Deciphering the pancreatic cancer microbiome in Mainland China: Impact of Exiguobacterium/Bacillus ratio on tumor progression and prognostic significance.

The existing body of research underscores the critical impact of intratumoral microbiomes on the progression of pancreatic ductal adenocarcinoma (PDAC), particularly in reshaping the tumor microenvironment and influencing gemcitabine resistance. However, peritumoral tissues' microbiome, distinct from PDAC tumors, remain understudied, and Western-centric analyses overlooking potential variations in dietary-influenced microbiomes. Our study addresses this gap by 16 S rRNA sequencing of PDAC tumors and matched peritumoral tissues from Chinese Mainland patients. Our research has uncovered that the microbiome composition within tumors and paired peritumoral tissues exhibits a high degree of similarity, albeit with certain discrepancies. Notably, Exiguobacterium is found to be more abundant within the tumor tissues. Further investigations have revealed that a lower Exiguobacterium/Bacillus ratio in both the tumor and peritumoral tissues of PDAC patients is indicative of a more favorable prognosis. Further exploration utilizing an orthotopic tumor model demonstrates that the probiotic Bacillus Coagulans impedes PDAC progression, accompanied by an increased infiltration of inflammatory neutrophils in tumors. Additionally, in the subgroup with a low Exiguobacterium/Bacillus ratio, whole-exome sequencing reveals elevated missense mutations in ABL2 and MSH2. The elevated expression of ABL2 and MSH2 has been correlated with poorer prognostic outcomes in PDAC patients. Together, these insights shed light on risk factors influencing PDAC progression and unveil potential therapeutic targets, alongside probiotic intervention strategies.

Latent Profile Analysis of Suicidal Ideation in Chinese Individuals with Bipolar Disorder.

Individuals with bipolar disorder (BD) have a greater suicide risk than the general population. In this study, we employed latent profile analysis (LPA) to explore whether Chinese individuals with different phases of BD differed at the levels of suicidal ideation. We recruited 517 patients. Depressive symptoms were measured using the 24-item Hamilton Depression Rating Scale (HAMD-24), and manic symptoms were evaluated using the Young Mania Rating Scale (YMRS). The extent of suicidal thoughts was determined through the Beck Scale for Suicide Ideation (BSSI). The scores of HAMD and YMRS were used to perform LPA. LPA categorized participants into three classes: one exhibiting severe depressive and mild manic symptomatology, another showing severe depressive and severe manic symptomatology, and the third one displaying severe depressive and intermediate manic symptomatology. Suicidal ideation levels were found to be remarkably elevated across all three classes. Additionally, the three classes showed no significant differences in terms of suicidal ideation. Our research confirms the link between depressive symptoms and suicide, independent of the manic symptoms. These findings carry meaning as they provide insight into the suicide risk profiles within different phases of BD.

Effect of antipsychotics and mood stabilisers on metabolism in bipolar disorder: a network meta-analysis of randomised-controlled trials.

Background: Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Methods: Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Findings: Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA = 90.7%) and serum insulin (SUCRA = 96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA = 82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA = 93.3%), TG (SUCRA = 89.6%), and LDL (SUCRA = 94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA = 82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA = 100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Interpretation: Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. Funding: The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).

Clinical Characteristics of Asymptomatic Thromboembolism in Psychiatric Inpatients: A Retrospective Study.

Purpose: Venous thromboembolism (VTE) poses a significant threat to individuals' health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE. Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings. Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 µg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05). Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.

The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance.

AIMS: Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. METHODS: A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1-2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway. RESULTS: A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1-2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues. CONCLUSION: The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1-2 could enhance therapeutic strategies and improve PC patient outcomes.

The role of CD4+ T cells in tumor and chronic viral immune responses.

