[Long-term survival analysis of 1 367 patients treated with radical nephrectomy from a single center].

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.

[Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy].

Objectives: To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Methods: The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging (M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results: The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney (ß=0.383, 95%CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time (ß=0.046, 95%CI:-0.383 to 0.475, P=0.831). Conclusion: In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.

Remimazolam dosing for intraoperative sedation in elderly patients undergoing hip replacement with combined spinal-epidural anesthesia.

OBJECTIVE: The aim of the study was to investigate the 50% and 95% effective doses (ED50 and ED95) of remimazolam for intraoperative sedation in elderly patients undergoing hip replacement with combined spinal-epidural anesthesia (CSEA). PATIENTS AND METHODS: We retrospectively analyzed the clinical data of 50 patients who underwent hip replacement with CSEA in our hospital from October 2021 to June 2022. There were 29 males and 21 females, aged 60-80 years old, with body mass indexes (BMI) ranging from 18 to 24 kg/m2, and American Society of Anesthesiologists (ASA) classifications of I or II. The modified Dixon sequential method was used to determine the dose of remimazolam for each patient. Each patient's initial dose was 0.1 mg/kg/h, and the dose gradient was 0.01 mg/kg/h. The bispectral index (BIS) and the modified observer's assessment of alertness/sedation score (MOAA/S) were used to evaluate the sedation of the patient. An MOAA/S score ≤3 and a BIS <85 at three or more time points during surgery indicated the sedation was satisfactory. The induction dose of the next patient was adjusted by 0.01 mg/kg/h based on the level of sedation achieved, and the study was terminated after eight crossovers. RESULTS: The ED50 and ED95 of remimazolam for sedation of elderly patients undergoing hip replacement with CSEA are 0.212 mg/kg/h (95% CI: 0.121-0.231 mg/kg/h) and 0.288 mg/kg/h (95% CI: 0.254-0.884 mg/kg/h), respectively. Two patients experienced transient bradycardia, five experienced hypoxemia, three experienced postoperative nausea, and three experienced postoperative delirium. No patients experienced adverse reactions such as injection pain, hypotension, vomiting, delayed awakening, or emergence agitation. CONCLUSIONS: The ED50 and ED95 of remimazolam for sedation of elderly patients undergoing hip replacement with CSEA are 0.212 mg/kg/h and 0.288 mg/kg/h, respectively.

[Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy].

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

[Characteristics and microRNA expression profile of exosomes derived from odontogenic dental pulp stem cells].

OBJECTIVE: To investigate the characteristics of exosomes derived from dental pulp stem cells (DPSCs) in the direction of odontogenic differentiation, to analyze the differences in microRNA expression profile between exosomes derived from undifferentiated and odontogenic DPSCs, and to analyze their possible signal transduction pathways. METHODS: (1) DPSCs were cultured in α minimum Eagle' s medium (α-MEM), and odontogenic DPSCs were cultured in odontogenic differentiation medium for 21 days, using alizarin red staining and alkaline phosphatase staining to identify the odontogenic differentiation. Exosomes from the cell supernatant were isolated respectively, named as dental pulp stem cells-exosomes (DPSCs-Exo) and dental pulp stem cells-odontogenic-exosomes (DPSCs-OD-Exo). The exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. (2) The microRNA expression profiles of DPSCs-Exo and DPSCs-OD-Exo were investigated by microRNA microarray. To validate the result of the microRNA microarray, real-time quantitative polymerase chain reaction (real-time PCR) assay was applied on 3 most significantly differential expressed microRNA. Pathway analysis was taken to detect enriched pathways associated with the predicted target genes of microRNA. RESULTS: (1) The DPSCs were isolated and cultured in vitro showed typical fibroblast-like morphology. The odontogenic differentiated DPSCs were spindle-shaped, polygonal, and uniform in size. Odontogenic differentiation group showed a large number of dark deposits in alizarin red staining and the cells were darkly stained in alkaline phosphatase staining, while the cells in normal culture medium group did not show obvious dyeing. The DPSCs-Exo and DPSCs-OD-Exo had the same morphology, both showed bilayer membrane and cup-shape. The peak sizes of DPSCs-Exo and DPSCs-OD-Exo were (114.67±9.07) nm and (134.00±8.54) nm, respectively. The difference between the two was statistically significant. DPSCs-Exo and DPSCs-OD-Exo both expressed the markers of exosomes, tumor susceptibility gene (TSG)101 and CD63. (2) microRNA microarray results showed that the expression profiles of DPSCs-Exo and DPSCs-OD-Exo were different. Nineteen increased by more than two times, and one decreased by 64%. Real-time PCR results showed that the expression levels of microRNA-1246, microRNA-1246-100-5p and microRNA-1246-494-3p in DPSCs-OD-Exo were significantly up-regulated. The difference was statistically significant. microRNA target prediction database and gene signaling pathway database were used to analyze differentially expressed microRNA, and it was predicted that differentially expressed microRNA could target axis inhibition protein 2(AXIN2) gene and Wnt/ß-catenin signaling pathway. CONCLUSION: DPSCs-OD-Exo and DPSCs-Exo had differences in their microRNA expression profile. Those differentially expressed microRNA may be involved in the regulation of DPSCs odontogenic differentiation.

