Metal-Organic Framework-Induced Rh Monocoodination on Diphosphine Ligand Enables Catalytic Hydroformylation of Aliphatic Olefins at Room Temperature and Pressure.

Persistent challenges in hydroformylation of olefins include controlling regioselectivity, particularly for short aliphatic olefins and conducting reactions under ambient conditions.  We report here the synthesis of monophosphine-Rh complexes on a typical chelated diphosphine ligand mediated by a Zr-MOF through isolating a pair of phosphorus atoms. We demonstrate that single-crystal X-ray diffraction can elucidate the structural transformation of the Rh catalyst during olefin hydroformylation, providing valuable information on active site reconstruction during catalysis. The Rh-MOF catalyst demonstrates excellent catalytic and recyclable performance in the hydroformylation of short aliphatic olefins with linear to branched ratios of up to 99:1. Due to the framework's capacity to adsorb and concentrate gases, the catalytic reactions occur under room temperature and pressure, eliminating the need for the high temperature and pressures typically required in homogeneous systems. This study show that Zr-MOF can be a unique platform for synthesizing unusual catalytic species that cannot exist in solutions for meaningful chemical transformations and elucidate valuable structural information pertaining to metal-based catalysis.

[Landscape Pattern Vulnerability and Its Driving Forces in Different Geomorphological Divisions in the Middle Yellow River].

The ecological environment of the middle Yellow River is highly vulnerable. Conducting a scientific assessment of landscape pattern vulnerability holds great significance, as it serves as the basis for the rational construction of the ecological environment in this area. Based on five periods of land use data from the middle Yellow River from 1990 to 2018, the landscape pattern vulnerability index was employed to analyze the spatio-temporal evolution of the landscape pattern vulnerability. Furthermore, the influencing factors for landscape pattern vulnerability in different natural geomorphological divisions were explored using an optimal parameters-based geographical detector model. The results showed that:① From 1990 to 2018, cultivated land (which accounted for 36.96 % to 39.97 % of the area) remained the predominant landscape in the middle Yellow River. Among all landscape types, cultivated land and construction land exhibited the most significant changes. The area of cultivated land decreased by 10 185.00 km2, whereas the area of construction land increased by 7 678.46 km2. ② From 1990 to 2018, the landscape pattern was dominated by low and medium vulnerability and accounted for 70 %-80 % of the total area. The high and higher vulnerability areas were concentrated in the loess hilly and gully region, whereas the lower vulnerability area was concentrated in the valley plain and the earth-rock mountain regions. During this period, landscape pattern vulnerability underwent an incipient decrease, followed by a subsequent increase. From 1990 to 2000 and from 2000 to 2005, the changes in the level of landscape pattern vulnerability were dominated by a "reduction in the degree of vulnerability". However, from 2005 to 2010 and from 2010 to 2018, it was mainly an "increase in the degree of vulnerability". ③ Annual precipitation and NDVI were the main factors influencing the vulnerability of landscape patterns, whereas the influencing factors varied across different natural geomorphological divisions:the loess hilly and gully region and the earth-rock mountain region were dominated by natural factors, with annual precipitation and DEM being the dominant factors, respectively; the loess plateau tableland-gully region, valley plain region, and sandy land and desert region were dominated by human factors, with population density, degree of land use, and distance from roads being the dominant factors, respectively. The interaction results of any two influencing factors were manifested as two-factor enhancement or nonlinear enhancement. Risk detection revealed that high vulnerability areas of landscape patterns in different natural geomorphological divisions were distributed over distinct ranges of their corresponding dominant factors. Therefore, in the practices of ecological management in the middle Yellow River, appropriate management strategies should be implemented based on the vulnerability characteristics of different natural landforms, to further improve the ecological management level of the watershed.

A novel liver-function-indicators-based prognosis signature for patients with hepatocellular carcinoma treated with anti-programmed cell death-1 therapy.

