Objective: To explore the safety and feasibility of the disconnection of the left renal artery preferentially during robot-assisted inferior vena cava (IVC) thrombectomy for patients with left renal cell carcinoma and tumor emboli. Methods: Clinical data of 7 patients who underwent robot-assisted IVC thrombectomy and radical nephrectomy in the First Affiliated Hospital of Zhengzhou University during Dec.2021 and Oct.2024 were retrospectively analyzed.Thrombectomy was performed first，followed by nephrectomy. The “IVC-first, kidney-last”robotic technique was developed to minimize chances of IVC thrombus. When patients in left lateral decubitus position, the left renal artery was severed from the right side through the inferior vena cava and abdominal aorta. After removal of thrombus from IVC was completed, patients changed to the right lateral position to complete radical left nephrectomy. Results: Imaging examinations revealed that the median diameter of the renal cell carcinomas was 83(46-99) mm; the median length of the inferior vena cava cancerous emboli was 49(2-91) mm.According to the Mayo classification，the cancerous emboli were gradeⅠ in 2 cases，gradeⅡ in 4 cases，and grade Ⅲ in 1 case.All surgeries were successful.The median operation time was 248(201-331) minutes，blood loss 500(200-1000) mL，and 6 cases required intraoperative blood transfusion.The median time for transition into the intensive care unit was 1(1-4) days，and drainage tube removal 6(5-12) days.Serum creatinine increased significantly in 5 cases，4 of which returned to normal after 1 week，but 1 had renal insufficiency (creatinine 166 μmol/L).Chylous fistula occurred in 1 patient，and lower extremity venous thrombosis developed in 3 patients.Pathological examinations indicated 6 cases of renal cell carcinoma and 1 case of MiT family translocation renal cell carcinoma.During the median follow-up of 17(1-35) months，5 cases were tumor-free，while 2 had lung and retroperitoneal metastases.They received targeted therapy of axitinib combined immunotheraphy and lived with tumors. Conclusion: In the left lateral position for left renal cell carcinoma with cancerous emboli，robot-assisted laparoscopic thrombectomy by crossing the inferior vena cava and abdominal aorta and disconnecting the left renal artery first is safe and feasible.

Objective:To investigate the effects of microRNA (miR) -125b on the proliferation and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway of hepatocellular carcinoma (HCC) cell by targeting Polo like kinases (PLK4).Methods:The tumor tissues and adjacent tissues of 65 patients with HCC were collected from March 2022 to March 2023 in Tianjin Medical University Cancer Hospital, including 33 males and 32 females, aged (60.1±5.6) years. The expressions of miR-125a and miR-125b in liver cancer, adjacent tissues and liver cancer cells were detected by fluorescence quantitative polymerase chain reaction. Low expression liver cancer cell was selected to transfect negative control (NC) sequences of miR, miR-125a and miR-125b. Subsequently, miR-NC and NC plasmid, miR-125b sequence and NC plasmid, and miR-125b sequence and PLK4 plasmid were co-transfected. Cell proliferation was detected by cell counting assay, the expression of PLK4, phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) was detected by Western blot, and miR-125b-targeting PLK4 were detected by bioinformatics analysis and dual luciferase reporter gene.Results:The relative expressions of miR-125a and miR-125b in HCC patients were (0.62±0.08) and (0.58±0.07), respectively, lower than those in adjacent tissues (1.00±0.12) and (1.00±0.13), and the differences were statistically significant ( t=21.24, 22.93, P=0.005, P<0.001). HepG2 cells with low expression of miR-125a and miR-125b and miR-125b targeting PI3K/Akt were selected for transfection. Bioinformatic analysis and dual luciferase reporter gene assay confirmed that miR-125b binds to PLK4. Overexpression of miR-125b could inhibit the proliferation of HepG2 cells and the expression of p-PI3K and p-Akt, while overexpression of PLK4 could partially reverse the proliferation inhibition caused by miR-125b and the expression of p-PI3K and p-Akt, (0.91±0.07) vs(0.41±0.04), (0.97±0.08) vs (0.32±0.03)( t=13.87, 17.01, both P<0.001). Conclusion:The inhibitory effect of miR-125b on HepG2 cell proliferation and PI3K/Akt signaling pathway is partly mediated by targeted inhibition of PLK4.

