Enhancing wound healing and overcoming cisplatin resistance in ovarian cancer.

Ovarian cancer (OC) poses significant oncological challenges, notably impaired wound healing in the context of cisplatin (DDP) resistance. This study investigates the role of miR-200b in OC, emphasizing its impact on wound healing processes through DNMT3A/TGF-ß1 pathway. The primary aim was to explore how miR-200b regulates autophagy and its consequential effects on wound healing in OC, alongside its influence on cisplatin resistance. Utilizing DDP-sensitive (A2780) and resistant (A2780/DDP) OC cell lines, along with human fibroblast cultures, the study employed an array of in vitro techniques. These included cell transfection with miR-200b mimic or inhibitor, chromatin immunoprecipitation (ChIP), dual-luciferase reporter (DLR) assays, quantitative PCR, Western blotting, MTT and particularly, wound healing assays. The research highlighted the role of miR-200b in wound healing within OC. Inhibition of miR-200b in A2780 cells and its mimic in A2780/DDP cells affected cell viability, indicating the link with DDP resistance. Crucially, miR-200b mimic significantly delayed fibroblast-mediated wound closure in assays, underscoring its impact on wound healing. Bioinformatics analysis and subsequent DLR assays confirmed miR-200b's interaction with DNMT3A, affecting TGF-ß1 expression, the key factor in wound repair. Further, ChIP, quantitative PCR and Western blot analyses validated the interaction and expression changes in DNMT3A and TGF-ß1. The study demonstrated that miR-200b played a pivotal role in OC by modulating autophagy, which in turn significantly affected wound healing through the DNMT3A/TGF-ß1 pathway.

Approaches of laparoscopic anatomical liver resection of segment 8 for hepatocellular carcinoma: a retrospective cohort study of short-term results at multiple centers in China.

BACKGROUND: Laparoscopic anatomical liver resection of segment 8 (LALR-S8) remains a challenge for anatomical laparoscopic segmentectomy. Most current reports on LALR-S8 are case series using one surgical approach, and there is a lack of multicenter data on identifying intersegmental planes using different approaches. In this study, the authors aimed to elucidate the short-term results of three different approaches for LALR-S8 for hepatocellular carcinoma (HCC), focusing on intersegmental plane determination, and to reflect on current practice regarding different approaches at multiple centers in China. MATERIALS AND METHODS: The clinical cohort data of 122 patients who underwent LALR-S8 for HCC at seven leading centers in China were retrospectively analyzed. The surgical procedures of all approaches were summarized and standardized according to the method of the Glissonean pedicle of segment 8 identification. The postoperative short-term outcomes and oncological results of the three approaches were evaluated and compared. RESULTS: Three approaches were used: laparoscopic ultrasonography-guided indocyanine green fluorescent positive staining approach (11/122, 9.02%), hepatic vein-guided approach (99/122, 81.15%), and Glissonean indocyanine green fluorescent negative staining approach (12/122, 9.83%). Seven (5.73%) patients experienced complications according to the Clavien-Dindo classification, and the rate of grade ≥IIIa complications was 2.46%. The R0 resection rates among the groups (margin >1 mm) and the margin width showed no statistical difference. CONCLUSION: LALR-S8 is safe and feasible for treating HCC under standardized surgical techniques and appropriate surgical approaches. The three reported approaches had comparable short-term oncological outcomes, while the hepatic vein-guided approach was most commonly used.

Safety and efficacy of postoperative adjuvant therapy with atezolizumab and bevacizumab after radical resection of hepatocellular carcinoma.

BACKGROUND: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors. METHODS: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed. RESULTS: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy. CONCLUSION: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications.

Nonalcoholic steatohepatitis critically rewires the ischemia/reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice.