Immunotherapies are mainly aimed to promote a CD8+ T cell response rather than a CD4+ T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4+ T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4+ T cells relay help signals through dendritic cells to indirectly regulate CD8+ T cell response, interact with B cells or macrophages to indirectly modulate humoral immunity or macrophage polarization, and inhibit tumor blood vessel formation. Additionally, CD4+ T cells can also exhibit direct cytotoxicity toward target cells. However, regulatory T cells exhibit immunosuppression and CD4+ T cells become exhausted, which promote tumor progression and chronic viral persistence. Finally, we also outline immunotherapies based on CD4+ T cells, including adoptive cell transfer, vaccines, and immune checkpoint blockade. Overall, this review summarizes diverse roles of CD4+ T cells in the antitumor or protumor and chronic viral responses, and also highlights the immunotherapies based on CD4+ T cells, giving a better understanding of their roles in tumors and chronic viral infections.

DDX18 drives tumor immune escape through transcription-activated STAT1 expression in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) resists to current treatments due to its inherent tumor heterogeneity, therapy-resistant cancer stem/initiating cells survival, and immune evasion in the immunosuppressive tumor microenvironment (TME). Here, the results show that clinical PDAC and adjacent tissues undergo distinct chromatin remodeling. Multiple omics analysis revealed DEAD-box RNA helicase 18 (DDX18), a carcinogenic gene with similar H3K4me3 profile, is up-regulated and correlates with poor survival in PDAC patients. We validated that DDX18 deposits on the STAT1 promoter region and counteracts H3K27me3 deposition on the STAT1 promoter sequence by modulating the formation of the PRC2 complex to up-regulate the expression of STAT1, which results in the up-regulation of PD-L1 expression, T lymphocyte accumulation and overactivation in the highly desmoplastic and immunosuppressive pancreatic TME. DDX18-STAT1 axis inhibition also affects stemness of cancer cells, epithelial-mesenchymal transition (EMT) and disrupts the immunosuppressive TME simultaneously, producing sustained remissions of aggressive PDAC by synergizing with anti-PD-L1 therapy. Combining DDX18 inhibition with anti-PD-L1 immunochemotherapy to treat PDAC patients will pave a new way for clinical treatment of patients with PDAC. This study found that clinical PDAC and adjacent pancreatic tissues undergo distinct chromatin remodeling featured by the upregulation of DEAD-box RNA helicase 18 (DDX18). We further validated that DDX18 deposits on the STAT1 promoter region and counteracts H3K27me3 deposition on the STAT1 promoter by modulating the formation of the PRC2 complex to up-regulate the expression of STAT1. DDX18-STAT1 axis enhances the stemness of cancer cells, the upregulation of PD-L1 expression, T lymphocyte accumulation and overactivation in the highly desmoplastic and immunosuppressive pancreatic TME.

Corrigendum: The m6A methyltransferase METTL16 inhibits the proliferation of pancreatic adenocarcinoma cancer cells via the p21 signaling pathway.

[This corrects the article DOI: 10.3389/fonc.2023.1138238.].

Association of Tumor Cell Metabolic Subtype and Immune Response With the Clinical Course of Hepatocellular Carcinoma.

AIM: Tumor metabolism plays an important role in tumorigenesis and tumor progression. This study evaluated the potential association of tumor cell metabolism and immune cell tumor infiltration with the clinical course of hepatocellular carcinoma (HCC). METHODS: Gene-wise normalization and principal component analysis were performed to evaluate the metabolic system. A tumor microenvironment score system of tumor immune cell infiltration was constructed to evaluate its association with metabolic subtypes. Finally, we analyzed the impact of metabolism and immune cell infiltration on the clinical course of HCC. RESULTS: A total of 673 HCC patients were categorized into cholesterogenic (25.3%), glycolytic (14.6%), mixed (10.4%), and quiescent (49.8%) types based on glycolysis and cholesterol biosynthesis gene expression. The subgroups including the glycolytic genotyping expression (glycolytic and mixed types) showed a higher mortality rate. The glycolytic, cholesterogenic, and mixed types were positively correlated with M0 macrophage, resting mast cell, and naïve B-cell infiltration (P = .013, P = .019, and P = .006, respectively). In TCGA database, high CD8+ T cell and low M0 macrophage infiltration were associated with prolonged overall survival (OS, P = .0017 and P < .0001, respectively). Furthermore, in glycolytic and mixed types, patients with high M0 macrophage infiltration had a shorter OS (P = .03 and P = .013, respectively), and in quiescent type, patients with low naïve B-cell infiltration had a longer OS (P = .007). CONCLUSIONS: Tumor metabolism plays a prognostic role and correlates with immune cell infiltration in HCC. M0 macrophage and CD8+ T cell appear to be promising prognostic biomarker for HCC. Finally, M0 macrophages may represent a useful immunotherapeutic target in patients with HCC.

