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Background: CD2-associated protein (CD2AP) is a podocyte-associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC., Methods: Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT-qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan-Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP-related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor-infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells., Results: We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration., Conclusions: Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) is effective in alleviating cognitive deficits in Alzheimer's disease (AD). However, the strategy for target determination and the mechanisms for cognitive improvement remain unclear., Methods: One hundred and thirteen elderly subjects were recruited in this study, including both cross-sectional (n = 79) and longitudinal experiments (the rTMS group: n = 24; the sham group: n = 10). The cross-sectional experiment explored the precise intervention target based on the cortical-hippocampal network. The longitudinal experiment investigated the clinical efficacy of neuro-navigated rTMS treatment over a four-week period and explored its underlying neural mechanism using seed-based and network-based analysis. Finally, we applied connectome-based predictive modeling to predict the rTMS response using these functional features at baseline., Results: RTMS at a targeted site of the left angular gyrus (MNI: -45, -67, 38) significantly induced cognitive improvement in memory and language function (p < 0.001). The improved cognition correlated with the default mode network (DMN) subsystems. Furthermore, the connectivity patterns of DMN subsystems (r = 0.52, p = 0.01) or large-scale networks (r = 0.85, p = 0.001) at baseline significantly predicted the Δ language cognition after the rTMS treatment. The connectivity patterns of DMN subsystems (r = 0.47, p = 0.019) or large-scale networks (r = 0.80, p = 0.001) at baseline could predict the Δ memory cognition after the rTMS treatment., Conclusion: These findings suggest that neuro-navigated rTMS targeting the left angular gyrus could improve cognitive function in AD patients. Importantly, dynamic regulation of the intra- and inter-DMN at baseline may represent a potential predictor for favorable rTMS treatment response in patients with cognitive impairment., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Recently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis., Methods: Based on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters A-C) and characterized the prognosis and immune infiltration of these clusters. IRFscore constructed by principal component analysis was performed to quantify IRF-related subtypes in individual patients., Results: We proved that IRFscore predicted multiple patient characteristics, with high IRFscore group having poorer prognosis, suppressed TME, increased T-cell exhaustion, increased TMB and greater sensitivity to anti- PD-1/CTLA-4 therapies. Furthermore, analysis of metastatic ccRCC (mccRCC) molecular subtypes and drug sensitivity proved that low IRFscore was more sensitive to targeted therapies. Moreover, IRFscore grouping can be well matched to the immunological and molecular typing of ccRCC. qRT-PCR showed differential expression of IRFs in different cell lines., Conclusions: Evaluating IRF-related molecular subtypes in individual ccRCC patients not only facilitates our understanding of tumour immune infiltration, but also provides more effective clinical ideas for personalised treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Chen, Yang, Zhang, Shao and Xu.)

Objective: To evaluate the feasibility of cervical laminoplasty with preservation of the posterior ligament complex for enlarging the spinal canal. Methods: Six up-to-standard human corpse specimens were divided into two groups by simple randomization (start from C4 group, S4; start from C5 group, S5; 3 corpses in each group). Decompression operation of C3-C6 level was performed in a predetermined sequence by using the new procedure with preservation of the posterior ligament complex.The basic depth of spinal canal was measured with a depth gauge at fixed point after the right bone groove of single level was completed.The operation of the contralateral bone groove was continued, and then the spinal canal was measured again when the spinous process was pulled backward by using a tissue forceps until the ligament complex was just tight.Retreat value (RV) of vertebral lamina was obtained by calculating the difference between the two measurements.The earlier measured levels needed to be remeasured when the operation area increased by one level. Two independent sample and one-sample t test were used to analyze the measurement results. Results: RV of vertebral lamina was small after finishing the first level of the decompression operation [S4: (0.87±0.72) mm; S5: (1.83±0.29) mm], and the value reached its maximum after the completion of C3-C6 level.The overall average RVmaxs from C3 to C6 level were (2.37±0.52) mm, (4.27±0.78) mm, (3.73±0.93) mm and (2.16±0.77) mm, respectively.The overall average retreat rates (RR) were 17%±7%, 32%±9%, 29%±10% and 16%±6%, respectively. The overall average RVmax of C4 and C5 level reached or exceeded the decompression threshold value of 4 mm ( t =0.839, -0.703, both P >0.05). The average RVmax of C4/C5 level was similar in the two groups ( t =-1.204, 1.189, both P >0.05); however, the difference of average RVmax between C3 and C6 level was significant ( t =-4.429, 4.196, both P <0.05). Conclusions: Cervical laminoplasty with preservation of the posterior ligament complex can enlarge the sagittal diameter of spinal canal and relieve the compression of spinal cord.In addition, RV of each level increases as the number of the operation level increases, and the ability of vertebral lamina to retreat is quite different from C3 to C6 level.The decompression effect in the middle of the operation area is better than that on the cranial and tail side.