Background: Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis (NASH), which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion (I/R) injury. However, the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified. Methods: The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH, then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury. Untargeted lipidomics were performed to determine hepatic lipids in NASH livers with I/R injury through ultra-high performance liquid chromatography coupled with mass spectrometry. The pathology associated with the dysregulated lipids was examined. Results: Lipidomics analyses identified cardiolipins (CL) and sphingolipids (SL), including ceramides (CER), glycosphingolipids, sphingosines, and sphingomyelins, as the most relevant lipid classes that characterized the lipid dysregulation in NASH livers with I/R injury. CER were increased in normal livers with I/R injury, and the I/R-induced increase of CER was further augmented in NASH livers. Metabolic pathway analysis revealed that the enzymes involved in the synthesis and degradation of CER were highly upregulated in NASH livers with I/R injury, including serine palmitoyltransferase 3 (Sptlc3), ceramide synthase 2 (Cers2), neutral sphingomyelinase 2 (Smpd3), and glucosylceramidase beta 2 (Gba2) that produced CER, and alkaline ceramidase 2 (Acer2), alkaline ceramidase 3 (Acer3), sphingosine kinase 1 (Sphk1), sphingosine-1-phosphate lyase (Sgpl1), and sphingosine-1-phosphate phosphatase 1 (Sgpp1) that catalyzed the degradation of CER. CL were not affected by I/R challenge in normal livers, but CL was dramatically reduced in NASH livers with I/R injury. Consistently, metabolic pathway analyses revealed that the enzymes catalyzing the generation of CL were downregulated in NASH-I/R injury, including cardiolipin synthase (Crls1) and tafazzin (Taz). Notably, the I/R-induced oxidative stress and cell death were found to be aggravated in NASH livers, which were possibly mediated by the reduction of CL and accumulation of CER. Conclusions: The I/R-induced dysregulation of CL and SL were critically rewired by NASH, which might potentially mediate the aggressive I/R injury in NASH livers.

Integrative epigenetic analysis reveals AP-1 promotes activation of tumor-infiltrating regulatory T cells in HCC.

Regulatory T (Treg) cells that infiltrate human tumors exhibit stronger immunosuppressive activity compared to peripheral blood Treg cells (PBTRs), thus hindering the induction of effective antitumor immunity. Previous transcriptome studies have identified a set of genes that are conserved in tumor-infiltrating Treg cells (TITRs). However, epigenetic profiles of TITRs have not yet been completely deciphered. Here, we employed ATAC-seq and CUT&Tag assays to integrate transcriptome profiles and identify functional regulatory elements in TITRs. We observed a global difference in chromatin accessibility and enhancer landscapes between TITRs and PBTRs. We identified two types of active enhancer formation in TITRs. The H3K4me1-predetermined enhancers are poised to be activated in response to tumor microenvironmental stimuli. We found that AP-1 family motifs are enriched at the enhancer regions of TITRs. Finally, we validated that c-Jun binds at regulatory regions to regulate signature genes of TITRs and AP-1 is required for Treg cells activation in vitro. High c-Jun expression is correlated with poor survival in human HCC. Overall, our results provide insights into the mechanism of AP-1-mediated activation of TITRs and can hopefully be used to develop new therapeutic strategies targeting TITRs in liver cancer treatment.

HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway.

BACKGROUND: Hepatic inflammation is a common initiator of liver diseases and considered as the primary driver of hepatocellular carcinoma (HCC). However, the precise mechanism of inflammation-induced HCC development and immune evasion remains elusive and requires extensive investigation. This study sought to identify the new target that is involved in inflammation-related liver tumorigenesis. METHODS: RNA-sequencing (RNA-seq) analysis was performed to identify the differential gene expression signature in primary human hepatocytes treated with or without inflammatory stimulus. A giant E3 ubiquitin protein ligase, HECT domain and RCC1-like domain 2 (HERC2), was identified in the analysis. Prognostic performance in the TCGA validation dataset was illustrated by Kaplan-Meier plot. The functional role of HERC2 in HCC progression was determined by knocking out and over-expressing HERC2 in various HCC cells. The precise molecular mechanism and signaling pathway networks associated with HERC2 in HCC stemness and immune evasion were determined by quantitative real-time PCR, immunofluorescence, western blot, and transcriptomic profiling analyses. To investigate the role of HERC2 in the etiology of HCC in vivo, we applied the chemical carcinogen diethylnitrosamine (DEN) to hepatocyte-specific HERC2-knockout mice. Additionally, the orthotopic transplantation mouse model of HCC was established to determine the effect of HERC2 during HCC development. RESULTS: We found that increased HERC2 expression was correlated with poor prognosis in HCC patients. HERC2 enhanced the stemness and PD-L1-mediated immune evasion of HCC cells, which is associated with the activation of signal transducer and activator of transcription 3 (STAT3) pathway during the inflammation-cancer transition. Mechanically, HERC2 coupled with the endoplasmic reticulum (ER)-resident protein tyrosine phosphatase 1B (PTP1B) and limited PTP1B translocation from ER to ER-plasma membrane junction, which ameliorated the inhibitory role of PTP1B in Janus kinase 2 (JAK2) phosphorylation. Furthermore, HERC2 knockout in hepatocytes limited hepatic PD-L1 expression and ameliorated HCC progression in DEN-induced mouse liver carcinogenesis. In contrast, HERC2 overexpression promoted tumor development and progression in the orthotopic transplantation HCC model. CONCLUSION: Our data identified HERC2 functions as a previously unknown modulator of the JAK2/STAT3 pathway, thereby promoting inflammation-induced stemness and immune evasion in HCC.