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. Materials and Methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2′-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Conclusions Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Atoh1 gene encodes a helix-loop-helix transcription factor which is involved in the generation and differentiation of mammalian auditory hair cells and supporting cells, and regulation of the proliferation of cochlear cells, therefore plays an important role in the pathogenesis and recovery of sensorineural deafness. This study reviews the progress of the Atoh1 gene in hair cell regeneration, with the aim of providing a reference for the study of hair cell regeneration gene therapy for sensorineural deafness.
Animals ; Humans ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Hair Cells, Auditory/physiology* ; Transcription Factors ; Hearing Loss, Sensorineural ; Cell Differentiation ; Deafness ; Regeneration/genetics* ; Mammals

Objective:To construct a prognosis associated micro RNA(miRNA) prediction model based on bioinformatics analysis and evaluate its application value in pancreatic cancer patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 171 pancreatic cancer patients from the Cancer Genome Atlas (TCGA) (https: //cancergenome.nih.gov/) between establishment of database and September 2017 were collected. There were 93 males and 78 females, aged from 35 to 88 years, with a median age of 65 years. Of the 171 patients, 64 had complete clinicopathological data. Patients were allocated into training dataset consisting of 123 patients and validation dataset consisting of 48 patients using the random sampling method, with a ratio of 7∶3. The training dataset was used to construct a prediction model, and the validation dataset was used to evaluate performance of the prediction model. Nine pairs of miRNA sequencing data (GSE41372) of pancreatic cancer and adjacent tissues were downloaded from Gene Expression Omnibus database. The candidate miRNAs were selected from differentially expressed miRNAs in pancreatic cancer and adjacent tissues for LASSO-COX regression analysis based on the patients of training dataset. A prognosis associated miRNA prediction model was constructed upon survival associated miRNAs which were selected from candidate differentially expressed miRNAs. The performance of prognosis associated miRNA prediction model was validated in training dataset and validation dataset, the accuracy of model was evaluated using the area under curve (AUC) of the receiver operating characteristic curves and the efficiency was evaluated using the consistency index (C-index). Observation indicarors: (1) survival of patients; (2) screening results of differentially expressed miRNAs; (3) construction of prognosis associated miRNA model; (4) validation of prognosis associated miRNA model; (5) comparison of clinicopathological factors in pancreatic cancer patients; (6) analysis of factors for prognosis of pancreatic cancer patients; (7) comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging. Measurement data with normal distribution were represented as Mean± SD, comparison between groups was analyzed by the student- t test, and comparison between multiple groups was analyzed by the AVONA. Measurement data with skewed data were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Ordinal data were analyzed using the rank sum test. Correlation analysis was conducted based on count data to mine the correlation between prognosis associated miRNA model and clinicopathological factors. COX univariate analysis and multivariate analysis were applied to evaluate correlation with the results described as hazard ratio ( HR) and 95% confidence interval ( CI). HR<1 indicated the factor as a protective factor, HR>1 indicated the factor as a risk factor, and HR equal to 1 indicated no influence on survival. The Kaplan-Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Survival of patients: 123 patients in the training dataset were followed up for 31-2 141 days, with a median follow-up time of 449 days. The 3- and 5-year survival rates were 16.67% and 8.06%. Forty-eight patients in the validation dataset were followed up for 41-2 182 days, with a median follow-up time of 457 days. The 3- and 5-year survival rates were 15.63% and 9.68%. There was no significant difference in the 3- or 5-year survival rates between the two groups ( χ2=0.017, 0.068, P>0.05). (2) Screening results of differentially expressed miRNAs. Results of bioinformatics analysis showed that 102 candidate differentially expressed miRNAs were selected, of which 63 were up-regulated in tumor tissues while 39 were down-regulated. (3) Construction of prognosis associated miRNA model: of the 102 candidate differentially expressed miRNAs, 5 survival associated miRNAs were