[Prediction of 1p/19q codeletion status in diffuse lower-grade glioma using multimodal MRI radiomics].

OBJECTIVE: To develop a noninvasive method for prediction of 1p/19q codeletion in diffuse lower-grade glioma (DLGG) based on multimodal magnetic resonance imaging (MRI) radiomics. METHODS: We collected MRI data from 104 patients with pathologically confirmed DLGG between October, 2015 and September, 2022. A total of 535 radiomics features were extracted from T2WI, T1WI, FLAIR, CE-T1WI and DWI, including 70 morphological features, 90 first order features, and 375 texture features. We constructed logistic regression (LR), logistic regression least absolute shrinkage and selection operator (LRlasso), support vector machine (SVM) and Linear Discriminant Analysis (LDA) radiomics models and compared their predictive performance after 10-fold cross validation. The MRI images were reviewed by two radiologists independently for predicting the 1p/19q status. Receiver operating characteristic curves were used to evaluate classification performance of the radiomics models and the radiologists. RESULTS: The 4 radiomics models (LR, LRlasso, SVM and LDA) achieved similar area under the curve (AUC) in the validation dataset (0.833, 0.819, 0.824 and 0.819, respectively; P>0.1), and their predictive performance was all superior to that of resident physicians of radiology (AUC=0.645, P=0.011, 0.022, 0.016, 0.030, respectively) and similar to that of attending physicians of radiology (AUC=0.838, P>0.05). CONCLUSION: Multiparametric MRI radiomics models show good performance for noninvasive prediction of 1p/19q codeletion status in patients with in diffuse lower-grade glioma.

[Oligonucleotide drugs and their progress in stomatology].

Oligonucleotide drugs have the characteristics of targeting, modifiability and high biosafety. Recent studies have shown that oligonucleotide can be used to make biosensors, vaccine adjuvants, and has the functions of inhibiting alveolar bone resorption, promoting jaw and alveolar bone regeneration, anti-tumor, destroying plaque biofilm, and precise control of drug release. Therefore, it has a broad application prospect in the field of stomatology. This article reviews the classification, action mechanism and research status of oligonucleotide in stomatology. The aim is to provide ideas for further research and application of oligonucleotide.

[Oligonucleotide drugs and their progress in stomatology].

Oligonucleotide drugs have the characteristics of targeting, modifiability and high biosafety. Recent studies have shown that oligonucleotide can be used to make biosensors, vaccine adjuvants, and has the functions of inhibiting alveolar bone resorption, promoting jaw and alveolar bone regeneration, anti-tumor, destroying plaque biofilm, and precise control of drug release. Therefore, it has a broad application prospect in the field of stomatology. This article reviews the classification, action mechanism and research status of oligonucleotide in stomatology. The aim is to provide ideas for further research and application of oligonucleotide.

