Auranofin Suppresses the Growth of Canine Mammary Tumour Cells and Induces Apoptosis via the PI3K/AKT Pathway.

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies.

Decoding sunitinib resistance in ccRCC: Metabolic-reprogramming-induced ABAT and GABAergic system shifts.

Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

Renal Angiomyolipoma with Tumor Thrombus in the Inferior Vena Cava and Right Atrium Accompanied by Renal Cell Carcinoma: A Case Report.

Background: Renal angiomyolipoma (AML) without local invasion is generally considered benign. However, it may extend to the renal sinus, even the renal vein, or the inferior vena cava (IVC). In patients with non-tuberous sclerosis complex, coexistence of renal cell carcinoma (RCC) and renal AML is uncommon. Case presentation: A 72-year-old woman was incidentally found to have a solitary right renal mass with an IVC thrombus extending into the right atrium during a routine health checkup. Robot-assisted laparoscopic radical nephrectomy and thrombectomy were successfully performed through adequate preoperative examination and preparation. Two tumor lesions were found and pathologically confirmed as renal AML and RCC, and the tumor thrombus was derived from the renal AML. During the one-year follow-up period, no signs of recurrence or metastatic disease were observed. Conclusions: Renal AML with a tumor thrombus in the IVC and right atrium accompanied by RCC may occur, although rarely. In clinical practice, if preoperative manifestations differ from those of common diseases, rare diseases must be considered to avoid missed diagnoses. In addition, adequate examination and multidisciplinary discussions before making a diagnosis are necessary. For a level 4 tumor thrombus with no infringement of the venous wall, adoption of robot-assisted minimally invasive surgery, without extracorporeal circulation technology, is feasible.

[Analysis of risk factors for long-term overactive bladder after radical prostatectomy].

OBJECTIVE: To analyze the incidence and progression of overactive bladder (OAB) symptoms following radical prostatectomy for prostate cancer patients and to identify related risk factors. METHODS: A retrospective study was conducted on 263 local stage prostate cancer patients who underwent radical prostatectomy at Peking University Third Hospital from January 2013 to May 2017. Clinical baseline information, comprehensive imaging features, perioperative parameters, preoperative urinary control status, pathological diagnosis, and the incidence of OAB within one year postoperatively were collected and analyzed. In the imaging features, two parameters were defined: Bladder wall thickness (BWT) and bladder mucosal smoothness (BMS), which were used to predict the occurrence of OAB. Patients were evaluated based on their clinical baseline characteristics, including age, body mass index (BMI), comorbidities, and prostate-specific antigen (PSA) levels. The imaging characteristics were assessed using preoperative MRI, focusing on BWT and BMS. Perioperative parameters included operative time, blood loss, and length of hospital stay. The OAB symptoms were assessed using the overactive bladder symptom score (OABSS) and the international prostate symptom score (IPSS). These scores were correlated with the postoperative incidence of OAB. RESULTS: Among the 263 patients who underwent radical prostatectomy, 52 (19.8%) exhibited OAB within one year postoperatively. Of the 40 patients with preoperative OAB symptoms, 17 (42.5%) showed remission postoperatively, while 23 (57.5%) had persistent symptoms. Additionally, 29 patients developed new-onset OAB, accounting for 55.77% of all postoperative OAB cases. Univariate analysis indicated that BWT, BMS, OABSS, and IPSS score were all associated with the occurrence of postoperative OAB. Further multivariate analysis identified BMS as an independent risk factor for long-term OAB (P < 0.001). CONCLUSION: Long-term postoperative overactive bladder is a common complication following radical prostatectomy. The findings suggest that preoperative MRI measurements of bladder wall thickness and bladder mucosal smoothness during bladder filling phase can predict the risk of OAB occurrence postoperatively. Identifying these risk factors preoperatively can help in counseling patients about potential complications and in developing strategies to mitigate the risk of developing OAB after surgery. Early detection and management of these parameters might improve the quality of life for patients undergoing radical prostatectomy.

[Prognostic factors of patients with muscle invasive bladder cancer with intermediate-to-high risk prostate cancer].