selected, including miR-21, miR-125a-5p, miR-744, miR-374b, miR-664. The differential expression patterns of pancreatic cancer to adjacent tissues were up-regulation, up-regulation, down-regulation, up-regulation, and down-regulation, respectively, with the fold change of 4.00, 3.43, 3.85, 2.62, and 2.35. A prognostic expression equation constructed based on 5 survival associated miRNAs = 0.454×miR-21 expression level-0.492×miR-125a-5p expression level-0.49×miR-744 expression level-0.419×miR-374b expression level-0.036×miR-664 expression level. (4) Validation of prognosis associated miRNA model: The C-index of prognosis associated miRNA model was 0.643 and 0.642 for the training dataset and validation dataset, respectively. (5) Comparison of clinicopathological factors in pancreatic cancer patients: results of COX analysis showed that the prognosis associated miRNA model was highly related with pathological T stage and location of pancreatic cancer ( Z=45.481, χ2=10.176, P<0.05). (6) Analysis of factors for prognosis of pancreatic cancer patients: results of univariate analysis showed that pathological N stage, radiotherapy, molecular targeted therapy, score of prognosis associated miRNA model were related factors for prognosis pf pancreatic cancer patients ( HR=2.471, 0.290, 0.172, 2.001, 95% CI: 1.012-6.032, 0.101-0.833, 0.082-0.364, 1.371-2.922, P<0.05). Results of multivariate analysis showed that molecular targeted therapy was an independent protective factor for prognosis of pancreatic cancer patients ( HR=0.261, 95% CI: 0.116-0.588, P<0.05) and score of prognosis associated miRNA model≥1.16 was an independent risk factor for prognosis of pancreatic cancer patients ( HR=1.608, 95% CI: 1.091-2.369, P<0.05). (7) Comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging: in the training dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.671, -1.867, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging for 3- and 5-year survival prediction was 0.797, 0.935 and 0.737 , 0.703, with the 95% CI of 0.622-0.972, 0.828-1.042 and 0.571-0.904 , 0.456-0.951. The C-index was 0.643 and 0.534. In the validation dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.729, -1.923, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging was 0.750, 0.873 and 0.721 , 0.703, with the 95% CI of 0.553-0.948, 0.720-1.025 and 0.553-0.889, 0.456-0.950, respectively. The C-index was 0.642 and 0.544. Conclusions:A prognosis associated miRNA prediction model can be constructed based on 5 survival associated miRNAs in pancreatic cancer patients, as a complementation to current TNM staging and other clinicopathological parameters, which provides individual and accurate prediction of survival for reference in the clinical treatment.

Objective:To study the survival outcomes in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) treated with sorafenib combined with transcatheter arterial chemoembolization (TACE) versus sorafenib alone.Methods:The data of 92 patients with BCLC stage C HCC at Tianjin Medical University Cancer Institute& Hospital from January 2008 to December 2015 were retrospectively studied. There were 82 males and 10 females. The average age was 56.3 years. Classified according to whether there were vascular invasion and/or distant metastasis, patients were divided into the vascular invasion group ( n=24), the metastasis group ( n=48), and the vascular invasion combined with metastasis group ( n=20). All patients were treated with sorafenib, but some patients received combined treatment with TACE. The survival data of these patients on follow-up was collected. The Kaplan-Meier method was used for survival analysis, and the survival rates were compared by the log-rank test. Univariate and multivariate Cox analyses were used to determine the prognostic factors of patients’ survival. Results:There were no significant differences in the baseline clinical data among the three groups (all P>0.05). Multivariate Cox regression analysis showed that pre-treatment alpha fetal protein >20 μg/L ( HR=1.90, 95% CI: 1.13-3.12), alkaline phosphatase >125 U/L ( HR=1.60, 95% CI: 1.03-2.49) and sorafenib alone ( HR=2.11, 95% CI: 1.23-3.54) were independent risk factors of survival for these patients. There were no significant differences in the cumulative survival rates among the three groups ( P>0.05). In the vascular invasion group, the cumulative survival rates of patients treated with combined sorafenib and TACE ( n=4) were significantly higher than those treated with sorafenib alone ( n=20) ( P<0.05). Conclusion:Compared with sorafenib alone, sorafenib combined with TACE resulted in better prognosis for patients with BCLC stage C HCC. Subgroup analysis showed that patients with vascular invasion had significantly better survival treated with combined sorafenib and TACE than sorafenib alone.

