CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

[Advantage analysis of modified day surgery procedure for concealed penis].

OBJECTIVE: The modified day surgery procedure was compared with traditional inpatient procedure and standard day surgery procedure of concealed penile surgery to investigate its advantages, as well as the feasibility of promoting it in our country. METHODS: Retrospective analyzing the clinical data between 135 cases of the concealed penis in children who underwent modified day surgery (day group) and 101 cases who underwent hospitalization surgery (hospitalization group) at the Second Hospital of Hebei Medical University and the results of follow-up.The modified day surgery procedure involves the establishment of dedicated day wards in each surgical department, where the patient's condition is monitored until 8 o'clock the following morning to assess their discharge eligibility.The children's clinical data was divided into two groups to compare clinical parameters, including age at surgery, bleeding volume, operation time, hospitalization expenses, day of hospitalization, and the occurrence of short-term complications before the initial dressing change after surgery.The satisfaction survey of the children was conducted among three distinct groups: the modified day group, the standard day group, and the hospitalization group enabling a comparison of satisfaction levels among these groups. RESULTS: The mean ages of the inpatient and day surgery groups were 8.92±4.42 years old and 11.85±4.43 years old, respectively. No significant differences were observed between these two groups regarding operation time, bleeding volume, and postoperative complications (P>0.05). Compared to the inpatient group, the mean inpatient time and the hospitalization cost of the day group decreased by 69% and 27%, respectively (P<0.05). The patients in the modified procedure group reported the highest satisfaction among the three groups. CONCLUSION: Modified day surgery procedure offers advantages over the standard day surgery procedure and traditional inpatient surgical procedures for the operative treatment of the concealed penis, which makes it suitable for large-scale popularization in China.

[A comparative study of transcolonic and paracolic laparoscopic pyeloplasty in children with UPJO].

OBJECTIVE: Comparing the laparoscopic pyeloplasty via the mesocolon and para-colonic gutter approach for the treatment of pediatric pelvi-ureteric junction obstruction (UPJO) induced simple hydronephrosis, and analyzing the potential factors influencing surgical outcomes. METHODS: Clinical data of 71 children with UPJO who underwent laparoscopic pyeloplasty at the Department of Urology of the Second Hospital of Hebei Medical University from January 2020 to January 2023 were analyzed. The patients, aged 0.25 to 18 years, were divided into two groups: 30 cases underwent the transcolonic route (mesangial group) and 41 cases underwent the transcolonic paragutter route (paragrow group). RESULTS: showed that both surgical approaches had similar outcomes in terms of operation completion, smooth process, absence of laparotomy, operation time, intraoperative blood loss, postoperative feeding time, and postoperative drainage tube indwelling time, total hospitalization cost, surgical effect, and satisfaction. Common complications such as postoperative fever and abdominal pain were managed with drug treatment or observation, with no need for secondary surgery or fatal complications. Factors such as age, body mass index, preoperative symptoms, severity of hydronephrosis, and ABO blood group classification did not impact the surgical outcome. CONCLUSIONS: There was no statistically significant difference between laparoscopic pyeloplasty and another surgical method in terms of various surgical outcomes for children with ureteropelvic junction obstruction. Factors such as age, body mass index, preoperative symptoms, severity of hydronephrosis, and ABO blood group classification did not have a significant impact on the surgical outcome.

[Feasibility low cryptorchidism surgery following modified day surgical procedures].

OBJECTIVE: To explore the feasibility and safety of cryptorchidism surgery in the day surgery center. METHODS: This retrospective study included 122 cases of unilateral low cryptorchidism (ULC) and 27 cases of bilateral low cryptorchidism (BLC) treated by orchidopexy from July 2018 to July 2022 in the Second Hospital of Hebei Medical University. We divided the patients with ULC into an Ad (day surgery following modified day surgical procedures) and an Ac (conventional surgery) group, and those with BLC into a Bd and a Bc group. We analyzed the clinical data and compared the surgical parameters and patients' satisfaction between different groups. RESULTS: There were no statistically significant differences in the operation age, operation time, intraoperative blood loss, or postoperative complications between the Ad and Ac groups (P > 0.05), but the hospital stay and total cost were markedly reduced in the Ad group by 69% and 10%, respectively, compared with those in the Ac group (P < 0.05). No statistically significant differences were observed between the Bd and Bc groups in the operation age or intraoperative blood loss (P > 0.05), but the Bd group showed significant decreases in the operation time, hospital stay (62%) and total cost (14%) in comparison with the Bc group (P < 0.05). The satisfaction of the patients was remarkably higher in the former than in the latter group. CONCLUSION: Low cryptorchidism surgery following the modified day surgical procedures in the day surgery center is safe and feasible, with the advantages of lower cost and shorter hospital stay.

Effect of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with erectile dysfunction.