Characterization of somatic mutations and pathway alterations during hepatocellular carcinoma vascular invasion using next-generation sequencing.

Background: Vascular invasion is an independent risk factors for recurrence and poor prognosis in patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms of HCC vascular invasion are largely unknown. Deciphering the molecular changes associated with the vascular invasion process will aid in the identification of therapeutic targets and treatment for patients with HCC. Methods: DNA was extracted from tumor specimens and blood samples collected from 50 patients with HCC. Next-generation sequencing (NGS) was performed to detect HCC gene variants. Bioinformatics methods were used to comprehensively analyze the three sets of sequencing data grouped by vascular invasion, including differences in tumor mutation burden (TMB), mutation characteristics, and alterations in signaling pathways. Results: Bioinformatics analysis detected a total of 762 single nucleotide variants (SNVs). The TMB was not significantly different between patients with macrovascular invasion, microvascular invasion (MVI), or avascular invasion. Ten genes related to prognosis or recurrence, and one oncogene related to vascular invasion were screened. Compared with the avascular invasion cluster, the variant genes in the macrovascular and MVI clusters were mainly enriched in the thyroid hormone signaling pathway. In addition, macrovascular invasion variant genes were also enriched in the insulin signaling pathway and the Fanconi anemia pathway. Conclusions: Somatic mutations and pathway changes associated with vascular invasion in HCC were identified. The discovery of the molecular drivers of vascular invasion in HCC provides novel insights that can help guide further patient diagnosis and personalized therapy.

A multimodal model fusing multiphase contrast-enhanced CT and clinical characteristics for predicting lymph node metastases of pancreatic cancer.

Objective.To develop a multimodal model that combines multiphase contrast-enhanced computed tomography (CECT) imaging and clinical characteristics, including experts' experience, to preoperatively predict lymph node metastasis (LNM) in pancreatic cancer patients.Methods.We proposed a new classifier fusion strategy (CFS) based on a new evidential reasoning (ER) rule (CFS-nER) by combining nomogram weights into a previous ER rule-based CFS. Three kernelled support tensor machine-based classifiers with plain, arterial, and venous phases of CECT as the inputs, respectively, were constructed. They were then fused based on the CFS-nER to construct a fusion model of multiphase CECT. The clinical characteristics were analyzed by univariate and multivariable logistic regression to screen risk factors, which were used to construct correspondent risk factor-based classifiers. Finally, the fusion model of the three phases of CECT and each risk factor-based classifier were fused further to construct the multimodal model based on our CFS-nER, named MMM-nER. This study consisted of 186 patients diagnosed with pancreatic cancer from four clinical centers in China, 88 (47.31%) of whom had LNM.Results.The fusion model of the three phases of CECT performed better overall than single and two-phase fusion models; this implies that the three considered phases of CECT were supplementary and complemented one another. The MMM-nER further improved the predictive performance, which implies that our MMM-nER can complement the supplementary information between CECT and clinical characteristics. The MMM-nER had better predictive performance than based on previous classifier fusion strategies, which presents the advantage of our CFS-nER.Conclusion.We proposed a new CFS-nER, based on which the fusion model of the three phases of CECT and MMM-nER were constructed and performed better than all compared methods. MMM-nER achieved an encouraging performance, implying that it can assist clinicians in noninvasively and preoperatively evaluating the lymph node status of pancreatic cancer.

