Deep learning models for rapid discrimination of high-grade gliomas from solitary brain metastases using multi-plane T1-weighted contrast-enhanced (T1CE) images.

Background: High-grade gliomas (HGG) and solitary brain metastases (SBM) are two common types of brain tumors in middle-aged and elderly patients. HGG and SBM display a high degree of similarity on magnetic resonance imaging (MRI) images. Consequently, differential diagnosis using preoperative MRI remains challenging. This study developed deep learning models that used pre-operative T1-weighted contrast-enhanced (T1CE) MRI images to differentiate between HGG and SBM before surgery. Methods: By comparing various convolutional neural network models using T1CE image data from The First Medical Center of the Chinese PLA General Hospital and The Second People's Hospital of Yibin (Data collection for this study spanned from January 2016 to December 2023), it was confirmed that the GoogLeNet model exhibited the highest discriminative performance. Additionally, we evaluated the individual impact of the tumoral core and peritumoral edema regions on the network's predictive performance. Finally, we adopted a slice-based voting method to assess the accuracy of the validation dataset and evaluated patient prediction performance on an additional test dataset. Results: The GoogLeNet model, in a five-fold cross-validation using multi-plane T1CE slices (axial, coronal, and sagittal) from 180 patients, achieved an average patient accuracy of 92.78%, a sensitivity of 95.56%, and a specificity of 90.00%. Moreover, on an external test set of 29 patients, the model achieved an accuracy of 89.66%, a sensitivity of 90.91%, and a specificity of 83.33%, with an area under the curve of 0.939 [95% confidence interval (CI): 0.842-1.000]. Conclusions: GoogLeNet performed better than previous methods at differentiating HGG from SBM, even for core and peritumoral edema in both. HGG and SBM could be fast screened using this end-to-end approach, improving workflow for both tumor treatments.

Enhancing generalizability and performance in drug-target interaction identification by integrating pharmacophore and pre-trained models.

MOTIVATION: In drug discovery, it is crucial to assess the drug-target binding affinity (DTA). Although molecular docking is widely used, computational efficiency limits its application in large-scale virtual screening. Deep learning-based methods learn virtual scoring functions from labeled datasets and can quickly predict affinity. However, there are three limitations. First, existing methods only consider the atom-bond graph or one-dimensional sequence representations of compounds, ignoring the information about functional groups (pharmacophores) with specific biological activities. Second, relying on limited labeled datasets fails to learn comprehensive embedding representations of compounds and proteins, resulting in poor generalization performance in complex scenarios. Third, existing feature fusion methods cannot adequately capture contextual interaction information. RESULTS: Therefore, we propose a novel DTA prediction method named HeteroDTA. Specifically, a multi-view compound feature extraction module is constructed to model the atom-bond graph and pharmacophore graph. The residue concat graph and protein sequence are also utilized to model protein structure and function. Moreover, to enhance the generalization capability and reduce the dependence on task-specific labeled data, pre-trained models are utilized to initialize the atomic features of the compounds and the embedding representations of the protein sequence. A context-aware nonlinear feature fusion method is also proposed to learn interaction patterns between compounds and proteins. Experimental results on public benchmark datasets show that HeteroDTA significantly outperforms existing methods. In addition, HeteroDTA shows excellent generalization performance in cold-start experiments and superiority in the representation learning ability of drug-target pairs. Finally, the effectiveness of HeteroDTA is demonstrated in a real-world drug discovery study. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/daydayupzzl/HeteroDTA.

ROCK2 disturbs MKP1 expression to promote invasion and metastasis in hepatocellular carcinoma.

Dual-specificity phosphatase-1 (DUSP1/MKP1) plays a key role in controlling various physiological and pathological phenomena, including tumor metastasis and invasion. However, the role of MKP1 in tumorigenesis is controversial. We showed that the expression of MKP1 in hepatocellular carcinoma (HCC) is significantly downregulated, and MKP1 is an independent predictor of poor prognosis. In in vitro and in vivo studies, we showed that MKP1 significantly inhibits the invasion and metastasis of HCC cells. Additionally, we found that low MKP1 expression is associated with the expression of ROCK2, which plays an important role in HCC. Our data suggest that MKP1 is crucial for ROCK2-mediated metastasis and invasion. Interestingly, we demonstrated that ROCK2 has opposite effects on protein and mRNA levels of MKP1, as it decreases the expression at the protein level and increases the expression at the mRNA level. We also identified the mechanism responsible for this incongruency; ROCK2 activates ERK1/2-ATF2 signaling, which leads to the increased mRNA expression of MKP1. At the same time, ROCK2 promotes the ubiquitin-mediated degradation of MKP1 by activating ERK1/2, therefore promoting the metastasis of HCC. In conclusion, our data provide new evidence for the biological and clinical significance of MKP1 as a potential biomarker. We demonstrate that ROCK2 disturbs the protein and mRNA expression of MKP1 in human HCC progression.