OBJECTIVE: To evaluate the effect and clinical significance of tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with Erectile dysfunction (ED). METHODS: Eighty patients with hyperlipidemia complicated with ED who were treated at The Second Hospital of Hebei Medical University from January 2019 to June 2020 were selected. Using a completely randomized design experimental method, these 80 patients were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. The control group was treated with a single drug, atorvastatin calcium, while the experimental group was given tadalafil orally on the basis of the control group for 3 months. Changes in the levels of inflammatory factors such as IL-6, TNF and CRP, adverse drug reactions, changes in hemodynamic indicators such as HSV, LSV, PSV, HCT and ESR before and after treatment, as well as changes in sexual function after treatment were compared and analyzed between the two groups. RESULTS: TNF-a, CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with statistically significant differences (p<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (p=0.18). After treatment, hemodynamic indexes and sexual function indexes of the experimental group were significantly improved compared with those in the control group, with statistically significant differences (p<0.05). CONCLUSION: A significant improvement effect can be achieved by tadalafil combined with atorvastatin on hemodynamics and sexual function in middle-aged and elderly patients with hyperlipidemia complicated with ED. At the same time, the combination of the two has synergism on inflammatory factors and blood rheology, and the incidence of adverse reactions is not significantly increased.

Cholinergic α5 nicotinic receptor is involved in the proliferation and invasion of human prostate cancer cells.

Nicotinic acetylcholine receptor (nAChR) subunit α5 (α5­nAChR) is involved in tumor cell proliferation, inhibition of apoptosis, progression of metastasis, and induction of angiogenesis in certain solid tumors. However, the role of α5­nAChR in prostate cancer cell growth and metastasis is unclear. In the present study, the role of α5­nAChR in cell proliferation, migration, invasion and apoptosis was investigated by silencing the expression levels of α5­nAChR in the prostate cancer cell lines DU145 and PC3. A siRNA oligonucleotide targeting α5­nAChR was designed. The cell proliferation of DU145 and PC3 cell lines was analyzed by the Cell Counting Kit­8 (CCK­8) assay. Cell migratory and invasive activities were determined using wound healing and Transwell assays, respectively. Western blot analysis was used to quantify α5­nAChR, p­AKT and p­ERK1/2 levels in DU145 and PC3 cells. Knockdown of α5­nAChR was associated with decreased cell proliferation, migration, invasion and increased apoptosis. In addition, decreased phosphorylation levels of AKT and ERK1/2 were revealed following α5­nAChR knockdown in DU145 and PC3 cells compared with those observed in the scramble control samples. The expression levels of the apoptosis­related proteins were altered following silencing of α5­nAChR. In summary, the data indicated that α5­nAChR was involved in the proliferation and invasion of human prostate cancer cells.

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer.

The transcription factor E2F1 regulates the expression of the miR-20b-5p precursor and is involved in epithelial-to-mesenchymal transition (EMT). Transforming growth factor-ß1 (TGF-ß1) induces EMT in prostate cancer (PCa) by binding to TGF-beta receptor 2 (TGFBR2) to activate TGF-ß signaling. However, the relationship between TGFBR2, E2F1, and miR-20b-5p in the modulation of EMT in PCa cells remains unknown. In this study, we found that the level of miR-20b-5p expression was significantly lower in PC3 and DU145 cells than that in prostate epithelial (RWPE-1) cells, and TGF-ß1 treatment further down-regulated miR-20b-5p expression in these two cell lines. Functional studies showed that miR-20b-5p suppressed TGF-ß1-induced migration and invasion of PC3 and DU145 cells by up-regulating E-cadherin and down-regulating vimentin, leading to TGF-ß1-induced inhibition of EMT. Using gain and loss of function experiments, it was shown that E2F1 mediated TGF-ß1 regulation of miR-20b-5p expression. Further, a luciferase activity assay showed that TGFBR2 was a direct target of miR-20b-5p in PCa cells. These results suggest that miR-20b-5p, TGFBR2, and E2F1 form a regulatory loop to modulate EMT induced by TGF-ß1. A novel regulatory mechanism underlying the miR-20b-5p/TGFBR2/E2F1 axis is involved in TGF-ß1-induced EMT of PCa cells, and miR-20b-5p may be a potential therapeutic target for PCa.

Intervention effect and mechanism of curcumin in chronic urinary tract infection in rats.