Objective: To investigate the expressions and action mechanisms of nerve growth factor (NGF) receptors TrkA and p75NTR in the oncogenesis and progression of prostate cancer (PCa)., Methods: Using immunohistochemistry, we detected the expressions of TrkA and p75NTR in 62 PCa and 35 benign prostatic hyperplasia (BPH) samples, and conducted statistical analysis on the basis of clinical data., Results: Independent-samples t-test showed that, along with poorer tissue differentiation or higher clinical stage of PCa, the expression of TrkA was significantly up-regulated, that of p75NTR remarkably down-regulated, and the expression ratio of TrkA to p75NTR markedly increased. The TrkA/p75NTR ratio was 0.32 in the BPH, 0.52 in the PCa tissue with Gleason score of 6, 1.65 in the PCa tissue with Gleason score of 7, 5.75 in the PCa tissue with Gleason score ≥ 8, 0.89 in the clinical stage of pT2, 1.5 in pT3 a, 3.75 in pT3b, and 7.00 in pTxN1., Conclusion: The abnormally increased expression ratio of TrkA to p75NTR might be one of the essential features of malignant transformation of prostate cells. A higher TrkA/p75NTR expression ratio may be associated with a lower tissue differentiation, a higher clinical stage or Gleason score, and therefore a poorer prognosis.

Objective: To evaluate the effect of adjuvant hormonal therapy (AHT) immediately after radical surgery for high- risk organ-confined or locally advanced prostate cancer using the PSA-related biochemical relapse rate within 2 years after surgery., Methods: We retrospectively analyzed 62 cases of high-risk organ-confined or locally advanced prostate cancer. The patients were treated by laparoscopic radical prostatectomy or radical retropubic prostatectomy after MRI and ECT systemic bone imaging examination, which revealed no regional lymph node or bone metastasis. Thirty-two of the patients (group A) received AHT orally or subcutaneously from 2 weeks to 1 months after operation, and another 30 (group B) were left untreated. We followed up the patients for 2 years, measuring the serum PSA level every 3 months, performing ECT every 6 months, and recording the adverse reactions, medication dura- tion, and the patients'quality of life., Results: All the operations were successfully accomplished. The rate of 2-year biochemical relapse-free survival was 78.13% (25/32) in group A and 53.33% (16/30) in group B., Conclusion: AHT immediately after radical surgery can improve the rate of biochemical relapse-free survival of the patients with high-risk organ-confined or locally advanced prostate cancer and check the progression and metastasis of the disease.

The purpose of this study was to describe a new simplified technique for facilitating vesicourethral anastomosis in laparoscopic radical prostatectomy. After prostate removal, an approximately 15-cm-long absorbable suture with one three-eighths arc needle is passed from the outside in on the full thickness of the bladder neck at the 9 o'clock position and then from inside out on the full thickness of the urethra at the 9 o'clock position. It is knotted with the suture tail. Subsequently, a continuous suture is completed between the bladder neck and urethra. A 20-French silastic catheter is placed into the bladder before completing the anterior row of sutures. Three hundred twelve consecutive patients with localized prostate cancer who had undergone the new simplified vesicourethral anastomosis were included in this retrospective study. The average time of anastomosis was 10.5 minutes (range, 8-30 minutes), as recorded for an experienced laparoscopic surgeon. The incidence rate was 2.2% for urine leakage and 1.3% for bladder neck stenosis, and the continence rate was 86.9% at 1 month, 93.3% at 3 months, 98.1% at 6 months, and 98.7% at 1 year. We present a new simplified method for vesicourethral anastomosis. The method takes little operating time and is easy for novice laparoscopists to master. Moreover, this technique has low rates of urinary leakage and bladder neck stricture.

This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis (TNM) staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma (RCC) patients. A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled. All of the patients had pathologically confirmed clear cell RCC (ccRCC). All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review, and survival data were collected. Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival (CSS) and progression-free survival (PFS) after surgery. Continuous variables, such as age and tumour diameter, were calculated as mean values and standard deviations (s.d.) or as median values. Survival was calculated by the Kaplan-Meier method, and the log-rank test assessed differences between groups. Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system. Therefore, the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients. However, when using the revised 2010 staging system, we found that more than 92% of patients (288/313) with T3 tumours were staged in the T3a subgroup, and their survival data were not significantly different from those of patients with T2b tumours. In addition, T2 subclassification failed to independently predict survival in RCC patients.