BACKGROUND: The liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy. METHODS: Between July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan-Meier survival curves were utilized to access the predictive performance of LFIS. RESULTS: A total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child-Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature. CONCLUSION: The LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.

Patients with hepatocellular carcinoma extrahepatic metastases can benefit from hepatic arterial infusion chemotherapy combined with lenvatinib plus programmed Death-1 inhibitors.

BACKGROUND: Lenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. MATERIALS AND METHODS: This multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, the mOS (hazard ratio (HR)=0.384, P<0.001) and mPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05). CONCLUSION: HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.

Analysis of factors that promote the participation of patients with chronic diseases in shared decision making on medication: a cross-sectional survey in Hubei Province, China.

BACKGROUND: Shared decision making (SDM) improves the health status of patients with chronic diseases, especially in the condition of poly-medicated patients. This study aims to find the factors associated with participation of patients with chronic diseases in SDM on medication. METHODS: A total of 1,196 patients with chronic diseases were selected in Hubei Province of China using cluster sampling methods. The random forest method was applied to rank the importance of independent variables by Mean Decrease Gini and out-of- bag (OOB) curve. Multivariate logistic regression was used to explore the independent variables' effect direction and relative hazard. RESULTS: In this study, 5.18% of patients used patient-directed decision making (PDM, a decision-making model led by patients), 37.79% of patients used SDM (a collaborative decision-making model by patients and doctors), and 57.02% of patients used doctor-directed decision making (DDM, or paternalistic decision making, a decision-making model led by doctors). The random forest analysis demonstrated that the top 5 important factors were age, education, exercise, disease course, and medication knowledge. The OOB curve showed that the error rate reached minimum when top 5 variables in importance ranking composed an optimal variable combination. In multivariate logistic regression, we chose SDM as a reference group, and identified medication knowledge (OR = 2.737, 95%CI = 1.524 ~ 4.916) as the influencing factor between PDM and SDM. Meanwhile, the influencing factors between DDM and SDM were age (OR = 0.636, 95%CI = 0.439 ~ 0.921), education (OR = 1.536, 95%CI = 1.122 ~ 2.103), exercise (OR = 1.443, 95%CI = 1.109 ~ 1.877), disease course (OR = 0.750, 95%CI = 0.584 ~ 0.964), and medication knowledge (OR = 1.446, 95%CI = 1.120 ~ 1.867). CONCLUSION: Most Chinese patients with chronic diseases used DDM during their medication decision-making, and some patients used PDM and SDM. The participation in SDM should be taken seriously among elderly patients with lower education levels. The SDM promotion should focus on transformation of patients' traditional perception and enhance their medication knowledge.

Factors associated with the incidence and the expenditure of self-medication among middle-aged and older adults in China: A cross-sectional study.

Background: With the accelerated ageing of population and the growing prevalence of various chronic diseases in China, self-medication plays an increasingly important role in complementing the health care system due to its convenience and economy. Objective: This study aimed to investigate the incidence of self-medication and the amount of self-medication expenditure among middle-aged and older adults in China, and to explore factors associated with them. Methods: A total of 10,841 respondents aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) wave 4 which conducted in 2018 were included as the sample of this study. The two-part model was adopted to identify the association between the incidence of self-medication and the amount of self-medication expenditure and specific factors, respectively. Results: The incidence of self-medication among Chinese middle-aged and older adults was 62.30%, and the average total and out-of-pocket (OOP) pharmaceutical expenditure of self-medication of the self-medicated individuals were 290.50 and 264.38 Chinese yuan (CNY) respectively. Participants who took traditional Chinese medicine (TCM), self-reported fair, and poor health status, suffered from one and multiple chronic diseases had strongly higher incidence of self-medication. Older age and multiple chronic diseases were strongly associated with higher expenditure of self-medication. Those who took TCM had more self-medication expenditure, while those who drank alcohol had less. Conclusion: Our study demonstrated the great prevalence of self-medication among middle-aged and older adults in China and the large pharmaceutical expenditure that come with it, especially in the high-risk groups of self-medication identified in this paper. These findings enhanced our understanding of self-medication behaviors among Chinese middle-aged and older adults and may contribute to the formulation of targeted public health policy.