OBJECTIVE: To analyze the invention effect of curcumin on chronic urinary tract infection in rats and explore its possible mechanism of action. METHODS: The experimental animals were randomly divided into three groups, normal, model and curcumin group. Chronic urinary tract infection models were built for model group and curcumin group by injecting coliform fluid into the cavity of bladder. From the first day of modeling, rats in the curcumin group were injected with 150 mg/kg curcumin, while rats in normal group and model group were given no other treatment. The treatment lasted for 14 d. The white blood cell counts in blood and urine, bacterial colony count in urine and renal tubular functional indexes of rats in all groups at day 1, 7, and 14 after treatment were detected. Urine ß2-microglobulin (ß2-MG), urinary N-acetyl-ß-D glucosaminidase (NAG) levels were used to detected the inflammatory cytokines in serum after treatment including the contents of IL-6, IL-8, IL-10 and monocyte chemoattractant protein-1 (MCP-1), and real-time PCR was employed to determine the expression of mRNA of toll-like receptor 2 (TLR-2) and TLR-4 in renal tissues and bladder tissues of all groups after treatment. RESULTS: The white blood cell counts at day 1 and 7 after treatment in rats of model group and curcumin group were significantly higher than those of normal group at the same time points, while the white blood cell counts of the curcumin group were significantly lower than those of model group (P < 0.05). The urine white blood cell counts in rats of model group at day 1, 7 and 14 were all significantly higher than those of normal group at the same time points; those in the curcumin group were significantly lower than those of the model group at day 1, 7 and 14 at the same time points (P < 0.05). The bacterial colony counts of urine in rats of model group and curcumin group at day 1, 7 and 14 were all significantly higher than those of normal group at the same time points, while the counts of curcumin group were significantly lower than those of model group at the same time points (P < 0.05). Levels of urine ß2-MG, NAG, IL-6, IL-8, IL-10, MCP-1 and expression of TLR2 mRNA and TLR4 mRNA in renal and bladder tissues in rats of model group were significantly higher than those of the normal group, while these variables of the curcumin group were significantly higher than those of the normal group but lower than those of model group (P < 0.05). CONCLUSIONS: Curcumin can significantly improve the symptoms of chronic urinary tract infections, protect renal tubular function, and also decline inflammatory responses by influencing the expressions of TLR2 mRNA and TLR4 mRNA so as to exert its curative effect on chronic urinary tract infections.

[Transumbilical single-port laparoscopy combined with improved double hernia needles for pediatric hydrocele].

OBJECTIVE: To compare the clinical effect of transumbilical single-port laparoscopy combined with improved double hernia needles with that of traditional open surgery in the treatment of hydrocele in children. METHODS: We retrospectively analyzed 35 cases (54 sides) of pediatric hydrocele treated by transumbilical single-port laparoscopy combined with improved double hernia needles (laparoscopy group). We recorded the operation time, intraoperative blood loss, hospital stay, scrotal edema, and postoperative complications and compared them with those of another 46 cases (58 sides) treated by traditional open surgery (open surgery group) during the same period. RESULTS: The laparoscopy group showed a significantly shorter operation time, less intraoperative blood loss, milder scrotal edema, and fewer hospital days than the open surgery group (all P<0.05). However, no statistically significant difference was found in the incidence of postoperative complications between the two groups (P>0.05). Subcutaneous emphysema developed in 2 patients in the laparoscopy group, which disappeared after 1－3 days of oxygen inhalation and other symptomatic treatment, while scrotal hematoma occurred in 1 and incision fat liquefaction in 2 patients in the open surgery group 3 days postoperatively, which healed after debridement suture and daily dressing, respectively. The patients were followed up for 3－6 months, which revealed no late complications in the laparoscopy group but 1 case of unilateral recurrence and 2 cases of offside recurrence in the open surgery group, all cured by laparoscopic internal ring ligation. CONCLUSIONS: Transumbilical single-port laparoscopy combined with improved double hernia needles is superior to traditional open surgery for the treatment of pediatric hydrocele and therefore deserves clinical generalization.

[The application of tunica vaginalis flap in urethral repair].

OBJECTIVE: To investigate the application of tunica vaginalis flap in repairing the deformity of urethra and urethral fistulas. METHODS: Tunica vaginalis flap from the scrotum were used to wrap the reconstructed urethra in the 38 cases of hypospadias urethroplasty and urethral fistulas repair from 2002. RESULTS: All of cases were followed up for six months to one year. There was a fistula reoccurred after epispadias fistula repair, the repair was successful in other patients. There was no recurrent fistulas or urethral strictures. Penile cosmesis was excellent and erected well. CONCLUSIONS: The application of tunica vaginalis flap in urethral repair can raise achievement ratio and reduce the incidence of urethral fistulas. The flap is ease to mobilize with no harmful effects on the testicles.

[Correction of pediatric concealed penis by using a modified Devine' s technique].

OBJECTIVE: To discuss the diagnosis of pediatric concealed penis and evaluate the results after the correction of the pediatric concealed penis. METHODS: Twenty patients with pediatric concealed penis were treated by using a modified Devine's technique. RESULTS: The appearance with a straightening penile was achieved in all of the patients. All of the patients recovered well after the operation without any complications. CONCLUSIONS: The modified Devine' s technique could be a safe and effective method for the correction of the pediatric concealed penis with satisfactory outcome.