The Clinical Association Between the Inflammation-Nutritional Condition and Prognosis of Locally Advanced Intrahepatic Cholangiocarcinoma After R0 Resection: Evidence from Competing Risk and Propensity Matching Analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection. Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes. Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels, and postoperative adjuvant therapy. Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.

Comparison of perioperative and oncologic outcomes after open, laparoscopic, and robotic distal pancreatectomy: a single-center retrospective study.

As minimally invasive surgery gains grounds, surgeons are switching more towards laparoscopic distal pancreatectomy (LDP) and robotic distal pancreatectomy (RDP) as opposed to open distal pancreatectomy (ODP). Through this study, we aimed at exploring the differences in perioperative and oncologic outcomes among the three surgical methods. We retrospectively collected data from 303 patients who underwent distal pancreatectomy (DP) at a single high-volume institution between June 2015 and December 2021. We equally compared the perioperative and oncologic outcomes in patients who underwent ODP, LDP, and RDP by analyzing clinicopathologic and survival data. We consecutively included 303 cases in the study: open = 147 (48.5%), laparoscopic = 50 (16.5%), and robotic = 106 (35.0%). The median tumor size was significantly larger in the ODP group (P < 0.001) compared to the others. Cases in the RDP group experienced a longer duration of surgery (P < 0.001), smaller amount of blood loss (P < 0.001), smaller amount of blood transfusion (P = 0.042), and a shorter duration of hospital stay (p = 0.040) compared to cases in the ODP group. There was no significant difference observed when comparing other postoperative outcomes across the groups. Overall survival (OS) and progression-free survival (PFS) were similar across the significant differences among the three groups. The short-term postoperative and oncologic outcomes observed in the RDP and LDP groups were not inferior to those in the ODP group. The RDP has some perioperative advantages over the ODP. Therefore, RDP and LDP can safely and feasibly be performed in selected pancreatic tumors by experienced pancreatic surgeons.

Adjuvant chemotherapy combined with immunotherapy in patients with cholangiocarcinoma after radical resection.

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.

IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer.

OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.

Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis.

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Modified staging system of positive lymph nodes based nomogram in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) presents the similar trend and prevalence of lymph node metastasis to other biliary tract cancer. There is still a necessity and possibility for the current classification of lymph node in the 8th TNM of iCCA, which is the same as the criteria of hepatoma carcinoma (HCC), to further improve the prognostic capacity. We aim to explore the optimal positive lymph nodes cutoff value that could predict the survival outcomes of patients with iCCA and further establish a prognostic nomogram. METHOD: Clinical characteristics were retrospectively collected in 292 patients with iCCA from Sun Yat-sen University Cancer Center (SYSUCC) for preliminary analysis. A retrospective analysis of 107 patients with iCCA in the First Hospital of Dalian Medical University (FHDMU) was performed for verification. R software was used to determine the optimal cutoff value of positive lymph nodes (PLN) and further establish the nomogram with the Cox regression model in the primary cohort. RESULTS: In those patients who were graded into the N1 stage in 8th TNM staging system, the patients with PLN between 1 and 3 showed significantly better overall survival than those patients with more than 4 PLN (P < 0.0001). Moreover, there was a significant correlation between the new PLN classification and adverse clinical characteristic including Micro Invasion (P = 0.001), Lymph Vessel Invasion (P = 0.040), Satellite Sites (P < 0.001), and Tumor Size (P = 0.005). The PLN and ELN were both independent prognostic factors for survival outcomes in the multivariate analysis, and further showed large contribution to the nomogram. The nomogram achieved a satisfied C-index of 0.813 for overall survival (OS), 0.869 for progression-free survival (PFS) in the primary cohort, and 0.787 for OS, 0.762 for PFS in the validation cohort. CONCLUSION: The modified classification of PLN in iCCA could accurately stratify the N1 stage patients in 8th TNM staging system into two groups with significantly different overall survival. The development of this nomogram can offer new evidence to precisely post-operative management of iCCA patients.