Prospective randomized comparison of transumbilical two-port laparoscopic and conventional laparoscopic varicocele ligation.

We have established a novel method named transumbilical two-port laparoscopic varicocele ligation (TTLVL) for varicocele, which is still needed to evaluate. In this study, 90 patients with left idiopathic symptomatic varicoceles of grades II-III according to the Dubin grading system were randomly assigned to TTLVL (n = 45) and conventional laparoscopic varicocele ligation (CLVL) (n = 45). The demographic, intraoperative, postoperative, and follow-up data were recorded and compared between the two groups. All the procedures in the two groups were completed successfully with no intraoperative complications and no conversions to open surgery. No significant difference was found in the operative time, resuming ambulation, bowel recovery, postoperative hospital stay, and postoperative resolution of scrotal pain between the two groups (P > 0.05). However, the postoperative mean visual analog pain scale scores for TTLVL group were all less at 24 h, 48 h, 72 h, and 7 days postoperatively compared to CLVL (P = 0.001, 0.010, 0.006, and 0.027, respectively). The mean patient scar assessment questionnaire score in postoperative month 3 was 29.7 for TTLVL group compared with 32.1 for CLVL group (P < 0.001). There was no testicular atrophy observed in both groups during the follow-up period. The study shows that TTLVL is a safe, feasible, and effective minimally invasive surgical alternative to CLVL for the treatment of varicocele. Compared with CLVL, TTLVL may decrease postoperative pain and improve the cosmetic outcomes.

Transumbilical multiport laparoscopic nephrectomy with specimen extraction through the vagina.

OBJECTIVES: To report our initial experience with transumbilical multiport laparoscopic nephrectomy (TMLN) with transvaginal specimen extraction. PATIENTS AND METHODS: Between January and July 2010, 5 married and parous female patients were submitted to TMLN with transvaginal specimen extraction in our center. All data referring to patient demographics, surgery, pathology and perioperative outcomes were recorded. Sexual function was assessed with the Female Sexual Function Index questionnaire before and after surgery. The cosmetic result was investigated by administering the Patient Scar Assessment Questionnaire and Scoring System (PSAQ). RESULTS: All procedures were completed successfully. The mean operative time was 136 min (range 110-160 min, standard deviation [SD] 20.7). The mean estimated blood loss was 66 ml (range 40-100 ml, SD 24.1). The mean postoperative hospitalization stay was 4.8 days (range 4-6 days, SD 0.8). All patients reported unaltered sexual function after surgery. The better cosmetic results were confirmed by the PSAQ score. CONCLUSIONS: TMLN with transvaginal specimen extraction is feasible and safe for married and parous female patients. This technique is a natural evolution towards natural orifice transluminal endoscopic surgery (NOTES). By acting as an intermediate-type procedure, it provides a bridge through which NOTES may ultimately gain clinical acceptance.

Pure transvaginal natural orifice translumenal endoscopic surgery for renal cyst decortication: report of initial five cases.

OBJECTIVE: To present our initial experience with pure transvaginal natural orifice translumenal endoscopic surgery renal cyst decortication. METHODS: From December 2010 to July 2011, five female patients with symptomatic renal cyst in the anterior portion and lower pole of the kidney were submitted to pure transvaginal natural orifice translumenal endoscopic surgery renal cyst decortication in our center. Under general anesthesia, the patients were placed in the lithotomy position with the affected side elevated by 60°. A 3-cm incision was made at the posterior vaginal fornix and a modified three-channel port was deployed across the vaginal incision. The cyst was dissected and the cyst fluid was aspirated using a suction device. The cyst wall was circumferentially excised. RESULTS: All five procedures were successfully carried out without additional transabdominal trocars. The median operative time was 80 min (range 60-90 min). The median estimated blood loss was 25 mL (range 25-50 mL). The median visual analog scale score was 1 on postoperative day 1. None of the patients required narcotic pain medications beyond postoperative day 2. Intestinal function recovered on postoperative day 1-3. There was no intraoperative or postoperative complication in any of the patients. During the follow-up visits, all the patients were in good condition. All the patients reported unaltered sexual function after surgery by the Female Sexual Function Index questionnaire. CONCLUSION: Our initial experience suggests that pure transvaginal natural orifice translumenal endoscopic surgery renal cyst decortication is feasible and safe in selected patients.