Objective: To evaluate the safety and efficacy of surgical treatment after neoadjuvant chemotherapy (NCT) for patients with cT4N+ colon cancer, and to explore whether the indication of NCT for colon cancer can be extended from cT4b to cT4N+ . Methods: The clinical data of 40 patients with cT4N+ colon cancer who underwent neoadjuvant chemotherapy followed by surgical treatment was retrospectively analyzed. The safety of neoadjuvant chemotherapy, surgical complications, R0 resection rate, tumor regression grade and prognosis were evaluated. Results: Of the 40 patients, 23 were male and 17 were female; the median age was 57 years old. All patients were well tolerated with chemotherapy, and only one case (1/40, 2.5%) had grade 3 chemotherapy-related adverse event. They all underwent surgery after chemotherapy, and 95.0% (38/40) achieved microscopically clear resection (R0). Of the 11 patients with cT4b, 54.5% (6/11) had undergone multivisceral resection (MVR). Postoperative pathological results showed that 12 patients had moderate to severe tumor regression, including one(1/40, 2.5%) achieved pathologic complete response (pCR). 29(72.5%) and 22 (55.0%) patients achieved down-staging of tumor T stage and N stage, respectively. The occurrence of surgical complications was 22.5% (9/40), including one case of anastomotic leakage (1/40, 2.5%). The 3-year disease-free survival and overall survival of the whole group were 75.0% and 80.0%, respectively. Conclusion Surgery after neoadjuvant chemotherapy is safe and effective for patients with cT4N+ colon cancer, therefore indications for neoadjuvant chemotherapy for advanced colon cancer can be extended to cT4N+ stage.

Objective To compare the efficacy of radiofrequency ablation versus surgical resection in treatment of colorectal liver metastases with a maximum diameter ≤ 3 cm and a number ≤ 3, and to analyze the risk factors of recurrence. Methods The data of 97 patients with colorectal liver metastases from January 2012 to June 2016 treated at Tianjin Medical University Cancer Institute and Hospital were analyzed retrospectively. There were 66 males and 31 females. The patients were divided into the radiofre-quency ablation group (23 patients) and the surgical resection group ( 74 patients). The patients were followed up. The clinicopathological features of the two groups before treatment were compared. Kaplan-Meier curves were drawn, and the recurrence-free survival curve and overall survival curve of the two groups were compared by log-rank test. Univariate and multivariate Cox regression analysis was used to analyze the risk factors of recurrence. Results There were no significant differences in age, location of primary tumor, number and size of liver metastases, and preoperative carcinoembryonic antigen level between the two groups (P＞0. 05). On the date this study was censored, there were 50 patients who had developed recurrence in the surgical resection group and 22 patients in the ablation group, (67. 6% vs. 95. 7% ). The difference was significant (P＜0. 05). The 1-and 2-year recurrence-free survival rates were 54. 6% and 39. 0% in the surgical resection group and 39. 1% and 8. 7% in the radiofrequency ablation group, respectively. The difference was significant (P＜0. 05). There was no local recurrence in either of the two groups. There was no significant difference in the overall survival curves between the two groups (P＞0. 05). Univariate and multivariate analysis showed that N 1 ～2 staging (HR=1. 908, 95% CI: 1. 094～3. 325), simultaneous liver metastasis (HR=1. 662, 95% CI: 1. 024～2. 695) and radiofrequency ablation (HR=2. 708, 95% CI: 1. 589～4. 617) were independent risk factors of recurrence for colorectal liver metastasis. Conclusions Radiofrequency ablation can achieve complete ablation in patients with colorectal liver metastases with maximum diameter ≤3 cm and number≤3, but the recurrence rate of radiofrequency ablation is significantly higher than that of surgical resection. N 1 ～2 staging, simultaneous liver metastasis and radiofrequency ablation were independent risk factors for recurrence of colorectal liver metastasis.

