Heat Stroke Induces Pyroptosis in Spermatogonia via the cGAS-STING Signaling Pathway.

To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.

The application of the modified Snodgrass technique in hypospadias surgery.

OBJECTIVE: We aimed to explore the effectiveness of the modified tubularized incised plate urethroplasty (Snodgrass Technique) in hypospadias surgery. PATIENTS AND METHODS: A study was conducted on 50 pediatric patients with hypospadias treated in our hospital from May 2020 to May 2023. The patients were divided into two groups based on the condition of their urethral plate; 22 patients were included in the study group and 28 patients were included in the control group. The control group underwent the traditional Snodgrass technique, while the study group received the modified Snodgrass technique. The two groups were compared in terms of treatment efficacy, preoperative and postoperative 6-month Hypospadias Objective Scoring Evaluation (HOSE) scores, surgical data, and postoperative complications. RESULTS: The operation time for the study group was longer than that of the control group, and the intraoperative blood loss was less, but the differences were not statistically significant (p > 0.05). The success rate of surgery in the study group was 95.45% (21/22), compared to 71.43% (20/28) in the control group, showing a statistically significant difference (p < 0.05). The maximum urinary flow rate at 3 and 6 months postoperatively was significantly higher in the study group than in the control group (p < 0.05). The time to maximum flow (TQmax) and post-void residual (PVR) at 3 and 6 months postoperatively were significantly lower in the study group (p < 0.05). A total of 3 patients in the cohort developed urethral fistulas, all between 0.10 cm x 0.10 cm and 0.15 cm x 0.15 cm in size. By instructing the patients to apply pressure to the fistula during urination, all fistulas closed between 3 and 6 months postoperatively. The incidence of postoperative complications was 4.55% in the study group and 28.57% in the control group, a difference that was statistically significant (p < 0.05). CONCLUSIONS: The modified Snodgrass technique shows significant therapeutic effectiveness in hypospadias surgery, substantially increasing the success rate and reducing postoperative complications in pediatric patients, making it suitable for widespread application.

Unintended placement of a double-J stent in the contralateral renal pelvis during laparoscopic pyeloplasty for pediatric hydronephrosis: a case report.

BACKGROUND: The double-J stent (DJS) is a commonly used ureteral stent in urological surgeries, which provides support and drainage. However, the DJS may result in various complications such as infection, hematuria, stone formation, stent occlusion, and migration. Normally, one end of the DJS is located in the renal pelvis, and the other end in the bladder. In this case report, we describe the rare occurrence of a misplaced DJS during laparoscopic pyeloplasty, which was unintentionally placed in the contralateral renal pelvis. CASE REPORT: A 4-month-old male infant was diagnosed with left hydronephrosis. After confirmation of the diagnosis, laparoscopic left pyeloplasty was performed with the placement of a DJS. The patient did not experience any discomfort, such as nausea, vomiting, refusal to feed, crying and restlessness, or fever, after the operation, and was discharged on postoperative day 4. The patient returned to the hospital for DJS removal 6 weeks after the operation. However, the kidneys, ureters, and bladder (KUB) X-ray examination showed that the DJS was unintentionally placed in the contralateral ureter and renal pelvis. The stent was confirmed and removed under cystoscopy. Postoperative examination of the DJS showed that there was a hole in the side of the middle of the stent for urine drainage, with no obstruction or contralateral hydronephrosis. CONCLUSIONS: Misplacement of a DJS in the contralateral renal pelvis during laparoscopic pyeloplasty is a rare but potentially serious complication. Surgeons should be cautious when placing the stent and confirm its placement with imaging studies. Patients should be closely monitored for postoperative complications and prompt intervention should be taken if necessary.

Efficacy of the modified Brisson+Devine procedure for the treatment of concealed penis.