Is shared decision-making a determinant of polypharmacy in older patients with chronic disease? A cross-sectional study in Hubei Province, China.

BACKGROUND: Shared decision-making(SDM) is recognized as an important means of managing polypharmacy among older people with chronic diseases. However, no studies have quantitatively measured the effect of SDM on polypharmacy. The objective of this study was to compare the impact of SDM and other factors on polypharmacy in inpatients and community patients. Additionally, the study aimed to compare the impact of different decision types on polypharmacy in community patients. METHODS: This is a population-based multicenter retrospective study conducted in Hubei Province, China. A cluster sampling approach was used to recruit 536 chronic disease inpatients from March to April 2019, and 849 community patients were recruited from April to June 2021. Propensity score weighting was used to control the confounding variables and determine the net effect of SDM on polypharmacy. RESULTS: Among the 536 hospitalized patients, the prevalence of polypharmacy was 56.3%. A high level of SDM was significantly associated with a lower risk of polypharmacy. Patients with chronic illnesses aged 76 years and older and with an annual family income of 24,001-36,000 yuan were associated with a lower likelihood of polypharmacy (p < 0.05). Multimorbidity was often accompanied by the occurrence of multiple medication use. Among 849 community patients, the prevalence of polypharmacy was 21.8%. Among types of decision-making, informed and paternalistic decision-making showed a higher likelihood of polypharmacy compared with shared decision-making (P < 0.05). Male, older patients over 76 years of age, urban residents, annual household income of 12,001-24,000 yuan, and multimorbidity were associated with higher likelihood of polypharmacy (P < 0.05). Patients with an annual household income of 24,001-36,000 yuan, 36,001 yuan or more, and good medication compliance showed a lower likelihood of polypharmacy (P < 0.05). CONCLUSIONS: The prevalence of polypharmacy is high among China's older population with chronic disease who should be paid more atthention by the healthcare providers. Additionaly, encouraging the patients' attendance in SDM, reducing paternalistic and informed decision-making during prescribing, improving patient medication compliance, and increasing the promotion and guidance of rational medication use for patients are essential to reduce polypharmacy in Chinese chronic disease patients.

Peripheral Th and NK cells are associated with response to lenvatinib plus PD-1 inhibitor in unresectable hepatocellular carcinoma.

The value of peripheral blood lymphocyte subpopulations in predicting responses to lenvatinib combination with programmed death-1 (PD-1) inhibitors in unresectable hepatocellular carcinoma (HCC) was investigated. Fifteen patients received objective responses (OR) and sixteen patients had non-objective responses (NOR) were analyzed. The counts of peripheral blood lymphocyte subpopulations from patients were measured before treatment, second (at week 3), and third doses (at week 6) of the PD-1 inhibitor administration, and correlated with responses. Helper T (Th) cells and natural killers (NK) cells were more abundant in the OR group and found to be important predictors of OR in a stepwise multivariate logistic regression analysis. These cutoff values of Th and NK cells could help to distinguish OR from NOR cases accurately and provide clinical benefits.

Construction of Monophosphine-Metal Complexes in Privileged Diphosphine-Based Covalent Organic Frameworks for Catalytic Asymmetric Hydrogenation.