Establishment and validation of a prognostic signature for pancreatic ductal adenocarcinoma based on lactate metabolism-related genes.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancy with poor prognosis. To improve patient outcomes, it is necessary to gain a better understanding of the oncogenesis and progression of this disease. Metabolic reprogramming, particularly the regulation of lactate metabolism, is known to have a significant impact on tumor microenvironment and could provide valuable insights for the management of PDAC patients. In this study, we aimed to investigate the prognostic potential of lactate metabolism-related genes (LMRGs). Methods: Transcriptomic data of patients with PDAC along with the clinical outcomes were retrieved from The Cancer Genome Atlas database, and the expression data in normal pancreas from Genotype-Tissue Expression dataset were adopted as the normal control. By using Cox and LASSO regression models, we identified key genes that are differentially expressed in cancerous tissues and related to prognosis. To determine the prognostic value of LMRGs in PDAC, we evaluated their clinical significance and model performance using both the area under the receiver operator characteristic curve (AUC) and calibration curves. In addition, we evaluated the drug sensitivity prediction and immune infiltration by using oncoPredict algorithm, single sample gene set enrichment analysis and Tumor Immune Estimation Resource. Results: A total of 123 LMRGs were identified through differential gene screening analysis, among which 7 LMRGs were identified to comprise a LMRGs signature that independently predict overall survival of these PDAC patient. The AUC values for the LMRGs signature were 0.786, 0.820, 0.837, and 0.816 for predicting 1-, 2-, 3- and 5-year overall survival respectively. Furthermore, this prognostic signature was used to stratify patients into high-risk and low-risk groups, with the former having worse clinical outcomes. This observation was further validated through analysis of the International Cancer Genome Consortium database. In addition, lower sensitivity to gemcitabine and infiltration of immune effector cells were observed in the cancer tissue of patients in the high-risk group. Conclusion: In conclusion, our data suggests that a genomic signature comprised of these LMRGs may be a novel predictor of overall clinical outcomes and present therapeutic potential for PDAC patients.

Interaction between Pelvic Bone Mineral Density and Sex Steroid Hormone on the Risk of Urinary Incontinence from National Health and Nutrition Examination Survey 2013-2014.

INTRODUCTION: The correlation between sex hormone levels and pelvic bone mineral density in people with urinary incontinence (UI) has not been evaluated. This study explored the association between sex hormones, pelvic bone mineral density, and UI, and analyzed the association between pelvic bone mineral density-combined sex hormones and UI in women. METHOD: The data of the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were used in this cross-sectional study. Women aged 20 years and older with complete sex steroid hormone and pelvic bone mineral density data were included. Outcomes were stress UI (SUI), urgency UI (UUI), and mixed UI (MUI). Sex steroid hormone included testosterone, estradiol, and sex hormone binding globulin (SHBG). Multivariate logistic regression analyses with the odds ratios (ORs) and 95% confidence intervals (CIs) were used. RESULTS: Of 2,442 women, 579 had SUI, 202 had UUI, and 344 had MUI. The estimated multiplicative interactions were significantly between testosterone and pelvic bone mineral density, between SHBG and pelvic bone mineral density on UI (p = 0.002, p = 0.003), MUI (p = 0.036, p < 0.001), and SUI (p = 0.008, p = 0.044), respectively. High pelvic bone mineral density was associated with UI (p = 0.022) and MUI (p = 0.028) in the age <45-year-old subgroup. Multiplicative interactions were between testosterone and pelvic bone mineral density on all types of UI in the age <45-year-old subgroup, on SUI in women who did not have vaginal deliveries, and on UI in women who had more than one-time vaginal delivery. CONCLUSION: Our study found negatively multiplicative interactions between testosterone, SHBG, and pelvic bone mineral density on UI, MUI, and SUI. Similar results were found in women aged <45 years old and in women who had more than one-time vaginal delivery. Clinicians may consider testosterone or SHBG supplementation and pelvic density enhancement in women with SUI, MUI, and low endogenous testosterone levels.

Alternatively-spliced lncRNA-PNUTS promotes HCC cell EMT via regulating ZEB1 expression.