The hypoxia-inducible factor-1α (HIF-1α) plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIF1A (coding HIF-1α) have been shown to influence an individual's susceptibility to many human tumors; however, evidence on associations between HIF1A single-nucleotide polymorphisms (SNPs) and prostate cancer (PCa) risk is conflicting. We genotyped three potentially functional polymorphisms in HIF1A (rs11549465, rs11549467 and rs2057482) using the TaqMan method and assessed their associations with PCa risk in a case-control study of 662 PCa patients and 716 controls in a Chinese Han population. Compared with rs11549467 GG genotype, the variant genotypes GA+AA had a significantly increased PCa risk (adjusted odds ratio (OR)=1.70; 95% confidence interval (CI)=1.06-2.72), particularly among older patients (OR=2.01; 95%CI=1.05-3.86), smokers (OR=2.06; 95%CI=1.07-3.99), never drinkers (OR=2.16; 95%CI=1.20-3.86) and patients without a family history of cancer (OR=1.71; 95%CI=1.02-2.89). Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score (OR=2.14; 95%CI=1.22-3.75). No altered PCa risk was associated with the rs11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs11549467 were associated with increased PCa risk (OR=2.10; 95%CI=1.23-3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.

Objective: To investigate the safety and feasibility of glans-preserving surgery in the treatment of superficial penile cancer (SPCa)., Methods: We retrospectively analyzed the clinical data of 21 cases of SPCa treated by glans-preserving surgery in our hospital from January of 2003 to March of 2010., Results: The study included 21 SPCa patients aged 36 to 57 (mean 46) years, with superficial lesions involving the glans penis, coronary sulcus or shaft skin. The tumors were staged and graded TaG1 in 6 cases, TaG2 in 5, TisG1 in 2, TisG2 in 4, T1G1 in 3, and T1G2 in 1. All the patients underwent glans-preserving surgery to preserve the normal appearance and functional integrity of the glans penis, and all returned to normal sexual activity 1 month after operation, with good sexual function and sexual satisfaction. Postoperative follow-up lasted 2 to 7 (mean 5) years, and 2 cases of recurrence in situ found at 6 and 9 months, respectively, which were successfully managed by a second glans-preserving surgery., Conclusion: Glans-preserving surgery is an effective method for superficial penile cancer. With proper selection of the patients, this procedure is technically safe, maximally preserves the penile appearance, and least affects the patients' sexual satisfaction.

Objective: To evaluate the technique and clinical outcomes of modified transperitoneal laparoscopic radical prostatectomy., Methods: A total of 105 patients received the operation with age ranging from 51 to 73 years from January 2008 to June 2010. Mean level of serum prostate specific antigen was 13.6 µg/L and mean prostatic volume was 45 ml. Pathological studies of biopsy confirmed the prostate carcinoma with Gleason score 6-8. Radionuclide bone scan revealed no metastasis. Based on previously retroperitoneal radical prostatectomy, modified technique was applied involving surgical approach, bladder neck dissection and vesicourethral anastomosis., Results: Mean operative time was 93 min (65 - 150 min). Intraoperative blood loss was 115 ml (50 - 400 ml). No complication of bowl injury occurred. Positive surgical margin was present in 24 patients. Normal continence were seen in 64 patients after catheter removed. Recovery of incontinence within 3 months was seen in 33 patients and 3 to 12 months in 5 patients respectively. Three patients with incontinence were still in the follow-up., Conclusions: Transperitoneal laparoscopic radical prostatectomy provides large working space and clear anatomic exposure. Higher efficiency and lower complication rate are obtained through modified laparoscopic technique involving seminal vesicle isolation, bladder neck dissection and vesicourethral anastomosis.

Objective: To investigate the impact of congenital cytomegalovirus infection on the hearing ability in infants., Methods: By using the tools of distortion product otoacoustic emission (DPOAE) and auditory brain-stem response (ABR), the hearing ability of 38 infants with congenital cytomegalovirus infection and 16 cases of normal controls during neonatal periods was screened with a follow-up study at 6 and 24 months., Result: In infants with congenital cytomegalovirus infection, 86.8% (66/76) ears at neonatal stage and 76.3% (58/76) ears at 6 months passed the tests; while in normal controls, 96.9% (31/32) ears passed the tests. The reaction threshold of ABR V in infants with congenital cytomegalovirus infection was higher than that in normal controls (P<0.005). Furthermore,in infants with congenital cytomegalovirus infection, 13 ears (17.1%) were extreme hearing loss, 5 ears (6.6%) were severe hearing loss, and 6 ears (7.9%) were moderately severe hearing loss. The incidence of hearing loss during the follow-up was 7.9% (3/38) at neonatal stage, 23.7% (9/38) at 3-4 months, and 7.9% (3/38) after 6 months., Conclusion: The congenital cytomegalovirus infection could cause the prompt and late-onset hearing loss. The combination of the laboratory evidence with the dynamic hearing screening may contribute to the early detection of hearing loss in infants with congenital cytomegalovirus infection.