Privileged diphosphine ligands that chelate many transition metals to form stable chelation complexes are essential in a variety of catalytic processes. However, the exact identity of the catalytically active moieties remains ambiguous because the chelated metal catalysts may undergo rearrangement during catalysis to produce monophosphine-metal complexes, which are hard to isolate and evaluate the activities. By taking advantage of the isolation of two phosphorus atoms, we demonstrate here the successful construction of chiral monophosphine-Ir/Ru complexes of diphosphine ligands in covalent organic frameworks (COFs) for enantioselective hydrogenation. By condensation of the tetraaldehyde of enantiopure MeO-BIPHEP and linear aromatic diamines, we prepare two homochiral two-dimensional COFs with ABC stacking, in which the two P atoms of each diphosphine are separated and fixed far apart. Post-synthetic metalations of the COFs thus afford the single-site Ir/Ru-monophosphine catalysts, in contrast to the homogeneous chelated analogues, that demonstrated excellent catalytic and recyclable performance in the asymmetric hydrogenation of quinolines and ß-ketoesters, affording up to 99.9% enantiomeric excess. Owing to the fact that the porous catalyst is capable of adsorbing and concentrating hydrogen, the catalytic reactions are promoted under ambient/medium pressure, which are typically performed under high pressure for homogeneous catalysis. This work not only shows that monophosphine-metal complexes of diphosphines can be catalytically active centers for asymmetric hydrogenation reactions but also provides a new strategy to prepare new types of privileged phosphine-based heterogeneous catalysts.

Nomogram Based on Inflammatory Biomarkers to Predict the Recurrence of Hepatocellular Carcinoma-A Multicentre Experience.

Purpose: Our study aimed to identify inflammatory biomarkers and develop a prediction model to stratify high-risk patients for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) recurrence after curative resection. Patients and Methods: A total of 583 eligible HBV-HCC patients with curative hepatectomy from Guangdong Provincial People's Hospital (GDPH) and Sun Ya-sen University Cancer Centre (SYSUCC) were enrolled in our study. Cox proportional hazards regression was utilized to evaluate potential risk factors for disease-free survival (RFS). The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to assess the discrimination performance. Calibration plots and decision curve analyses (DCA) were used to evaluate the calibration of the nomogram and the net benefit, respectively. Results: Based on the systemic inflammation response index (SIRI), aspartate aminotransferase to neutrophil ratio index (ANRI), China Liver Cancer (CNLC) stage and microvascular invasion, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 2-, and 3-year RFS was 0.767, 0.726, and 0.708 in the training cohort and 0.761, 0.716, and 0.715 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability. Conclusion: The novel nomogram showed a higher prognostic power for the RFS of HCC patients with curative hepatectomy than the CNLC, AJCC 8th edition and BCLC staging systems and may help oncologists identify high-risk HCC patients.

Development and Validation of a Novel Mitochondrion and Ferroptosis-Related Long Non-Coding RNA Prognostic Signature in Hepatocellular Carcinoma.

Mitochondrion and ferroptosis are related to tumorigenesis and tumor progression of hepatocellular carcinoma (HCC). Therefore, this study focused on exploring the participation of lncRNAs in mitochondrial dysfunction and ferroptosis using public datasets from The Cancer Genome Atlas (TCGA) database. We identified the mitochondrion- and ferroptosis-related lncRNAs by Pearson's analysis and lasso-Cox regression. Moreover, real-time quantitative reverse transcription PCR (RT-qPCR) was utilized to further confirm the abnormal expression of these lncRNAs. Based on eight lncRNAs, the MF-related lncRNA prognostic signature (LPS) with outstanding stratification ability and prognostic prediction capability was constructed. In addition, functional enrichment analysis and immune cell infiltration analysis were performed to explore the possible functions of lncRNAs and their impact on the tumor microenvironment. The pathways related to G2M checkpoint and MYC were activated, and the infiltration ratio of regulatory T cells and M0 and M2 macrophages was higher in the high-risk group. In conclusion, these lncRNAs may affect mitochondria functions, ferroptosis, and immune cell infiltration in HCC through specific pathways, which may provide valuable insight into the progression and therapies of HCC.

Expression of ALG3 in Hepatocellular Carcinoma and Its Clinical Implication.