BACKGROUND: Long non-coding RNAs have been implicated in various cancers as they regulate critical cellular processes such as proliferation, migration, invasion, and apoptosis in tumorous tissues. lncRNA-PNUTS is newly reported as an alternatively-spliced lncRNA from PNUTS pre-mRNA that promotes oncogenesis in breast cancer. However, whether LncRNA-PNUTS plays a role in other forms of cancers, such as liver cancer, remains unknown. METHOD: In the current study, we investigated the potential role of lncRNA-PNUTS in hepatocellular carcinoma (HCC). The levels of lncRNA-PNUTS in tumorous tissues obtained from HCC patients were measured. The potential impacts of lncPNUTS on metastasis and invasion were investigated through gain- or loss- of function experiments in cell models of liver cancers, as well as other cellular assays such as trans-well assays and wound-healing assays. RESULTS: Here, we report that lncPNUTS was upregulated in human HCC tissues. Loss- and gain-of-function experiments indicated lncPNUTS promoted metastasis and invasion. In addition, ZEB1, which is involved in the activation of epithelial-mesenchymal-transition (EMT), was identified as a downstream target of lncPNUTS. CONCLUSION: Our findings indicated lncPNUTS promotes HCC cancer cell metastasis and invasion via targeting ZEB1 to activate the EMT pathway, suggesting that lncPNUTS is a potential prognostic marker and therapeutic target for HCC patients.

Efficacy and safety of adjuvant chemotherapy in T1N0M0 intrahepatic cholangiocarcinoma after radical resection.

OBJECTIVE: Adjuvant chemotherapy is necessary for radical resection of intrahepatic cholangiocarcinoma (ICC) with a high risk of recurrence (T2-4, N1). However, its use in the treatment of early-stage ICC remains controversial. This study aimed to investigate the role of adjuvant chemotherapy after radical resection in patients with early-stage ICC (T1N0M0). DATA AND METHODS: The data of 148 patients with pathologically diagnosed ICC (T1N0M0) who underwent radical resection from January 2012 to January 2018 at the Sun Yat-sen University Cancer Center were retrospectively analyzed. Using consistent baseline data, Kaplan-Meier survival curves were constructed to compare relapse-free survival (RFS) and overall survival (OS) between patients who received postoperative adjuvant chemotherapy (AC group) and those who received only surgical treatment (non-AC group). Univariate and multivariate Cox regression analyses were used to screen for independent prognostic factors affecting survival. The RFS and OS of patients were analyzed after the administration of three adjuvant chemotherapy regimens (gemcitabine + capecitabine [GX], gemcitabine + cisplatin [GP], and capecitabine monotherapy [X]). Finally, the safety of adjuvant chemotherapy was evaluated based on the incidence of grade 1-4 adverse events. RESULTS: The median RFS was 18 months in the non-AC group and 25 months in the AC group. The median OS was 34 months in the non-AC group; however, it was not reached in the AC group. The OS of the AC group was significantly higher than that of the non-AC group (P = 0.005). Multivariate Cox analysis demonstrated that nerve invasion (P = 0.001), preoperative elevation of cancer antigen 19-9 (CA 19-9) levels (P = 0.009), and postoperative adjuvant chemotherapy (P = 0.009) were independent prognostic factors for early-stage ICC after radical resection. The OS rates of the GX, GP, X, and non-AC groups were significantly different (P = 0.023) and were higher in the GX group than in the non-AC group (P = 0.0052). Among patients with elevated preoperative CA 19-9 levels, the OS rate was higher in the AC group than in the non-AC group (P = 0.022). In terms of safety, the incidence of grade 3 or 4 adverse reactions was < 18.2% in the GX, GP, and X groups, without the occurrence of death owing to such reactions. CONCLUSION: Adjuvant chemotherapy can prolong OS among patients with early-stage ICC who have undergone radical resection. Preoperative elevation of CA 19-9 levels and nerve invasion are independent prognostic factors for poor survival outcomes for early-stage ICC after radical resection. All chemotherapy regimens used in the study are safe.

Development and verification of a nomogram for predicting the prognosis of resectable gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. PATIENTS AND METHODS: Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. RESULTS: Multivariate analysis showed that the surgical procedure (P < 0.001), period of chemotherapy (P < 0.001), T stage (P = 0.006), N stage (P = 0.040), systemic immune-inflammatory index (SII) (P < 0.001), and fibrinogen level (P = 0.026) were independent factors affecting OS. The nomogram constructed on the aforementioned factors for predicting the 1- and 3-year OS achieved a Harrell's concordance index (C-index) of 0.756 and 0.763 for the training and verification cohorts, respectively. Compared with the 8th American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM) staging system, the nomogram had higher C-index values and areas under the curve (AUCs) and slightly higher net clinical benefit. CONCLUSION: Compared to the 8th AJCC staging system, the newly developed nomogram showed superior performance in predicting the survival of GC patients with GOO after gastrectomy.

