RESULTS</b>Fasudil inhibited the proliferation of the PC3 cells from (9.29±1.23)% at 5 μmol/L to (81.37±3.97)% at 160 μmol/L and that of DU145 from (7.59±1.54)% to (76.53±2.67)%, both in a dose-dependent manner (P<0.05 ). Significantly fewer PC3 and DU145 cells migrated into the lower compartment in the experimental group (39.2±8.4 and 34.2±6.7) than in the negative control (116.8±9.3 and 112.5±10.8) (P<0.05 ). The wound healing rates of the PC3 and DU145 cells were remarkably lower in the former ([37.26±1.17]% and [32.38±2.73]%) than in the latter ([78.12±4.16]% and [69.47±6.71]%) (P<0.05 ). Annexin V-FITC/PI double staining showed markedly increased apoptosis rates of PC3 and DU145 cells treated with fasudil ([31.88±2.49]% and [28.65±2.99]%) as compared with the negative controls ([7.51±2.28]% and [7.13±1.61]%) (P<0.05 ). The expressions of RockⅠ and RockⅡ were significantly reduced in the fasudil-treated cells in comparison with those of the control group (P<0.05 ) while that of RhoA showed no significant difference between the two groups (P>0.05 ).</p><p><b>CONCLUSIONS</b>The RhoA/Rock signaling pathway may play an important role in the formation of prostate cancer. Fasudil can significantly inhibit the proliferation, migration, and invasion and promote the apoptosis of human prostate cancer PC3 and DU145 cells by reducing RhoA/Rho kinase activity.</p>
Subject(s)
Humans , Male , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine , Pharmacology , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Prostatic Neoplasms , Drug Therapy , Pathology , Signal Transduction , rho-Associated KinasesABSTRACT
<p><b>OBJECTIVE</b>To compare the effects and complications of subinguinal microscopic ligation, laparoscopic transperitoneal varicocelectomy, laparoscopic retroperitoneal varicocelectomy, open retroperitoneal high ligation, and interventional embolotherapy in the treatment of varicocele.</p><p><b>METHODS</b>We conducted a retrospective study that included 632 varicocele patients treated by subinguinal microscopic ligation (group A, n = 79), laparoscopic transperitoneal varicocelectomy (group B, n = 120), laparoscopic retroperitoneal varicocelectomy (group C, n =137), open retroperitoneal high ligation (group D, n = 283), and interventional embolotherapy (group E, n = 13). We compared the baseline and 3-month postoperative semen parameters, postoperative complications, and pregnancy rate among the five groups of patients.</p><p><b>RESULTS</b>The operation time was longer in groups A ([2.02 ± 1.25] h) and E ([2.17 ± 1.02] h) than in the other three groups, while the postoperative hospital stay was the shortest in group E ([1.1 ± 0.1] d). Intestinal injury or incision bleeding occurred intraoperatively in 2 cases in group B and 1 case in group E. Postoperative scrotal edema developed in 3.7, 17, 10, and 19% of the patients in groups A, B, C, and D, respectively, but not in group E. The rate of 1-year recurrence was the lowest in group A (1.6%) and highest in group E (22%). Sperm concentration and the percentages of progressively motile sperm and morphologically normal sperm were improved postoperatively in all the patients (P < 0. 05), but there were no statistically significant differences among the five groups either in the above three parameters or in the postoperative pregnancy rate (P > 0. 05).</p><p><b>CONCLUSION</b>In the surgical treatment of varicocele, laparoscopic retroperitoneal approach involves short operation time and few complications, subinguinal microscopic ligation has the advantages of little injury, rapid recovery, and few complications but requires specialized microsurgical techniques, and interventional embolotherapy leaves no incision scar and needs only local anesthesia and 1-day postoperative hospital stay, which is uitable for those with a contraindication to anesthesia.</p>