Background: Recent studies have shown that alpha-1,3-mannosyltransferase (ALG3) promoted tumorigenesis and progression in multiple cancer types. Our study planned to explore the clinical implication and potential function of ALG3 in hepatocellular carcinoma. Materials and Methods: Data from public databases were used to analyze the ALG3 expression and its impact on the clinical significance of patients with HCC. The ALG3 expression was confirmed by qRT-PCR and Western blot. Immunohistochemistry was used to confirm the ALG3 expression and explore its clinical implication in HCC. KEGG, GO, and GSEA enrichment analyses were utilized to explore the biological pathways related to ALG3 in HCC. TIMER2.0 was applied to assess the association between ALG3 and immune infiltration. CCK8, MTT, and transwell assays were used to investigate the role of ALG3 downregulation in HCC cell lines. Results: qRT-PCR, WB, and IHC proved ALG3 was highly overexpressed in HCC tissues. The Kaplan-Meier analysis verified the overexpression of ALG3 was related to poor overall survival (p < 0.001). Multivariate cox regression analysis showed that the high ALG3 expression was an independent risk prognostic factor. GSEA and TIMER2.0 predicted that ALG3 participates in cell differentiation and cycle and correlates with immune cell infiltration. Transwell assay results showed that ALG3 silencing also impaired the invasion ability of HCC cells. Conclusion: ALG3 was overexpressed and considered a potential indicator of survival in HCC, and our findings provided a novel therapeutic target for HCC.

Average Power Handling Capability of Corrugated Slow-Wave Transmission Lines.

In this article, the average power handling capability (APHC) of corrugated slow-wave transmission lines (SWTLs) is investigated. Firstly, the attenuation constants of conductor and dielectric are extracted by the multiline method. Secondly, the thermal resistance of corrugated SWTLs is analyzed based on the constant-angle model. To deal with the non-uniform corrugated structure of SWTLs, the concept of average heat-spreading width (AHSW) is introduced. Finally, the APHC of the corrugated SWTL is calculated using the attenuation constant and the thermal resistance. In addition, the APHC considering the temperature-dependent resistivity of metal conductor is also presented. For validation, the APHCs of SWTLs with different geometric parameters are evaluated. The results agree well with those obtained by the commercial software.

Microvascular Invasion in Hepatocellular Carcinoma: A Review of Its Definition, Clinical Significance, and Comprehensive Management.

Hepatocellular carcinoma (HCC) is one of the most common types of malignancies in the world, and most HCC patients undergoing liver resection relapse within five years. Microvascular invasion (MVI) is an independent factor for both the disease-free survival and overall survival of HCC patients. At present, the definition of MVI is still controversial, and a global consensus on how to evaluate MVI precisely is needed. Moreover, this review summarizes the current knowledge and clinical significance of MVI for HCC patients. In terms of management, antiviral therapy, wide surgical margins, and postoperative transcatheter arterial chemoembolization (TACE) could effectively reduce the incidence of MVI or improve the disease-free survival and overall survival of HCC patients with MVI. However, other perioperative management practices, such as anatomical resection, radiotherapy, targeted therapy and immune therapy, should be clarified in future investigations.

Does self-medication reduce medical expenditure among the middle-aged and elderly population? A four-wave longitudinal study in China.

Introduction: Self-medication has a high prevalence in the middle-aged and elderly population in China. Despite the published evidence demonstrating the economic benefits of self-medication, limited research has addressed the relationship between self-medication and individual medical expenditures, especially within the Chinese population. This study examined the effect of self-medication on individual medical expenditures in China and analyzed the heterogeneity between outpatient and inpatient cases. Methods: We conducted a panel data analysis using data from four waves of the China Health and Retirement Longitudinal Study (CHARLS). Two-part mixed-effect models were implemented to estimate the effect of self-medication on total outpatient and inpatient expenses and out-of-pocket (OOP) costs, where mixed-effects logit regression was used as the first part, and generalized linear mixed models with log link and gamma distribution was used as the second part. Results: We identified 72,041 responses representing 24,641 individuals, of which 13,185 responses incurred outpatient expenses and 9,003 responses incurred inpatient costs. Controlling for all covariates, we found that self-medication behaviors were significantly associated with a higher probability of outpatient service utilization (OR = 1.250, 95% CI = 0.179 to 0.269; P < 0.001), but displayed no significant association with outpatient expenses. Respondents who had taken self-medication were less likely to use inpatient services (OR = 0.865, 95% CI = -0.201 to -0.089; P < 0.001), and their inpatient expenses were significantly reduced by 9.4% (P < 0.001). Inpatient OOP costs were significantly reduced by 10.7% (P < 0.001), and outpatient OOP costs were significantly increased by 11.3% (P < 0.001) among respondents who had self-medicated. Conclusions: This study allowed us to identify the economic value of self-medication among the middle-aged and elderly population in China. Future work should guide the middle-aged and elderly to take responsible self-medication to reduce their economic burden.