A Positive Feedback Loop between Inactive VHL-Triggered Histone Lactylation and PDGFRß Signaling Drives Clear Cell Renal Cell Carcinoma Progression.

Inactive von Hippel-Lindau (VHL) is linked to metabolic reprogramming and plays pivotal roles in the pathogenesis of clear cell renal cell carcinoma (ccRCC). Here, we identify a previously unknown oncogenic role for inactive VHL in actively triggering histone lactylation to promote ccRCC progression. In patients with ccRCC, inactive VHL positively correlates with the presence of histone lactylation, and high levels of histone lactylation indicates poor patient prognosis. Inactive VHL-triggered histone lactylation contributes to ccRCC progression by activating the transcription of platelet-derived growth factor receptor ß (PDGFRß). In turn, PDGFRß signaling is shown to stimulate histone lactylation, thereby forming an oncogenic positive feedback loop in ccRCC. Target correction of aberrant histone lactylation represses the growth and metastasis of ccRCC in vivo. More importantly, the combined inhibition of histone lactylation and PDGFRß significantly reinforces the therapeutic efficacy. This work underscores the importance of histone lactylation in facilitating ccRCC progression and suggests targeting the positive feedback loop between histone lactylation and PDGFRß signaling might provide a promising therapeutic strategy for ccRCC patients.

Progression Patterns and Post-Progression Survival in Recurred Intrahepatic Cholangiocarcinoma Patients: A Novel Prognostic Nomogram Based on Multicenter Cohorts.

Background: The post-progression survival (PPS) of recurred intrahepatic cholangiocarcinoma (iCCA) patients relates to the characteristics of tumor progression. Moreover, the prediction model of PPS in those patients has not been well established. This study aimed at developing a novel nomogram for predicting PPS in recurred iCCA patients. Method: Clinical characteristics were retrospectively collected in 396 patients diagnosed with iCCA from cohorts of Sun Yat-sen University Cancer Center (SYSUCC) and the First Hospital of Dalian Medical University (FHDMU). The PPS in patients with different progression patterns was investigated. The nomogram of PPS was established with the Cox regression model in the primary cohort. Then the nomogram was verified in the external validation cohort. Results: Liver progression was the commonest pattern (42.08%) in recurred iCCA patients, while patients with local LN progression had significantly better PPS than those with other patterns. The independent prognostic factors comprised elevated CEA levels, tumor differentiation, N stage 8th, adjuvant therapy, Local LN metastasis, Liver Metastasis only, and Multiple Metastasis. The nomogram constructed on these factors achieved satisfied C-indexes of 0.794 (95% CI 0.769-0.828) and 0.827 (0.779-0.876) for the training and validation cohorts, respectively. These values were significantly higher than those of the 8th TNM stage system (all p < 0.001). The recurred iCCA patients could be precisely classified into high- and low-risk groups according to the cutoff point of this nomogram (p < 0.01). Conclusion: The investigation of progression patterns and the development of this nomogram can offer new evidence to precisely postoperative and post-progression management of iCCA patients.

Acidic Electrolyzed Water Inhibits the Viability of Gardnerella spp. via Oxidative Stress Response.