OBJECTIVE: This study was performed to evaluate the clinical efficacy of the modified Brisson+Devine procedure in the management of concealed penis. PATIENTS AND METHODS: In this retrospective study, the medical data of 45 children diagnosed with concealed penis who underwent modified Brisson+Devine procedure in the Department of Urology of Anhui Provincial Children's Hospital between January 2019 and December 2021 were analyzed. Follow-up visits were performed at one, three, and six months postoperatively, and outcome measures included postoperative complications and parental satisfaction. RESULTS: All 45 children completed the surgery uneventfully. At 3-4 days after surgery, the penile dressing and the urinary catheter were removed. The patients were discharged 4-5 days postoperatively without ischemic necrosis of metastatic flaps. The follow-up visits spanned from 7 to 33 months, with a mean of 14.6 months. A statistically significant increase in the penile length after surgery was observed (p<0.05). The postoperative penile appearance was good, and the parents of the children had high treatment satisfaction (p<0.05). 38 children developed postoperative transferred flap edema, and the edema disappeared at 3 months postoperatively. CONCLUSIONS: The modified Brisson+ Devine procedure for concealed penis allows maximum use of the foreskin to improve the appearance of the penis and has a high safety profile by reducing postoperative complications, and provides high treatment satisfaction.

MiRNA-20a-5p accelerates the proliferation and invasion of non-small cell lung cancer by targeting and downregulating KLF9.

OBJECTIVE: To uncover the role of microRNA-20a-5p (miRNA-20a-5p) in the progression of Non-small cell lung cancer (NSCLC) and the underlying mechanism. PATIENTS AND METHODS: MiRNA-20a-5p level in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Its level in NSCLC patients with larger or smaller tumor size, and either with lymphatic metastasis or not was examined as well. Regulatory effects of miRNA-20a-5p on viability, cell cycle, and invasiveness of A549 and PC9 cells were assessed. The interaction between miRNA-20a-5p and KLF9 was explored by Dual-Luciferase Reporter Gene Assay and Spearman correlation test. At last, the role of miRNA-20a-5p/KLF9 axis in influencing the progression of NSCLC was determined. RESULTS: MiRNA-20a-5p was upregulated in NSCLC tissues and cell lines. Its level was much pronounced in NSCLC patients with larger tumor size or accompanied with lymphatic metastasis. Overexpression of miRNA-20a-5p in A549 cells enhanced viability, cell ratio in S phase, and invasiveness, while the knockdown of miRNA-20a-5p in PC9 cells achieved the opposite trends. KLF9 was confirmed to be the direct target of miRNA-20a-5p. There was a negative correlation between the expression levels of miRNA-20a-5p and KLF9 in NSCLC tissues. In addition, KLF9 overexpression could reverse the promotive effects of upregulated miRNA-20a-5p on the proliferation and invasiveness of A549 cells. On the contrary, the knockdown of KLF9 reversed the inhibitory effects of downregulated miRNA-20a-5p on cellular behaviors of PC9 cells. CONCLUSIONS: MiRNA-20a-5p stimulates NSCLC to proliferate and invade by targeting KLF9.

[Value of DNA content in comet tail in predicting changes in blood cell counts in workers exposed to benzene].

Objective: To investigate the value of DNA content in comet tail (TailDNA) in predicting the changes in peripheral blood cell counts in workers exposed to benzene. Methods: In 2011, cluster sampling was used to select 150 male workers exposed to benzene in a petrochemical factory. Cubital venous blood and urine samples were collected for routine blood rest, comet assay, and measurement of s-phenylmercapturic acid (SPMA) and urine creatinine. The population was divided into groups according to urinary SPMA or TailDNA, and routine blood test results within 3 years were collected to analyze the changes in blood cell counts. Results: The low-SPMA group had significantly higher white blood cell and neutrophilcounts in all years than the high-SPMA group (P<0.05) . The low-Tail DNA group had a significant increase in platelet count from 2012 to 2014 (P<0.05) , while the high-Tail DNA group had no significant change (P>0.05) . During the 4-year period, the high-TailDNA group had a significantly lower red blood cell count than the low-TailDNA group (P<0.05) . The high-TailDNA group showed a gradual reduction in white blood cell count over time (ß=-0.113, P<0.05) , and the low-TailDNA group showed no trend of the reduction in white blood cell count (P>0.05) . Conclusion: TailDNA can be used to predict the changes in blood cell counts in workers exposed to benzene.