Dietary Total Antioxidant Capacity and Cognitive Function in Older Adults in the United States: The NHANES 2011-2014.

OBJECTIVES: Oxidative stress level takes part in the development of cognitive decline. However, the association between total antioxidant capacity (TAC) from diet and cognitive function is controversial. The aim of this study was to investigate the relationship between TAC and the cognitive function of older adults in the U.S. DESIGN: A cross-sectional study. SETTING: National Health and Nutrition Examination Surveys database. PARTICIPANTS: 2712 older adults aged over 60 years. MEASUREMENTS: TAC was calculated from 8 antioxidative vitamins based on the reference values for vitamin C equivalent antioxidant capacity obtained from individuals' 24 h dietary recall. Four memory-related assessments were employed [Immediate Recall test (IRT), Delayed Recall test (DRT), Animal Fluency test (AFT), and Digit Symbol Substitution test (DSST)]. RESULTS: Among the 2712 participants, the median age was 68 years, and 50.4% were women. Participants in the group with higher TAC levels had relatively higher IRT, AFT and DSST scores (P=0.025, P=0.008, P<0.001, respectively). In adjusted weighted linear regression, log-transformed TAC was positively associated with AFT (ß=1.10, 95%CI: 0.51, 1.70) and DSST (ß=2.81, 95%CI: 1.16, 4.45). Compared with the first quartile, the participants in the second (Q2 vs. Q1, OR=0.66, 95%CI: 0.43,1.02) and fourth quartile (Q4 vs. Q1, OR=0.47, 95%CI:0.28, 0.78) of log-transformed TAC showed a decreased risk of impaired cognitive function (ICF) after adjusting for confounders. The dose-response analysis indicated a gradual descent in the risk of ICF as TAC increases. Diabetes mellitus (DM) mediated part of the effect of TAC on ICF. The relationship between TAC and ICF was more pronounced in subjects with DM (Q4 vs Q1, OR=0.36, 95%CI:0.17, 0.74). CONCLUSION: Our findings support that higher dietary antioxidant potential was related to a decreased risk of cognitive dysfunction, particularly in the subjects with DM who may have oxidative injury. DM was one of the factors mediating the effect of TAC on ICF.

[Preliminary experience of gasless transoral vestibular robotic thyroidectomy].

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

A modified Child-Turcotte-Pugh score based on plasma ammonia predicts survival for patients with decompensated cirrhosis.

BACKGROUND: Plasma ammonia has been shown to be an independent prognostic factor for patients with liver cirrhosis. AIM: We aimed to investigate the discrimination and calibration of a new prognostic model (aCTP) based on plasma ammonia (Amm) replacing hepatic encephalopathy (HE) in the Child-Turcotte-Pugh (CTP) score. DESIGN: Diagnostic test, paired design. METHODS: Baseline Amm levels were corrected to the upper limit of normal (Amm-ULN). We designed the new model based on the cut-off value of Amm-ULN in the observational cohort of 554 clinically stable cirrhotic patients from January 2012 to July 2019. External validation was carried out using prospective data from 185 patients with liver cirrhosis. RESULTS: Our analysis showed that each 1-point increase in Amm-ULN was associated with a 2-fold increase in the likelihood of mortality [hazard ratio (HR), 2.06; 95% CI: 1.81-2.36, P < 0.001]. In the aCTP score, Amm-ULN < 1.0 was defined as a score of 1, 1.0 ≤ Amm-ULN < 1.4 as 2 and ≥1.4 as 3. The survival curves among three aCTP grades were significantly different (P < 0.0001). The aCTP score showed the better agreements between predicted and observed events in the validating cohorts than the CTP score (C-statistics: 0.75 and 0.69, P < 0.001). The aCTP score showed inspiring power to predict acute decompensation (C-statistics: 0.76; 95% CI: 0.71-0.81) and acute-on-chronic liver failure (C-statistics: 0.81; 95% CI: 0.77-0.86). CONCLUSION: This study demonstrates the feasibility and the potential for plasma Amm replacing HE (aCTP) to enhance the prognostication of transplant-free survival provided by the CTP score for patients with decompensated cirrhosis.