The vaginal microbiota, dominated by Lactobacilli, plays an important role in maintaining women's health. Disturbance of the vaginal microbiota allows infection by various pathogens such as Gardnerella spp. (GS) and related anaerobic bacteria resulting in bacterial vaginosis (BV). At present, the treatment options for BV are extremely limited. Treatment of antibacterial drugs and vaginal acidification are the two primary therapeutic methods. Acid electrolyzed water (AEW) is known to inactivate microorganisms and is considered a medical application in recent years. Studies have found that Lactobacillus acidophilus (LA) probiotics helps to inhibit GS-induced BV. Our study took GS and LA as the research object, which aims to explore AEW as a potential alternative therapy for BV and its underlying mechanisms. We first obtained the pH of AEW (3.71-4.22) close to normal vaginal pH (3.8-4.5) to maintain normal vaginal acidification conditions. Plate counting experiments showed that AEW (pH: 4.07, ORP: 890.67, ACC: 20 ppm) (20 ppm) could better inhibit the viability of GS but had a more negligible effect on LA. Then, we preliminarily explored the possible mechanism of AEW anti-GS using cell biology experiments and transmission electron microscopy. Results showed that the membrane permeability was significantly increased and the integrity of cell membrane was destroyed by AEW in GS than those in LA. AEW also caused protein leakage and cell lysis in GS without affecting LA. Meanwhile, AEW induced a number of reactive oxygen species (ROS) production in GS, with no obvious LA changes. Finally, we found that 20 ppm AEW exhibited excellent antibacterial effect on the vaginal secretions of women diagnosed with BV by Amsel criteria and sialic acid plum method. Taken together, our findings manifest that 20 ppm AEW has an excellent antibacterial effect in GS with less effect on LA, which might be expected to become a potential therapy for BV.

Evaluation of Preoperative Inflammation-Based Prognostic Scores in Patients With Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study.

BACKGROUND: Accumulating evidence has indicated the vital role of inflammation-based score (IBS) in predicting the prognostic outcome of cancer patients. Otherwise, their value in intrahepatic cholangiocarcinoma (iCCA) remains indistinct. The present study aimed to evaluate whether IBSs were related to survival outcomes in iCCA patients. METHOD: Clinical characteristics were retrospectively collected in 399 patients diagnosed with iCCA from cohorts of Sun Yat-sen University Cancer Center (SYSUCC) and the First Hospital of Dalian Medical University (FHDMU). The survival curves were constructed with the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were conducted to determine the prognostic factors of overall survival (OS) and progression-free survival (PFS). The concordance index and the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) were used to compare the predictive value of inflammation-based scores in terms of survival outcomes. RESULTS: The significant survival differences in OS and DFS were observed when patients were stratified by the modified Glasgow Prognostic Score (mGPS) (p<0.001). Multivariate analysis demonstrated that higher mGPS score was independently associated with poor OS and DFS (p<0.001). The predictive accuracy of the mGPS was superior to other IBSs (all p<0.001) in survival prediction in iCCA patients. The findings were further supported by the external validation cohort. CONCLUSION: The mGPS is a sensitive, efficient, simple and widely applicable preoperative prognostic factor for iCCA patients. Thus, more effective therapy and frequent surveillance should be conducted after surgical resection in iCCA patients with higher mGPS scores.

An Inflammation-Index Signature Predicts Prognosis of Patients with Intrahepatic Cholangiocarcinoma After Curative Resection.

BACKGROUND: The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) after resection is at great variance. We aimed to establish a novel prognostic nomogram in facilitating the risk stratification for these patients. METHODS: A total of 82 high-dimensional radiological and pathological data were analyzed by LASSO-penalized Cox regression analyses and the panels with the best predictive performance were selected. Specific nomograms were established based on the selected panels and were validated in both primary (n=292) and validation cohorts (n=107). The area under the receiver operating characteristic curve (AUC) and the concordance index (C-index) were used to compare the predictive ability of nomograms and other staging systems. RESULTS: The modified Glasgow Prognostic Score (mGPS) was identified as the prognostic factor for both overall survival (OS) and progression-free survival (PFS). The nomograms built on the prognostic factors showed powerful efficacy in survival prediction, with C-indexes of 0.800 (95% CI 0.767-0.833) and 0.752 (95% CI 0.718-0.786) for OS and PFS in the primary cohort, 0.659 (95% CI 0.586-0.732) and 0.638 (95% CI 0.571-0.705) for OS and PFS in the validation cohort, respectively. Compared with tumor-node-metastasis stage, Barcelona Clinic Liver Cancer staging score, Cancer of the Liver Italian Program score, and Okuda staging system, the nomograms had significantly higher values of AUC and C-indexes in survival prediction in the primary and validation cohorts. CONCLUSION: Compared with currently used staging systems, the nomograms showed significantly higher efficacy in predicting survival of ICC patients after resection. The nomograms provide new versions of personalized management for these patients.

Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment. METHODS: Between March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups. RESULTS: ICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort. CONCLUSIONS: HAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.

A Smart Robotic Walker With Intelligent Close-Proximity Interaction Capabilities for Elderly Mobility Safety.

The elderly population has rapidly increased in past years, bringing huge demands for elderly serving devices, especially for those with mobility impairment. Present assistant walkers designed for elderly users are primitive with limited user interactivity and intelligence. We propose a novel smart robotic walker that targets a convenient-to-use indoor walking aid for the elderly. The walker supports multiple modes of interactions through voice, gait or haptic touch, and allows intelligent control via learning-based methods to achieve mobility safety. Our design enables a flexible, initiative and reliable walker due to the following: (1) we take a hybrid approach by combining the conventional mobile robotic platform with the existing rollator design, to achieve a novel robotic system that fulfills expected functionalities; (2) our walker tracks users in front by detecting lower limb gait, while providing close-proximity walking safety support; (3) our walker can detect human intentions and predict emergency events, e.g., falling, by monitoring force pressure on a specially designed soft-robotic interface on the handle; (4) our walker performs reinforcement learning-based sound source localization to locate and navigate to the user based on his/her voice signals. Experiment results demonstrate the sturdy mechanical structure, the reliability of multiple novel interactions, and the efficiency of the intelligent control algorithms implemented. The demonstration video is available at: https://sites.google.com/view/smart-walker-hku.

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR-221 and the MAPK signaling pathway.

Homeodomain-containing gene 10 (HOXC10) is associated with the progression of a variety of different types of human cancer; however, the role of HOXC10 in liver cancer is not completely understood. The present study aimed to investigate the mechanisms underlying the effects of HOXC10 on liver cancer tumorigenesis. Quantitative PCR and western blotting were used to detect the expression patterns of HOXC10 in cancer and adjacent healthy tissues. EdU, Cell Counting Kit-8 and colony formation assays were used to determine the functions of HOXC10 in liver cancer cell lines. ENCORI, TargetScan and miRTarBase were used to identify microRNAs that target HOXC10. The verification of the interaction between HOXC10 and microRNA-221 was determined by a luciferase assay. Compared with adjacent non-cancerous tissues, the expression of HOXC10 was markedly decreased in liver cancer tissues. A HOXC10 small interfering (si)RNA significantly attenuated HOXC10 expression at the mRNA and protein levels, and enhanced cell proliferation compared with the siRNA-negative control group. In addition, the luciferase reporter assay indicated that microRNA-221 directly bound to the 3'-untranslated region of HOXC10, and interfered with the inhibitory effect of HOXC10 on proliferation. In addition, HOXC10 knockdown elevated the expression levels of mitogen-activated protein kinase signaling pathway markers compared with the siRNA-negative control group. Therefore, the results of the present study may aid with the development of novel therapeutic regimens and diagnostic markers of liver cancer.

Estrogen Receptor alpha depletion affects the biomechanical properties and cytoskeleton rearrangements in breast cancer cells.

Estrogen Receptor alpha (ERα) affects the morphology of tumors, which is closely related to the biomechanical properties and the cytoskeletal proteins. In recent years, researchers have found that biomechanical properties and cytoskeletal proteins are closely related to the occurrence and development of tumors and that biomechanical properties can be used as markers for tumor development and drug resistance. The relationship between ERα expression status and biomechanical properties, cytoskeletal proteins is not known. In this study, we found that tamoxifen-resistant breast cancer cells (MCF-7/TamR) altered cell morphology and lacked of ERα expression during the process of the Tamoxifen resistance induction. To determine whether this change was influenced by ERα expression, we transiently constructed another ERα depleted model with ERα siRNA (MCF-7/ERα siRNA) and used atomic force microscope (AFM) to detect morphological and biophysical changes. The results indicated that the roughness and Young's modulus of ERα expression depleted cells were significantly increased, accompanied by rearrangement of the cytoskeletal proteins (F-actin, FLNA, α-tubulin) and the cytoskeletal regulatory protein Rho (Rac1, CDC42) decreased. Our results have demonstrated that ERα depletion affects the biomechanical properties of breast cancer cells, which are related to cytoskeletal protein rearrangement and Rho protein decreased.