Rehabilitation effect of tennis on patients with elbow joint injury / Efeito reabilitador do tênis em pacientes com lesões na articulação do joelho / Efecto rehabilitador del tenis en pacientes con lesiones en la articulación de la rodilla

ABSTRACT Introduction: Knee joint injuries are common, and their pathogenesis is complex. Objective: To study the rehabilitation effect of tennis on patients with joint injury. Methods: We use literature, a questionnaire, and other research methods to investigate the joint injuries of 126 athletes who participated in the 19th University Tennis Championships in 2014. We use sports anatomy knowledge combined with tennis special techniques for analysis. Results: The rehabilitation group was better than the control group (p<0.01) in curative effect, duration of the knee pain, time until ligament reconstruction happened, knee joint movement range, knee joint movement pain degree, lower limb walking function score, and self-care ability. There was no statistical difference in accidental injuries between the two groups (p>0.05). Conclusions: When compared to conventional methods, the rehabilitation program was effective in treating knee joint sports injuries. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Lesões na articulação do joelho são comuns, e sua patogênese, complexa. Objetivo: Estudar o efeito reabilitador do tênis em pacientes com lesões na articulação. Método: Esta pesquisa utiliza revisão bibliográfica, questionário, e outros métodos para investigar lesões nas articulações de 126 atletas que participaram do 19º Campeonato de Tênis Universitário em 2014. Utilizamos conhecimentos de anatomia aplicada ao esporte combinados com técnicas especiais do tênis para as análises. Resultados: Os resultados do grupo que passou pela reabilitação foram superiores (p<0,01) em efeito curativo, duração da dor no joelho, tempo até a reconstrução do ligamento do joelho, amplitude de movimento na articulação do joelho, nível de dor ao movimentar a articulação do joelho, score da função de marcha, e em sua habilidade para o autocuidado. Não houve diferença estatística no que diz respeito a ferimentos acidentais entre os dois grupos (p>0,05). Conclusão: O programa de reabilitação foi mais eficiente no tratamento de lesões da articulação do joelho causadas durante a prática de esportes. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: La lesiones en la articulación de la rodilla son comunes y su patogénesis es compleja. Objetivo: Estudiar el efecto rehabilitador del deporte tenis en pacientes con lesiones en la articulación. Método: Esta investigación utiliza revisión bibliográfica, cuestionario y otros métodos para investigar lesiones en las articulaciones de 126 atletas que participaron en el 19º Campeonato de Tenis Universitario en 2014. Utilizamos conocimientos de anatomía aplicada al deporte combinados con técnicas especiales del tenis para los análisis. Resultados: Los resultados del grupo que pasó por la rehabilitación fueron superiores (p<0,01) en efecto curativo, duración del dolor en la rodilla, tiempo hasta la reconstrucción del ligamento de la rodilla, amplitud del movimiento en la articulación de la rodilla, nivel de dolor al mover la articulación de la rodilla, score de la función de marcha y en su habilidad para autocuidado. No hubo diferencia estadística en lo que respecta a las heridas accidentales entre los dos grupos (p>0,05). Conclusión: El programa de rehabilitación fue más eficiente en el tratamiento de lesiones de la articulación de la rodilla causadas durante la práctica de deportes. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Systematic review and meta-analysis: the effect and safety of peritoneal dialysis in patients with end-stage diabetic kidney disease.

BACKGROUND: At present, peritoneal dialysis (PD) is widely used in the clinical treatment of patients with end-stage renal disease (ESRD), and comparison of the efficacy of PD and hemodialysis (HD) in the treatment of diabetic kidney disease (DKD) has been reported in a few clinical studies. METHODS: In this study, "dialysis", "peritoneal dialysis", "renal replacement therapy", "end-stage renal disease", "diabetic renal disease", and "efficacy and safety" were used as search terms in Chinese and English databases. According to RevMan 5.3 and Stata 13 software provided by the Cochrane Collaboration, a meta-analysis was performed. RESULTS: Four randomized controlled trials were included in this study, and 3 trials described the randomization method, 3 described allocation concealment in detail, and 2 used the blinding method. Compared with the HD treatment in the control group, the PD treatment in the experimental group can significantly reduce the hemoglobin of patients with end-stage DKD [Mean difference (MD) =-0.13, 95% confidence interval (CI): -0.21 to -0.04; P=0.003<0.05] and Albumin level (MD = -0.10, 95% CI: -0.16 to -0.04; P=0.002<0.05). Compared with the control group, the PD treatment in the experimental group significantly increased the serum creatinine and blood urea nitrogen levels in patients with end-stage DKD, but there was no significant difference in the effects of PD and HD treatment on serum creatinine levels (MD =-0.30, 95% CI: -0.77 to 0.16; P=0.20>0.05), (MD =1.93, 95% CI: -2.65 to 6.51; P=-0.41>0.05). In addition, PD treatment in the experimental group significantly increased the probability of malignant tumors in patients with end-stage DKD [odds ratio (OR) =1.86, 95% CI: 1.64 to 2.10; P<0.00001], and the difference was significant. DISCUSSIONS: This study used meta-analysis to confirm that PD can significantly improve the renal function of patients with end-stage DKD, but it can also increase the probability of protein loss and complications.