[Efficacy of partial nephrectomy in patients with localized renal carcinoma: a 20-year experience of 2 046 patients in a single center].

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Radiomics signature based on CECT for non-invasive prediction of response to anti-PD-1 therapy in patients with hepatocellular carcinoma.

PURPOSE: This study aimed to develop a radiomics signature (RS) based on contrast-enhanced computed tomography (CECT) and evaluate its potential predictive value in hepatocellular carcinoma (HCC) patients receiving anti-PD-1 therapy. METHOD: CECT scans of 76 HCC patients who received anti-PD-1 therapy were obtained in this study (training group = 53 and validation group = 23). The least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics features of primary and metastatic lesions and establish a RS to predict lesion-level response. Then, a nomogram combined the mean RS (MRS) and clinical variables with patient-level response as the end point. RESULTS: In the lesion-level analysis, the area under the curves (AUCs) of RS in the training and validation groups were 0.751 (95% CI, 0.668-0.835) and 0.734 (95% CI, 0.604-0.864), respectively. In the patient-level analysis, the AUCs of the nomogram in the training and validation groups were 0.897 (95% CI, 0.798-0.996) and 0.889 (95% CI, 0.748-1.000), respectively. The nomogram stratified patients into low- and high-risk groups, which showed a significant difference in progression-free survival (PFS) (p<0.05). CONCLUSIONS: The RS is a noninvasive biomarker for predicting anti-PD-1 therapy response in patients with HCC. The nomogram may be of clinical use for identifying high-risk patients and formulating individualised treatments.

Osteocalcin reduces fat accumulation and inflammatory reaction by inhibiting ROS-JNK signal pathway in chicken embryonic hepatocytes.

Osteocalcin (OCN) has a function in preventing fatty liver hemorrhagic syndrome (FLHS) in poultry. The aim of this study was to investigate the effects of OCN on fat emulsion stimulated chicken embryonic hepatocytes and related signaling pathways. The primary chicken embryonic hepatocytes were isolated from the incubated 15-day (E15) pathogen free eggs and cultured with dulbecco's modified eagle medium (DMEM). After the hepatocyte density reached 80%, the cells were divided into 5 groups: control group (CONT), fat emulsion group (FE, 10% FE, v/v), FE with ucOCN at 1 ng/mL (FE-LOCN), 3 ng/mL (FE-MOCN), and 9 ng/mL (FE-HOCN). In addition, 2 mM N-Acetyl-L-cysteine (NAC) a reactive oxygen species (ROS) scavenger, and 5 µM SP600125, a Jun N-terminal kinase (JNK) inhibitor, were added separately in to the DMEM with 10% FE to test effects of FE on the function of ROS-JNK signal pathway. The number of hepatocytes, cell ultra-microstructure, viability, and apoptosis were detected after 48 h treatment, and the protein expressions and enzyme concentrations were detected after 72 h treatment. The results showed that, compared to the control group, FE increased the triglyceride (TG) concentration and lipid droplets (LDs) in chicken embryonic hepatocytes (P < 0.05), and induced hepatocytic edema with obviously mitochondrial swelling, membrane damage, and cristae rupture. FE also decreased ATP concentration, increased ROS concentrations and mitochondrial DNA (mtDNA) copy number, promoted inflammatory interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α) concentrations and hepatocytic apoptosis rate, and raised phospho-c-Jun N-terminal kinase (p-JNK) protein expressions. Compared to the FE group, ucOCN significantly increased hepatocyte viability, reduced hepatocytic TG concentrations and LDs numbers, and alleviated hepatocytic edema and mitochondrial swelling. Furthermore, ucOCN significantly decreased ROS concentrations, increased ATP concentrations, reduced IL-1, IL-6, TNF-α concentrations and hepatocytic apoptosis rate, and inhibited p-JNK protein expressions (P < 0.05). NAC had the similar functions of ucOCN reduced the ROS concentration and inhibited the TNF-α protein expression and p-JNK/JNK ration. Similarly, SP600125 reduced p-JNK/JNK protein expression, IL-1, IL-6, TNF-α, and TG concentrations without effects on ROS concentration and hepatocytic apoptosis. These results suggest that ucOCN alleviates FE-induced mitochondrial damage, cellular edema, and apoptosis of hepatocytes. These results reveal that the functions of ucOCN in reducing fat accumulation and inflammatory reaction in chicken embryonic hepatocytes are mostly via inhibiting the ROS-JNK signal pathway.

Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study.

OBJECTIVE: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration. PATIENTS AND METHODS: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators. RESULTS: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol. CONCLUSIONS: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

Clinical efficacy of targeted therapy, immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX), and lipiodol embolization in the treatment of unresectable hepatocarcinoma.

To evaluate the clinical efficacy of targeted therapy and immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX and lipiodol embolization in the treatment of unresectable hepatocellular carcinoma. Patients included in the study were those who received targeted therapy and immunotherapy combined with HAIC of FOLFOX and lipiodol embolization in Zhongshan People's Hospital from December 2020 to June 2021 for unresectable hepatocellular carcinoma. Evaluation indicators included objective response rate (ORR), median progression-free survival (mPFS), median duration of response (mDOR), 1-year overall survival rate (OS), surgical conversion rate, and adverse events. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors (mRECIST and RECIST v1.1). A total of 35 patients were included in this study, 30 of whom completed treatment evaluation. According to mRECIST evaluation criteria, the objective response rate (ORR) was 83.3% (25/30); the complete response (CR) was 60% (18/30); the partial response (PR) was 23.3% (7/30), and stable disease (SD) was 16.7% (5/30). The mDOR was 10.3 months (95% Cl: 8.27-NE), and the mPFS was 13.2 months (95% CI: 10.3-NE); the surgical conversion rate was 30.0% (9/30). The 1-year OS was 96.7%. There were no serious surgical complications and grade 4 or 5 adverse events of targeted therapy, immunotherapy and HAIC. Some patients had grade 3 adverse reactions in gastrointestinal toxicity or hepatotoxicity, and the adverse reactions were improved after corresponding symptomatic treatment. We concluded that HAIC of FOLFOX and lipiodol embolization combined with targeted therapy and immunotherapy had a significant curative effect in the treatment of unresectable hepatocellular carcinoma, with no serious adverse reactions and a high rate of surgical conversion rate.

Development of a prognostic prediction model for patients with cutaneous malignant melanoma: a study based on the SEER database.

OBJECTIVE: To investigate the prognostic factors of cutaneous malignant melanoma (CMM) and establish an effective nomogram survival prediction model. MATERIALS AND METHODS: The clinical data of patients diagnosed with stage M0 CMM from 2000 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database were collected and retrospectively analyzed. The variables that may be related to prognosis were analyzed by Lasso-Cox regression analysis using R software. Independent prognostic factors were screened. A nomogram model for predicting the prognosis of CMMC was drawn, and its accuracy was verified by c-index, NR, IDI and calibration curve. RESULTS: A total of 2,679 patients with CMM were included. Lasso-Cox analysis showed that male sex, multiple tumors, higher T stage, SEER stage, widowed, divorced, and separated often indicated poor prognosis. The nomogram model calibration curve was in good agreement with the ideal curve, and the C-index was 0.734 in the training group and 0.761 in the validation group, respectively. In the training group, the AUC of 1-, 3-, 5- and 8-year survival were 0.80, 0.75, 0.74 and 0.72, respectively. In the validation group, the AUC of 1-, 3-, 5- and 8-year survival were 0.75, 0.79, 0.78 and 0.79, respectively. NRI and IDI were superior to the prediction ability of TNM stage and SEER stage (p < 0.05). The established prognostic score can divide patients into high and low score groups with significant prognostic difference (p < 0.05). CONCLUSIONS: Sex, SEER stage, T stage, total number of tumors and marital status are independent prognostic factors for CMM patients, and the nomogram model presented a better performance than TNM stage and SEER stage in predicting the prognosis of CMM patients.