OBJECTIVE: To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer (MIBC) with intermediate-to-high-risk primary prostate cancer. METHODS: From January 2012 to October 2023, the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed. All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study. Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients. For significant influencing factors (pathological T stage, M stage and perineural invasion of bladder cancer), survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors. RESULTS: A total of 32 patients were included in this study. The mean age was (72.5±6.6) years; the median preoperative total prostate specific antigen (tPSA) was 6.68 (2.47, 6.84) µg/L; the mean preoperative creatinine was (95±36) µmol/L, and the median survival time was 65 months. The majority of the patients (87.5%) had high-grade bladder cancer, 53.1% had lymphatic invasion, and 31.3% had perineural invasion. Prostate involvement was observed in 25.0% of the cases, and the positive rate of soft-tissue surgical margin was 37.5%. Multivariate Cox analysis revealed that preoperative creatinine level (HR=1.02, 95%CI: 1.01-1.04), pathological stage of bladder cancer T3 (HR=11.58, 95%CI: 1.38-97.36) and T4 (HR=19.53, 95%CI: 4.26-89.52) metastasis of bladder cancer (HR=9.44, 95%CI: 1.26-70.49) and perineural invasion of bladder cancer (HR=6.26, 95%CI: 1.39-28.27) were independent prognostic factors (P < 0.05). Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3, T4, M1, and perineural invasion were unfavorable factors affecting the patients' survival prognosis (P < 0.05). CONCLUSION: Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis. High preoperative serum creatinine, T3 or T4 pathological stage of bladder cancer, metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

[Clinicopathological characteristics and prognosis of multilocular cystic renal neoplasm of low malignant potential].

OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of patients with multilocular cystic renal neoplasm of low malignant potential and compare the clinicopathological characteristics of patients with multilocular cystic renal neoplasm of low malignant potential who underwent different surgical methods. METHODS: Clinicopathological data and prognosis of patients admitted to Peking University Third Hospital from January 2010 to September 2023 were collected. Patients who underwent radical nephrectomy or nephron-sparing surgery and were pathologically diagnosed with multilocular cystic renal neoplasm of low malignant potential were identified. Based on the surgical methods, the patients were divided into radical nephrectomy group and nephron-sparing surgery group. The clinicopathological characteristics of the two groups were compared. RESULTS: A total of 35 patients were enrolled in this study. The median age at diagnosis was 53.0 (39.0-62.0) years. Among the 35 patients, 23 were males (65.7%) and 12 were females (34.3%). Nine patients underwent radical nephrectomy (25.7%), while 26 patients underwent nephron-sparing surgery (74.3%). The clinical T-stage of 35 patients did not exceed T2a stage. The median operation time was 145.0 min, and the median estimated intraoperative blood loss was 20.0 mL. The median postoperative hospitalization days was 6.0 d. The postoperative pathological results did not indicate renal sinus invasion, sarcomatous change, adrenal invasion or lymph node invasion. Based on the surgical methods, the patients were divided into a radical nephrectomy group and a nephron-sparing surgery group. There was no significant difference in clinicopathological charac-teristics between the two groups. Except for one patient who was lost to the follow-up, all the other patients were followed up for 8-111 months, with a median follow-up time of 70.5 months. Only one patient died from non-cancer-specific reasons, other patients had no tumor metastasis or recurrence. CONCLUSION: Patients with multilocular cystic renal neoplasm of low malignant potential have a good prognosis. There is no significant difference in clinicopathological characteristics of patients between nephron-sparing surgery group and radical nephrectomy group for multilocular cystic renal neoplasm of low malignant potential.

[Predicting the 3-year tumor-specific survival in patients with T3a non-metastatic renal cell carcinoma].