The m6A methyltransferase METTL16 inhibits the proliferation of pancreatic adenocarcinoma cancer cells via the p21 signaling pathway.

Background: Many studies have reported that N6-methyladenosine (m6A) modification plays a critical role in the epigenetic regulation of organisms and especially in the pathogenesis of malignant diseases. However, m6A research has mainly focused on methyltransferase activity mediated by METTL3, and few studies have focused on METTL16. The aim of this study was to investigate the mechanism of METTL16, which mediates m6A modification, and its role in pancreatic adenocarcinoma (PDAC) cell proliferation. Methods: Clinicopathologic and survival data were retrospectively collected from 175 PDAC patients from multiple clinical centers to detect the expression of METTL16. CCK-8, cell cycle, EdU and xenograft mouse model experiments were used to evaluate the proliferation effect of METTL16. Potential downstream pathways and mechanisms were explored via RNA sequencing, m6A sequencing, and bioinformatic analyses. Regulatory mechanisms were studied through methyltransferase inhibition, RIP, MeRIP‒qPCR assays. Results: We found that METTL16 expression was markedly downregulated in PDAC, and multivariate Cox regression analyses revealed that METTL16 was a protective factor for PDAC patients. We also demonstrated that METTL16 overexpression inhibited PDAC cell proliferation. Furthermore, we identified a METTL16-p21 signaling axis, with downregulation of METTL16 resulting in inhibition of CDKN1A (p21). Additionally, METTL16 silencing and overexpression experiments highlighted m6A modification alterations in PDAC. Conclusions: METTL16 plays a tumor-suppressive role and suppresses PDAC cell proliferation through the p21 pathway by mediating m6A modification. METTL16 may be a novel marker of PDAC carcinogenesis and target for the treatment of PDAC.

Duodenum-preserving pancreatic head resection compared to pancreaticoduodenectomy: A systematic review and network meta-analysis of surgical outcomes.

Objectives: In this systemic review and network meta-analysis, we investigated pancreaticoduodenectomy (PD), pylorus-preserving pancreaticoduodenectomy (PPPD), and different modifications of duodenum-preserving pancreatic head resection (DPPHR) to evaluate the efficacy of different surgical procedures. Methods: A systemic search of six databases was conducted to identify studies comparing PD, PPPD, and DPPHR for treating pancreatic head benign and low-grade malignant lesions. Meta-analyses and network meta-analyses were performed to compare different surgical procedures. Results: A total of 44 studies were enrolled in the final synthesis. Three categories of a total of 29 indexes were investigated. The DPPHR group had better working ability, physical status, less loss of body weight, and less postoperative discomfort than the Whipple group, while both groups had no differences in quality of life (QoL), pain scale scores, and other 11 indexes. Network meta-analysis of a single procedure found that DPPHR had a larger probability of best performance in seven of eight analyzed indexes than PD or PPPD. Conclusion: DPPHR and PD/PPPD have equal effects on improving QoL and pain relief, while PD/PPPD has more severe symptoms and more complications after surgery. PD, PPPD, and DPPHR procedures exhibit different strengths in treating pancreatic head benign and low-grade malignant lesions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022342427.

CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis.

BACKGROUND: Growing evidences suggest that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell, and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion, and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft model was constructed for in vivo experiment. RESULTS: CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promotes the progression of PDAC. CONCLUSIONS: This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.

Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characteristics in pancreatic adenocarcinoma.

BACKGROUND: Multiple molecular subtypes with distinct clinical outcomes in pancreatic adenocarcinoma (PAAD) have been identified in recent years. Cuproptosis is a new form of cell death that likely involved in tumor progression. However, the cuproptosis-related molecular subtypes as well as its mediated tumor microenvironment (TME) cell infiltration characteristics largely remain unclear. METHODS: Expression profiles of 10 cuproptosis-related genes (CRGs) and their association with patient survival, TME, cancer stemness and drug resistance were studied in 33 cancer types using the TCGA pan-cancer data. Using 437 PAAD samples from five cohorts (TCGA-PAAD cohort and four GEO cohorts), we explored the molecular subtypes mediated by CRGs, along with the associated TME cell infiltration. Unsupervised methods were utilized to perform cuproptosis subtype clustering. The cuproptosis score was constructed using the COX regression model with least absolute shrinkage and selection operator regression (LASSO) algorithm to quantify the cuproptosis characteristics of a single tumor. RESULTS: The expression of 10 CRGs varies in different cancer types with striking inter- and intra- cancer heterogeneity. We integrated the genomic profiling of the CRGs and identified three distinct cuproptosis subtypes, and found that multi-layer CRG alterations were correlated with patient prognosis and TME cell infiltration characteristics. In addition, a cuproptosis score signature was constructed to predict prognosis, and its clinical impacts were characterized in the TCGA-PAAD cohort. The cuproptosis signature was significantly associated with prognosis, tumor subtypes, CD8 T-cell infiltration, response to immune checkpoint inhibitors (ICIs) and chemotherapeutic drug sensitivity. Furthermore, the expression patterns of CRGs in pancreatic cancer cells and normal controls were validated, which was almost consistent with the results from the public database. The expression level and prognostic predictive capability of DLAT were verified in 97 PAAD patients from our patient cohort. CONCLUSIONS: These findings may help understand the roles of CRGs in PAAD and the molecular characterization of cuproptosis subtypes. In addition, the cuproptosis score could serve as a promising biomarker for predicting prognosis and response to immunotherapy in PAAD patients.

Development and validation of a novel ferroptosis­related lncRNA prognostic signature for pancreatic adenocarcinoma.

Long non­coding RNAs (lncRNAs) serve a pivotal role in the regulation of cancer cell ferroptosis. However, the prognostic value of ferroptosis­related lncRNAs in pancreatic adenocarcinoma (PAAD) largely remains unclear. We aimed at constructing a lncRNA­based signature to improve the prognosis prediction of PAAD. In the present study, the transcriptome profiling data and clinical information of patients with PAAD were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Gene Consortium (ICGC) databases. Univariate Cox regression analysis of the TCGA cohort demonstrated that 26 ferroptosis­related lncRNAs had significant prognostic value for PAAD (all P<0.01). Least absolute shrinkage and selection operator regression and multivariate Cox proportional hazards regression analyses were performed to construct a prognostic ferroptosis­related lncRNA signature (FRLS) comprising nine ferroptosis­related lncRNAs. The efficacy of this FRLS was verified in the training (TCGA) and validation (ICGC) cohorts. Based on the risk model, high risk scores were significantly correlated with poor overall survival (OS) (hazard ratio, 1.314; 95% confidence interval, 1.218­1.418; P<0.001). The receiver operating characteristic curves and principal component analysis further demonstrated the robust prognostic ability of the FRLS. Furthermore, a nomogram with favorable predictive efficacy for the prediction of OS was constructed based on the FRLS and clinical features. Gene set enrichment analysis demonstrated that the genes in the FRLS participated in a number of cancer­associated immunoregulatory pathways. Importantly, it was demonstrated that immune infiltration and response to cancer immunotherapy differed significantly between the high and low­risk groups according to the FRLS. In conclusion, the risk signature based on the FRLS has potential for the clinical prediction of prognosis and immunotherapy response in patients with PAAD.