Objective To evaluate the safety and efficacy of surgical treatment after neoadjuvant chemotherapy (NCT) for patients with cT4N+colon cancer, and to explore whether the indication of NCT for colon cancer can be extended from cT4b to cT4N+. Methods The clinical data of 40 patients with cT4N+colon cancer who underwent neoadjuvant chemotherapy followed by surgical treatment was retrospectively analyzed. The safety of neoadjuvant chemotherapy, surgical complications, R0 resection rate, tumor regression grade and prognosis were evaluated. Results Of the 40 patients, 23 were male and 17 were female; the median age was 57 years old. All patients were well tolerated with chemotherapy, and only one case (1／40, 2.5%) had grade 3 chemotherapy?related adverse event. They all underwent surgery after chemotherapy, and 95.0%(38／40) achieved microscopically clear resection (R0). Of the 11 patients with cT4b, 54.5%( 6／11) had undergone multivisceral resection ( MVR). Postoperative pathological results showed that 12 patients had moderate to severe tumor regression, including one ( 1／40, 2.5%) achieved pathologic complete response (pCR).29(72.5%) and 22 (55.0%) patients achieved down?staging of tumor T stage and N stage, respectively. The occurrence of surgical complications was 22.5%(9／40), including one case of anastomotic leakage (1／40, 2.5%). The 3?year disease?free survival and overall survival of the whole group were 75.0% and 80.0%, respectively. Conclusion Surgery after neoadjuvant chemotherapy is safe and effective for patients with cT4N+colon cancer, therefore indications for neoadjuvant chemotherapy for advanced colon cancer can be extended to cT4N+ stage.

Objective To evaluate the safety and efficacy of surgical treatment after neoadjuvant chemotherapy (NCT) for patients with cT4N+colon cancer, and to explore whether the indication of NCT for colon cancer can be extended from cT4b to cT4N+. Methods The clinical data of 40 patients with cT4N+colon cancer who underwent neoadjuvant chemotherapy followed by surgical treatment was retrospectively analyzed. The safety of neoadjuvant chemotherapy, surgical complications, R0 resection rate, tumor regression grade and prognosis were evaluated. Results Of the 40 patients, 23 were male and 17 were female; the median age was 57 years old. All patients were well tolerated with chemotherapy, and only one case (1／40, 2.5%) had grade 3 chemotherapy?related adverse event. They all underwent surgery after chemotherapy, and 95.0%(38／40) achieved microscopically clear resection (R0). Of the 11 patients with cT4b, 54.5%( 6／11) had undergone multivisceral resection ( MVR). Postoperative pathological results showed that 12 patients had moderate to severe tumor regression, including one ( 1／40, 2.5%) achieved pathologic complete response (pCR).29(72.5%) and 22 (55.0%) patients achieved down?staging of tumor T stage and N stage, respectively. The occurrence of surgical complications was 22.5%(9／40), including one case of anastomotic leakage (1／40, 2.5%). The 3?year disease?free survival and overall survival of the whole group were 75.0% and 80.0%, respectively. Conclusion Surgery after neoadjuvant chemotherapy is safe and effective for patients with cT4N+colon cancer, therefore indications for neoadjuvant chemotherapy for advanced colon cancer can be extended to cT4N+ stage.