OBJECTIVE: To predict the 3-year cancer-specific survival (CSS) of patients with non-metastatic T3a renal cell carcinoma after surgery. METHODS: A total of 336 patients with pathologically confirmed T3a N0-1M0 renal cell carcinoma (RCC) who underwent surgical treatment at the Department of Urology, Peking University Third Hospital from March 2013 to February 2021 were retrospectively collected. The patients were randomly divided into a training cohort of 268 cases and an internal validation cohort of 68 cases at an 4 ∶ 1 ratio. Using two-way Lasso regression, variables were selected to construct a nomogram for predicting the 3-year cancer-specific survival (CSS) of the patients with T3aN0-1M0 RCC. Performance assessment of the nomogram included evaluation of discrimination and calibration ability, as well as clinical utility using measures such as the concordance index (C-index), time-dependent area under the receiver operating characteristic curve [time-dependent area under the curve (AUC)], calibration curve, and decision curve analysis (DCA). Risk stratification was determined based on the nomogram scores, and Kaplan-Meier survival analysis and Log-rank tests were employed to compare progression-free survival (PFS) and cancer-specific survival (CSS) among the patients in the different risk groups. RESULTS: Based on the Lasso regression screening results, the nomogram was constructed with five variables: tumor maximum diameter, histological grading, sarcomatoid differentiation, T3a feature, and lymph node metastasis. The baseline data of the training and validation sets showed no statistical differences (P>0.05). The consistency indices of the column diagram were found to be 0.808 (0.708- 0.907) and 0.903 (0.838-0.969) for the training and internal validation sets, respectively. The AUC values for 3-year cancer-specific survival were 0.843 (0.725-0.961) and 0.923 (0.844-1.002) for the two sets. Calibration curves of both sets demonstrated a high level of consistency between the actual CSS and predicted probability. The decision curve analysis (DCA) curves indicated that the column diagram had a favorable net benefit in clinical practice. A total of 336 patients were included in the study, with 35 cancer-specific deaths and 69 postoperative recurrences. According to the line chart, the patients were divided into low-risk group (scoring 0-117) and high-risk group (scoring 119-284). Within the low-risk group, there were 16 tumor-specific deaths out of 282 cases and 36 postoperative recurrences out of 282 cases. In the high-risk group, there were 19 tumor-specific deaths out of 54 cases and 33 post-operative recurrences out of 54 cases. There were significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) between the low-risk and high-risk groups (P < 0.000 1). CONCLUSION: A nomogram model predicting the 3-year CSS of non-metastatic T3a renal cell carcinoma patients was successfully constructed and validated in this study. This nomogram can assist clinicians in accurately assessing the long-term prognosis of such patients.

Comparison of cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant patients in chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by inflammation of the nasal and sinus mucosa. The inflammatory patterns may differ among patients, leading to different subtypes based on the dominant inflammatory cell type. This study aimed to compare the differences in cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant subtypes in patients with CRSwNP. METHODS: This study included 53 CRSwNP patients and 19 control subjects who did not have asthma or a history of cigarette smoking. The expression of cytokines and inflammatory cells was assessed via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. RESULTS: Among the cytokines analyzed, only IL-6 was significantly different between the two subtypes. A greater proportion of mast cells and IgE cells was present in plasma cell-dominant CRSwNP patients than in eosinophil-dominant group. For the three disease severity scores (LMK-CT, TPS and SNOT-22), objective scores (LMK-CT and TPS) were greater in the eosinophil-dominant CRSwNP group, while the opposite result was shown for the subjective score (SNOT-22). Additionally, the percentage of plasma cell-dominant cells was significantly positively correlated with disease severity according to the TPS and SNOT-22 scores. CONCLUSIONS: Our data revealed that plasma cell-dominant inflammation, a subtype of type 2 CRS, was significantly correlated with subjective disease severity. The study also highlights the role of IL-6, IgE and mast cells as distinguishing factors between eosinophil-dominant and plasma cell-dominant CRSwNP. This information could be useful for clinical diagnosis and personalized treatment.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.

Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

The Application of CT Radiomics in the Diagnosis of Vein Wall Invasion in Patients With Renal Cell Carcinoma Combined With Tumor Thrombus.

OBJECTIVE: The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy. MATERIALS AND METHODS: We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set. RESULTS: Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000). CONCLUSION: Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).

[Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy].

OBJECTIVE: Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters. METHODS: In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) µg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711). CONCLUSION: Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.

Minimally invasive, single-stage, multilevel surgery for obstructive sleep apnoea: A systematic review and meta-analysis.