Increased expression of miR-194-5p through the circPVRL3/miR-194-5p/SOCS2 axis promotes proliferation and metastasis in pancreatic ductal adenocarcinoma by activating the PI3K/AKT signaling pathway.

BACKGROUND: MicroRNAs (miRNAs), as an indispensable type of non-coding RNA (ncRNA), participate in diverse biological processes. However, the specific regulatory mechanism of certain miRNAs in pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: The expression of miR-194-5p in PDAC tissue microarray and cell lines were detected by RNA-scope and real-time quantitative PCR (RT-qPCR). The function of proliferation and migration carried by miR-194-5p in vitro and vivo was observed by several functional experiments. Informatics methods and RNA sequencing data were applied to explore the target of miR-194-5p and the upstream circular RNA (circRNA) of miR-194-5p. RNA-binding protein immunoprecipitation (RIP) assay and dual-luciferase reporter assay confirmed the relationships between miR-194-5p and SOCS2 or miR-194-5p and circPVRL3. The proliferation and migration abilities of SOCS2 and circPVRL3 were accessed by rescue experiments. RESULTS: In this study, we aimed to clarify the molecular mechanisms of miR-194-5p, which has critical roles during PDAC progression. We found that the expression of miR-194-5p was significantly upregulated in PDAC tissue compared to tumor-adjacent tissue and was highly related to age and nerve invasion according to RNAscope and RT‒qPCR. Overexpression of miR-194-5p accelerated the cell cycle and enhanced the proliferation and migration processes according to several functional experiments in vitro and in vivo. Specifically, circPVRL3, miR-194-5p, and SOCS2 were confirmed to work as competing endogenous RNAs (ceRNAs) according to informatics methods, RIP, and dual-luciferase reporter assays. Additionally, the rescue experiments confirmed the relationship among miR-194-5p, circPVRL3, and SOCS2 mRNA. Finally, the circPVRL3/miR-194-5p/SOCS2 axis activates the PI3K/AKT signaling pathway to regulate the proliferation and metastasis of PDAC. CONCLUSION: Our findings indicated that an increase of miR-194-5p caused by circPVRL3 downregulation stimulates the PI3K/AKT signaling pathway to promote PDAC progression via the circPVRL3/miR-194-5p/SOCS2 axis, which suggests that the circPVRL3/miR-194-5p/SOCS2 axis may be a potential therapeutic target for PDAC patients.

Long-Term Effect of Pancreaticoduodenectomy Combined with Revascularization for Resectable Pancreatic Carcinoma in Elderly Patients.

BACKGROUND Pancreaticoduodenectomy combined with revascularization (PDR) is the main surgical procedure for resectable pancreatic ductal adenocarcinoma (PDAC) with venous system invasion, but this procedure is discouraged in elderly patients because of physical complexity. Our aim was to explore the differences of perioperative and survival in patients of different ages who underwent PDR. MATERIAL AND METHODS We reviewed data from PDAC patients undergoing PDR from 2007 to 2018. Patients were subdivided into 3 groups according to age: <60 years, 60-70 years, and ≥70 years. Postoperative complications and long-term survival were compared among the 3 groups. RESULTS From 626 patients, 185 had en bloc venous resection who underwent PDR (103, 55, and 27 patients from young to elderly). Increasing age was linked to a higher prevalence of ICU management (P=0.035) and more serious complications (grade ≥III, P=0.043); overall mortality was 8.1% and did not significantly differ among age-matched groups. Further, there was no difference in overall survival (OS) or progression-free survival (PFS) based on age (<60, 60-70, ≥70, median OS were 9.7, 8.4 vs 9.1 months, respectively, P=0.787; median PFS were 6.9, 6.1 vs 8.4 months, respectively, P=0.603). However, patients <60 years whose tumors invaded the superior mesenteric vascular had better survival outcomes when compared with the other 2 groups (11.5 vs 8.4, 9.1 months, P=0.049). CONCLUSIONS The results show that age should not be considered an absolute contraindication for PDR, as elderly patients can achieve the same surgical efficacy and long-term survival prognosis.

Repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy treatment in alcohol-dependent patients: A randomized, double-blind sham-controlled multicenter clinical trial.

Background: Alcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD. Materials and methods: A total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse. Results: The sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan-Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05). Conclusion: This study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

Right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery for the treatment of intrahepatic HHT: A case report.

Hereditary haemorrhagic telangiectasia (HHT) is a rare disease that lacks effective treatment. Here, the authors report the case of a 30-year-old woman presenting with abdominal pain accompanied by severe malnutrition. After a definite diagnosis of HHT involvement in the liver, liver transplantation was the first-choice treatment according to the guidelines of HHT. However, the patient firmly refused liver transplantation. Finally, a new type of surgery, right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery, was performed based on careful study of the case and with the maximum benefit of the patient in mind. Although the patient developed transient liver dysfunction after surgery, she eventually recovered well and continued to be followed up. As far as we know, this is the first report of this kind of surgery for the treatment of intrahepatic HHT.

Novel Bimetallic Activated Center Alloying Mechanism Positive Electrodes for Aluminum Storage.

Aluminum is the most abundant metal element in the Earth's crust, thus developing the rechargeable aluminum-ion batteries (AIBs) provides an ideal opportunity to realize cells with pleasing energy-to-price ratios. However, the further development of AIBs is plagued by the scarcity of suitable positive electrode materials. Here, for the first time, a tin-based alloy positive electrode material for AIBs, Co3 Sn2 wrapped with graphene oxide (Co3 Sn2 @GO composite) is well-designed and investigated to understand the aluminum storage behavior. A series of experimental measurements and theoretical calculations results reveal that a novel "bimetallic activated center alloying reaction" aluminum storage mechanism is occurred on the prepared Co3 Sn2 positive electrode. The reversible alloying/de-alloying process in AlCl3 /[EMIm]Cl ionic liquid, where both Co and Sn in Co3 Sn2 alloys react electrochemically with Al3+ to form Alx Sn and Aly Co is first put forward. This study delineates new insights on the aluminum storage mechanism, which may guide to ultimately exploit the energy benefits of "bimetallic activated center alloying redox".

Stabilization of Cu+ via Strong Electronic Interaction for Selective and Stable CO2 Electroreduction.

Copper oxide-based materials effectively electrocatalyze carbon dioxide reduction (CO2 RR). To comprehend their role and achieve high CO2 RR activity, Cu+ in copper oxides must be stabilized. As an electrocatalyst, Cu2 O nanoparticles were decorated with hexagonal boron nitride (h-BN) nanosheets to stabilize Cu+ . The C2 H4 /CO ratio increased 1.62-fold in the CO2 RR with Cu2 O-BN compared to that with Cu2 O. Experimental and theoretical studies confirmed strong electronic interactions between the two components in Cu2 O-BN, which strengthens the Cu-O bonds. Electrophilic h-BN receives partial electron density from Cu2 O, protecting the Cu-O bonds from electron attack during the CO2 RR and stabilizing the Cu+ species during long-term electrolysis. The well-retained Cu+ species enhanced the C2 product selectivity and improved the stability of Cu2 O-BN. This work offers new insight into the metal-valence-state-dependent selectivity of catalysts, enabling the design of advanced catalysts.