Suprapubic-assisted laparoendoscopic single-site surgery (LESS) in urology: our experience.

OBJECTIVE: To report our experience with suprapubic-assisted laparoendoscopic single-site surgery (SA-LESS) in urology. PATIENTS AND METHODS: In all, 236 patients underwent SA-LESS A 5- and 10-mm (or two 5-mm) trocars were inserted at the medial margin of the umbilicus. A 10- or 5-mm trocar was inserted into the abdominal cavity below the ipsilateral pubic hairline. The technique for the SA-LESS is similar to that of the standard laparoscopy, with conventional instruments placed in the abdominal trocars, under direct vision achieved by a 10-mm conventional 30 ° or 5-mm flexible-tip 0 ° laparoscope placed through the trocar below the pubic hairline. RESULTS: SA-LESS was successfully completed in 229 patients, without the need for ancillary trocars or additional instruments. Six patients required conversion to standard laparoscopy because of intraoperative bleeding (five) and failure to progress (one). One patient underwent open conversion because of gradual bleeding during the dissection of a dense adhesive renal pedicle due to infection and fibrosis The various SA-LESS procedures performed included adrenalectomy (15), renal cyst excision (19), nephrectomy (78; simple 63, radical 15), nephroureterectomy (three), nephron-sparing surgery (three), heminephroureterectomy (five), pyeloplasty (nine), pyelolithotomy (six), and ureterolithotomy (98). The median operative time was 81, 106, 92, 140, and 85 min, and the estimated blood loss was 60, 205, 115, 75, and 55 mL for adrenalectomy, simple nephrectomy, radical nephrectomy, pyeloplasty, and ureterolithotomy, respectively. At a mean (range) follow-up of 14.8 (2-27) months there was a hidden umbilicus scar. The scar below the pubic hairline was not detectable because of pubic hair covering. CONCLUSIONS: SA-LESS appears to be feasible, safe and effective. Compared with umbilical LESS, the placement of a trocar at the umbilicus and below the pubic hairline not only decreases the difficulty of surgery but also leads to little postoperative pain and good cosmetic results.

CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-MYC protein. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in urothelial cell carcinoma (UCC) of the bladder. CIP2A expression was examined in 20 fresh bladder UCC tissues and paired adjacent normal bladder tissues by RT-PCR and Western blot. Immunohistochemistry for CIP2A was performed on additional 117 bladder UCC tissues. The clinical significance of CIP2A expression was analyzed. CIP2A downregulation was performed in bladder UCC cell line T24 with high abundance of CIP2A, and the effects of CIP2A silencing on cell proliferation, migration, invasion in vitro, and tumor growth in vivo were evaluated. We found that CIP2A expression was upregulated in bladder UCC tissues relative to adjacent normal bladder tissues. Clinicopathological analysis showed that CIP2A expression was significantly associated with tumor stage (P = 0.004), histological grade (P = 0.007), and lymph node status (P = 0.001). The Kaplan-Meier survival curves revealed that CIP2A expression was associated with poor prognosis in bladder UCC patients (log-rank value = 14.704, P < 0.001). CIP2A expression was an independent prognostic marker of overall patient survival in a multivariate analysis (P = 0.015). Knockdown of the CIP2A expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumor growth in xenograft model mice. Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder UCC patients, and inhibition of its expression might be of therapeutic significance.

Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma.

BACKGROUND: Fork head box M1 (FoxM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models. METHODS: Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA) in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed. RESULTS: FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P <0.001), lymph node metastasis (P = 0.01), distant metastasis (P = 0.01), TNM stage (P < 0.001) and histological grade (P = 0.003). The Kaplan-Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P < 0.001). FoxM1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P = 0.008). Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), resulting in the inhibition of migration, invasion, and angiogenesis. CONCLUSIONS: These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a promising therapeutic target for ccRCC.

Transvaginal natural orifice transluminal endoscopic surgery (NOTES)-assisted laparoscopic adrenalectomy: first clinical experience.