OBJECTIVES: Minimally invasive, single-staged multilevel surgery (MISS MLS) could be an optimal treatment for selected patients with obstructive sleep apnea (OSA). We aim to systematically review the efficacy of MISS MLS for patients with OSA, as well as the clinical outcomes and possible complications in OSA patients before and after MISS MLS. DESIGN AND SETTING: Systematic review and meta-analysis. Six databases were searched, and the PRISMA guideline was followed. PARTICIPANTS: Patients with OSA receiving MISS MLS. MAIN OUTCOME MEASURES: The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of MISS MLS for OSA. Subgroup analyses and sensitivity analyses were also performed to identify the heterogeneity among the studies. RESULTS: There were initially 154 articles for identification. Eventually, six studies with a total of 848 OSA patients completely met the inclusion criteria and were further enrolled for analysis. The pooled analysis showed statistically significant lower AHI (apnea/hypopnea index, /hr.; mean difference: -8.931, 95% CI: -11.591 to -6.271, I2 = 87.4%), ESS (mean difference: -2.947, 95% CI: -4.465 to -1.429, I2 = 94.9%), and snoring severity with 0-10 visual analog scale after surgery (mean difference: -4.966, 95% CI: -5.804 to -4.128, I2 = 96.4%). The success rate was 46% in mild/moderate OSA; however, 18% in severe OSA. There were no major complications occurred. CONCLUSIONS: The acceptable surgical outcomes, esp. in mild/moderate OSA, and rare complications are the major advantages of MISS MLS. The evidence of this study could aid the decision making in selecting suitable treatment programs for OSA patients.

Comprehensive analyses of fatty acid metabolism-related lncRNA for ovarian cancer patients.

Ovarian cancer (OC) is a disease with difficult early diagnosis and treatment and poor prognosis. OC data profiles were downloaded from The Cancer Genome Atlas. Eight key fatty acid metabolism-related long non-coding RNAs (lncRNAs) were finally screened for building a risk scoring model by univariate/ multifactor and least absolute shrinkage and selection operator (LASSO) Cox regression. To make this risk scoring model more applicable to clinical work, we established a nomogram containing the clinical characteristics of OC patients after confirming that the model has good reliability and validity and the ability to distinguish patient prognosis. To further explore how these key lncRNAs are involved in OC progression, we explored their relationship with LUAD immune signatures and tumor drug resistance. The structure shows that the risk scoring model established based on these 8 fatty acid metabolism-related lncRNAs has good reliability and validity and can better predict the prognosis of patients with different risks of OC, and LINC00861in these key RNAs may be a hub gene that affects the progression of OC and closely related to the sensitivity of current OC chemotherapy drugs. In addition, combined with immune signature analysis, we found that patients in the high-risk group are in a state of immunosuppression, and Tfh cells may play an important role in it. We innovatively established a prognostic prediction model with excellent reliability and validity from the perspective of OC fatty acid metabolism reprogramming and lncRNA regulation and found new molecular/cellular targets for future OC treatment.

The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

Development of Prognostic Biomarkers by TMB-Guided WSI Analysis: A Two-Step Approach.

The rapid development of computational pathology has brought new opportunities for prognosis prediction using histopathological images. However, the existing deep learning frameworks lack exploration of the relationship between images and other prognostic information, resulting in poor interpretability. Tumor mutation burden (TMB) is a promising biomarker for predicting the survival outcomes of cancer patients, but its measurement is costly. Its heterogeneity may be reflected in histopathological images. Here, we report a two-step framework for prognostic prediction using whole-slide images (WSIs). First, the framework adopts a deep residual network to encode the phenotype of WSIs and classifies patient-level TMB by the deep features after aggregation and dimensionality reduction. Then, the patients' prognosis is stratified by the TMB-related information obtained during the classification model development. Deep learning feature extraction and TMB classification model construction are performed on an in-house dataset of 295 Haematoxylin & Eosin stained WSIs of clear cell renal cell carcinoma (ccRCC). The development and evaluation of prognostic biomarkers are performed on The Cancer Genome Atlas-Kidney ccRCC (TCGA-KIRC) project with 304 WSIs. Our framework achieves good performance for TMB classification with an area under the receiver operating characteristic curve (AUC) of 0.813 on the validation set. Through survival analysis, our proposed prognostic biomarkers can achieve significant stratification of patients' overall survival (P 0.05) and outperform the original TMB signature in risk stratification of patients with advanced disease. The results indicate the feasibility of mining TMB-related information from WSI to achieve stepwise prognosis prediction.