Predictors of Polypharmacy Among Elderly Patients in China: The Role of Decision Involvement, Depression, and Taking Chinese Medicine Behavior.

Introduction: The prevalence of polypharmacy is gradually increasing in geriatrics, which may contribute to adverse effects, such as potential drug-drug and drug-disease interactions. These side effects remain an important challenge in patient safety, which has a significant impact on mortality and incidence rate. Aims: Therefore, this study aims to understand the epidemiology of polypharmacy and identify factors that have an impact on the management of potentially inappropriate prescribing. Methods: This study is a cross-sectional study, analyzing the prescription data from 720 hospitalized patients aged 50+ with a random cluster sampling method. We used inverse probability treatment weighting (IPTW) method to group and match polypharmacy and non-polypharmacy patients, and logistic regression was conducted to explore the factors associated with polypharmacy. Results: The prevalence of polypharmacy accounted for 50.14% among the old patients in this study. Female patients (67.34%) have more polypharmacy than male patients, and key predictors associated with polypharmacy in the logistic regression model included the following: domicile (AOR = 0.63, 95% CI 0.42-0.95), annual income (AOR = 0.38, 95% CI 0.20-0.70), the number of chronic diseases (AOR = 3.68, 95% CI 2.69-5.06), taking Chinese medicine (AOR = 1.70, 95% CI 1.22-2.36), decision involvement (AOR = 1.49 95% CI 1.10-2.03), and depression (AOR = 1.42, 95% CI 1.03-1.96). Conclusion: Polypharmacy is common among the participants with chronic diseases in Hubei province, China. The study emphasizes that gerontology practitioners should be prudent in applying clinical guidelines to provide personalized, comprehensive assessment of decision making of prescriptions, especially in socioeconomically deprived areas.

Development of a KRAS-Associated Metabolic Risk Model for Prognostic Prediction in Pancreatic Cancer.

BACKGROUND: KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there was no comprehensive analysis to explore KRAS-associated metabolic signature or risk model for pancreatic cancer (PC). METHODS: In the current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then, we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association between the risk model and the metabolic characteristics as well as gemcitabine-associated chemoresistance in PC. RESULTS: 6 KRAS-associated metabolic genes (i.e., CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then, the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis-associated genes (PKM, GLUT1, HK2, and LDHA) and gemcitabine-associated chemoresistance genes (i.e., CDA and RMM2) was significantly upregulated in high-risk PC patients evaluated by the risk model. CONCLUSIONS: We constructed a risk model based on 6 KRAS-associated metabolic genes, which predicted patients' survival with high accuracy and reflected tumor metabolic characteristics and gemcitabine-associated chemoresistance in PC.

Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16.