BACKGROUND: This study aimed to describe the initial clinical experience of transvaginal natural orifice transluminal endoscopic surgery (NOTES)-assisted laparoscopic adrenalectomy (TNLA) and to evaluate its feasibility and efficacy. METHODS: Between May and December 2010, 11 consecutive women were subjected to TNLA for adrenal tumors at the authors' center. With the patient under general anesthesia, a 5-mm trocar and a 10-mm trocar were inserted in the umbilical edge for conventional operating apparatus, and a 10-mm trocar was inserted in the posterior vaginal fornix for a conventional 30º laparoscope. Dissection was performed according to the method of a standard laparoscopic adrenalectomy. The adrenal gland, its tumor, or both were put into a homemade bag and then removed via the incision of the posterior vaginal fornix after complete resection. RESULTS: A total of 11 TNLAs were performed in this series. Only one conversion to open surgery was performed for one patient with Cushing disease, who was subjected to a splenectomy synchronously for an injury of the spleen. Except for this patient, no patients required a blood transfusion. The median operative time was 102 min (range 80-310 min), and the median estimated blood loss was 80 ml (range 30-800 ml). The median size of the mass in terms of the largest diameter was 4.7 cm (range 2.2-6.6 cm). There was no difference between pre- and postoperative median Female Sexual Function Index (FSFI) total scores (P = 0.102). All the patients except the one who had conversion to open surgery were very satisfied with the cosmetic result. CONCLUSIONS: The findings show TNLA to be a feasible and effective surgical technique that results in excellent cosmesis. It may be an alternative technique for the treatment of properly selected female patients with adrenal tumor.

A one-port pneumovesicum method in en bloc laparoscopic nephroureterectomy with bladder cuff resection is feasible and safe for upper tract transitional cell carcinoma.

OBJECTIVE: • To introduce a modified method for managing the distal ureter in laparoscopic nephroureterectomy (LNU) for upper tract transitional cell carcinoma (TCC) and to evaluate the feasibility and safety of this method. PATIENTS AND METHODS: • Six consecutive patients underwent LNU using a one-port pneumovesicum method for pathologically confirmed upper tract TCC. • Each patient was placed on the operating table in the lithotomy position and the pneumovesicum method was applied with CO(2) insufflation. Dissection was performed circumferentially through the entire detrusor muscle to disconnect the ureter from the bladder wall. A 10-mm trocar was placed into the bladder above the pubic bone. The distal ureter was occluded using a Hem-o-lok clip and pushed out of the bladder. Laparoscopic nephroureterectomy was then performed with the patient in the lateral position. • After surgery, all six patients received systemic chemotherapy and follow-up. RESULTS: • All procedures were performed successfully. • The median (range) operating time for the complete procedure was 105 (85-140) min, and the median (range) estimated blood loss was 125 (60-230) mL. • Seven days after surgery, each patient underwent cystography, which confirmed no extravasation of urine. • None of the patients developed bladder tumour recurrence or metastatic disease during follow-up. CONCLUSIONS: • The one-port pneumovesicum method in LNU, which is applied to manage the distal ureter and bladder cuff, is technically feasible and safe. • The method simplifies management of the distal ureter, reduces the invasiveness of the procedure and improves cosmesis.

[Sperm retrieval and the predictive parameter of non-obstructive azoospermia: a meta-analysis of literatures 1990 to 2008].

OBJECTIVE: To investigate which sperm retrieval technique is suitable for the non-obstructive azoospermia (NOA) patient, and to identify the relevant predictive parameters. METHODS: Literatures on NOA patients who had undergone sperm retrieval and pathological examination of testis were identified from Cochrane Library, CNKI and Medline (1990 to 2008) and analyzed. RESULTS: Twenty-five articles were enrolled. When testicular fine needle aspiration (TEFNA) was compared with testicular sperm extraction (TESE), the sperm retrieval rate of the former was 23.0%, significantly lower than that of the latter (52.2%, RR: 0.49, 95%CI: 0.41 - 0.60, P < 0.05); and when TESE was compared with micro-surgical testicular sperm extraction (mTESE), the sperm retrieval rate of the former was 35.7%, significantly lower than that of the latter (54.6%, RR: 0.70, 95%CI: 0.50 - 0.98, P < 0.05). Sperm retrieval rate was closely correlated with the testicular pathological category of the NOA patients. The sperm retrieval rates of the patients with hypospermatogenesis (HS), maturation arrest (MA), and Sertoli cell only syndrome (SCOS) were 76.7%, 46.2%, and 32.8% respectively (RR: 1.65, 2.40, 1.50; 95%CI: 1.21 - 2.91, 1.85 - 6.90, 1.02 - 2.26, P < 0.05). CONCLUSION: mTESE is the best sperm retrieval technique. A better to choice before deciding the treatment program of NOA patients is to identify the testicular pathological category in the NOA patients, and then to predict the outcome of TESE before assisted reproduction technology.