CCNE1 is a predictive and immunotherapeutic indicator in various cancers including UCEC: a pan-cancer analysis.

BACKGROUND: CCNE1 plays an important oncogenic role in several tumors, especially high-stage serous ovarian cancer and endometrial cancer. Nevertheless, the fundamental function of CCNE1 has not been explored in multiple cancers. Therefore, bioinformatics analyses of pan-cancer datasets were carried out to explore how CCNE1 regulates tumorigenesis. METHODS: A variety of online tools and cancer databases, including GEPIA2, SangerBox, LinkedOmics and cBioPortal, were applied to investigate the expression of CCNE1 across cancers. The pan-cancer datasets were used to search for links between CCNE1 expression and prognosis, DNA methylation, m6A level, genetic alterations, CCNE1-related genes, and tumor immunity. We verified that CCNE1 has biological functions in UCEC cell lines using CCK-8, EdU, and Transwell assays. RESULTS: In patients with different tumor types, a high mRNA expression level of CCNE1 was related to a poor prognosis. Genes related to CCNE1 were connected to the cell cycle, metabolism, and DNA damage repair, according to GO and KEGG enrichment analyses. Genetic alterations of CCNE1, including duplications and deep mutations, have been observed in various cancers. Immune analysis revealed that CCNE1 had a strong correlation with TMB, MSI, neoantigen, and ICP in a variety of tumor types, and this correlation may have an impact on the sensitivity of various cancers to immunotherapy. CCK-8, EdU and Transwell assays suggested that CCNE1 knockdown can suppress UCEC cell proliferation, migration and invasion. CONCLUSION: Our study demonstrated that CCNE1 is upregulated in multiple cancers in the TCGA database and may be a promising predictive biomarker for the immunotherapy response in some types of cancers. Moreover, CCNE1 knockdown can suppress the proliferation, migration and invasion of UCEC cells.

Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women.

Introduction: Atrophy of the reproductive tract mucosa caused by the decrease of estrogen may increase the detection rate of ASC-US in cervical cytology of post-menopausal women. In addition, other pathogenic infections and inflammation can change the cellular morphology and increase the detection rate of ASC-US. However, further studies are needed to elucidate whether the high detection rate of ASC-US in post-menopausal women leads to the high referral rate of colposcopy. Methods: This retrospective study was conducted to document ASC-US in cervical cytology reports at the Department of Cytology at Gynecology and Obstetrics, Tianjin Medical University General Hospital between January 2006 and February 2021. We then analyzed 2,462 reports of women with ASC-US at the Cervical Lesions Department. A total of 499 patients with ASC-US and 151 cytology with NILM participants underwent vaginal microecology tests. Results: The average reporting rate of ASC-US in cytology was 5.7%. The detection rate of ASC-US in women aged > 50 years (7.0%) was significantly higher than that in women aged ≤50 years (5.0%) (P<0.05). The CIN2+ detection rate was significantly lower in the post- (12.6%) than in pre-menopausal (20.5%) patients with ASC-US (P <0.05). The prevalence of abnormal reporting rate of vaginal microecology was significantly lower in the pre-menopausal group (56.2%) than that in the post-menopausal group (82.9%) (P<0.05). The prevalence of bacterial vaginosis (BV) (19.60%) was relatively high in the pre-menopausal group, but the abundance of bacteria-inhibiting flora (40.79%) was mainly an abnormality in the post-menopausal group. The vaginal microecological abnormality rate of the women with HR-HPV (-) of ASC-US was 66.22%, which was significantly higher than that of the HR-HPV (-) and the NILM group (52.32%; P<0.05). Discussion: The detection rate of ASC-US in women aged > 50 years was higher than that ≤50 years, but the detection rate of CIN2+ was lower in the post-menopausal women with ASC-US. However, vaginal microecological abnormalities may increase the false-positive diagnosis rate of ASC-US. The vaginal microecological abnormalities of the menopausal women with ASC-US are mainly attributed to infectious diseases such as BV, and it mainly occurs in the post-menopausal women was bacteria-inhibiting flora. Therefore, to avoid the high referral rate for colposcopy, more attention should be paid to the detection of vaginal microecology.