Background: Tumor-derived exosomes (EXOs), commonly differentially expressed in circular RNAs, have been shown to be crucial determinants of tumor progression and may regulate the development and metastasis of hepatic carcinoma (HCC). Methods: Possibly differentially expressed circRNAs in patients with HCC were screened out from the Gene Expression Omnibus (GEO). EXOs were isolated from the culture medium of HCC cells and plasma of patients with HCC, followed by characterization by transmission electron microscope, NanHCCight, and western blotting. Additionally, RNA immunoprecipitation and luciferase reporter gene assays were carried out to explore the molecular mechanism of hsa_circRNA_103809 (circ-0072088) in HCC cells. Results: The screening results showed that circ-0072088 was highly expressed in patients with HCC, and its increase indicated unfavorable prognosis of patients according to quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, circ-0072088 was mainly secreted by HCC cells via EXOs in plasma of such patients, and its high level in plasma EXOs was closely associated with tumor node metastasis (TNM) staging and tumor size. Moreover, HCC-secreted EXOs mediated the degradation of miR-375 via circ-0072088 and upregulated MMP-16, thus suppressing the metastasis of HCC. Conclusion: Upregulated in patients with HCC, circ-0072088 may be an index for diagnosis and prognosis of HCC. In addition, HCC-derived EXOs coated with circ-0072088 might be a treatment for HCC, with the ability to inhibit the metastasis of HCC cells.

SLC39A10 Upregulation Predicts Poor Prognosis, Promotes Proliferation and Migration, and Correlates with Immune Infiltration in Hepatocellular Carcinoma.

BACKGROUND: Recent evidence has shown that Solute Carrier Family 39 Member 10 (SLC39A10) promoted tumor progression in several cancer types. The study intended to explore the expression and function of SLC39A10 in hepatocellular carcinoma (HCC). METHODS: Multiple bioinformatics analyses were used to evaluate SLC39A10 expression and potential role in HCC. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to confirm SLC39A10 expression. Intro studies were performed to assess the effects of SLC39A10 on HCC cells proliferation and migration. Furthermore, flow cytometry was conducted to identify its specific function in apoptosis of HCC. RESULTS: SLC39A10 was significantly over-expressed in HCC samples from both bioinformatic databases and our cohort. Survival analyses suggested patients with high expression of SLC39A10 had poor overall survival and disease-free survival (P-value <0.01). Further, the expression of SLC39A10 was positively correlated with tumor-infiltrating lymphocytes and some immune checkpoints like CTLA4, TIM3 and TGFB1. In HCC cell lines, SLC39A10 knockdown inhibited cells proliferation and migration, but promoted apoptosis. CONCLUSION: An increased SLC39A10 expression was found and served as an unfavorable indicator of survival in HCC. Further studies suggested SLC39A10 promotes tumor aggressiveness and may provide a novel target for HCC therapy.

A Novel Prognostic Nomogram for Gallbladder Cancer after Surgical Resection: A Single-Center Experience.

BACKGROUND: Gallbladder cancer (GBC), which accounts for more than 80% of biliary tract malignancies, has a poor prognosis with an overall 5-year survival less than 10%. The study aimed to identify risk factors and develop a predictive model for GBC following surgical resection. METHODS: 98 GBC patients who underwent surgical resection from Guangdong Provincial People's Hospital were enrolled in the study. Cox-regression analysis was performed to identify significant prognostic factors. A nomogram was constructed and Harrell's concordance index, calibration plot, and decision cure analysis were used to evaluate the discrimination and calibration of the nomogram. RESULTS: Liver resection, tumor size, perineural invasion, surgical margin, and liver invasion were identified as independent risk factors for overall survival (OS) in GBC patients who underwent surgical resection. Based on the selected risk factors, a novel nomogram was constructed. The C-index of the nomogram was 0.777, which was higher than the American Joint Committee on Cancer (AJCC) staging system (0.724) and Nevin staging system (0.659). Decision cure analysis revealed that the nomogram had a better net benefit and the calibration curves for the 1-, 3-, and 5-year survival probabilities were also well matched with the actual survival rates. Lastly, high-risk GBC were stratified based on the scores of the nomogram and we found high-risk GBC were associated with both worse OS and disease-free survival (DFS). CONCLUSION: We developed a nomogram showing a better predictive capacity for patients' survival of resected GBC than the AJCC staging systems. The established model may help to stratify high-risk GBC and facilitate decision-making in the clinic.