[Association and interaction of heat shock proteins B1 gene and tumor-suppressor protein p53 gene with chromosome damage levels among coke oven workers].

Objective: To investigate the association and interaction of heat shock proteins B1(HSPB1)gene rs2868371 and tumor-suppressor protein p53(TP53)gene rs1042522 polymorphisms with chromosome damage levels among coke oven workers. Methods: We recruited 1 333 male workers from a state-run coke oven plant in Wuhan in September-October 2010. Among them, 949 who had worked in coke oven workplaces, including auxiliary facilities and bottom, side, and top ovens, were nominated as coke oven workers(i.e., exposed), and 384 administrative or medical staff whose workplaces were offices were used as controls. General characteristics and 5 ml of venous blood were collected from each participant. The plasma concentrations of benzo[a]pyrene-diolepoxide(BPDE)-albumin adducts and the lymphocytic micronucleus(MN)frequencies for each individual were detected by ELISA and cytokinesis-block micronucleus assay, respectively. Gene polymorphisms were genotyped using TaqMan assays via quantitative PCR(ABI Prism 7900HT), and the corresponding frequency ratios(FR)with 95% confidence intervals(CI)were computed for all assays. Results: In the exposed group, the MN frequencies were higher in HSPB1 rs2868371 GC, CC, and GC+ CC genotype carriers((3.88 ± 2.88)‰,(4.00 ± 2.66)‰, and(3.91 ± 2.83)‰, respectively)than in rs2868371 GG genotype carriers((3.52±2.67)‰; FR=1.10, 1.13, and 1.11; 95% CI: 1.02-1.19, 1.02-1.25, and 1.03-1.19, respectively), and the HSPB1 rs2868371C allele was associated with increased MN frequency(Ptrend=0.006). Further, in the exposed group, the MN frequencies were lower in TP53 rs1042522 CG and CG+GG genotype carriers((3.63±2.61)‰ and(3.66±2.61)‰, respectively)than in TP53 rs1042522 CC genotype carriers(3.95±3.06)‰(FR=0.87 and 0.90; 95% CI: 0.83-0.96 and 0.84-0.97, respectively). The effect of gene-gene interaction between HSPB1, rs2868371, and TP53 rs1042522 on MN frequency was significant among coke oven workers(P=0.001). Further stratified analyses showed that the effects of the HSPB1 rs2868371C allele in increasing MN frequencies were robust in subjects aged >40 years(FR=1.07, 95% CI: 1.01-1.12), those working >20 years(FR=1.08, 95% CI: 1.02-1.14), those with BMI ≤24 kg/m2(FR=1.07, 95% CI: 1.01-1.13), drinkers(FR=1.09, 95% CI: 1.02-1.16), and workers with higher BPDE-albumin adduct levels(FR=1.07, 95% CI: 1.01-1.13)(Ptrend=0.023, 0.013, 0.029, and 0.020, respectively). The decreasing effect of the TP53 rs1042522 G allele on MN frequencies was robust in subjects aged >40 years(FR=0.94, 95% CI: 0.89-0.99), those with BMI ≤24 kg/m2(FR=0.94, 95% CI: 0.88-0.99), and drinkers(FR=0.94, 95% CI: 0.88-1.00)(Ptrend=0.031, 0.023, and 0.038, respectively). In addition, there were interactions between HSPB1 rs2868371 and age and between HSPB1 rs2868371 and working years in terms of MN frequency(P=0.030 and 0.013, respectively). Conclusion: In coke oven workers, the HSPB1 rs2868371 C and TP53 rs1042522 G alleles were associated with increased and decreased chromosome damage levels, respectively, and their interaction effect on chromosome damage levels was significant.