Transcriptome analysis reveals the potential biological function of FSCN1 in HeLa cervical cancer cells.

Fascin actin-bundling protein 1 (FSCN1), an actin-bundling protein associated with cell migration and invasion, is highly expressed in various tumor tissues. FSCN1 has also been reported to be a marker of increased invasive potential in cervical cancers. However, the functions of FSCN1 are still not fully understood in cervical cancers. Here, the gene expression profile of HeLa cells transfected with FSCN1 shRNA (shFSCN1) was compared with that of cells transfected with empty vector (shCtrl). The results showed that shFSCN1 extensively affected the transcription level of 5,043 genes in HeLa cells. In particular, Gene Ontology (GO) analysis showed that a large number of upregulated genes were annotated with terms including transcription regulation and DNA binding. The downregulated genes were enriched in some cancer pathways, including angiogenesis and cell adhesion. qPCR validation confirmed that FSCN1 knockdown significantly affected the expression of selected genes in HeLa cells either negatively or positively. Expression analysis in TCGA (The Cancer Genome Atlas) revealed that FSCN1 had negative correlations with several transcription factors and a positive correlation with an angiogenic factor (angiopoietin like 4, ANGPTL4) in cervical tumor tissue. In particular, validation by Western blotting showed that FSCN1 knockdown decreased the protein level of ANGPTL4. Our results demonstrated that FSCN1 is not only an actin-binding protein but also a transcriptional regulator and an angiogenic factor in cervical cancer. Thus, our study provides important insights for further study on the regulatory mechanism of FSCN1 in cervical cancer.

Source apportionment and risk assessment for polycyclic aromatic hydrocarbons in soils at a typical coking plant.

Polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment. The coking industry is an important industrial source of PAHs. Coke production in China accounts for 67.44% of total global coke production. Tangshan, a coastal city on the Bohai Rim, contains the largest cluster of coking plants in China. Extremely high PAH emissions in Tangshan may cause long-distance cross-border pollution problems. In this study, the concentrations and sources of 16 priority PAHs in soil at a coking plant in Tangshan were determined and the risks posed by the PAHs were assessed. The PAH concentrations were generally higher in surface soil than subsurface soil, particularly near the coke oven, crude benzol, and coal blending areas. The dibenz[a,h]anthracene (DBA) concentrations were higher than the risk screening value (1500 ngg-1) but lower than the control value (15,000 ngg-1) for type II land defined in Chinese standard (GB36600-2018). The main sources of PAHs were coal combustion, the coke oven, and traffic. The PAH concentrations were higher in the ammonium sulfate, boiler room, coal blending, and coke oven areas than in the other areas. Toxic equivalent concentrations were calculated to assess the toxic and carcinogenic risks posed by PAHs. The toxic equivalent concentrations were relatively high in the boiler, crude benzol, and coal blending areas, where the toxic equivalent concentrations for the sums of seven highly carcinogenic PAHs contributed 95% of the toxic equivalent concentrations for the sums of the 16 PAHs that were analyzed. The carcinogenic risks posed to humans were therefore assessed using the concentrations of the seven highly carcinogenic PAHs. Dermal contact was found to be an important exposure pathway leading to carcinogenic risks. The carcinogenic risk posed by DBA was > 1 × 10-6 but < 5 × 10-6, indicating that DBA concentrations at the study site monitored closely.

A Novel Post-Operative ALRI Model Accurately Predicts Clinical Outcomes of Resected Hepatocellular Carcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading malignant tumors worldwide. Prognosis and long-term survival of HCC remain unsatisfactory, even after radical resection, and many non-invasive predictors have been explored for post-operative patients. Most prognostic prediction models were based on preoperative clinical characteristics and pathological findings. This study aimed to investigate the prognostic value of a newly constructed nomogram, which incorporated post-operative aspartate aminotransferase to lymphocyte ratio index (ALRI). METHODS: A total of 771 HCC patients underwent radical resection from three medical centers were enrolled and grouped into the training cohort (n = 416) and validation cohort (n = 355). Prognostic prediction potential of ALRI was assessed by receiver operating curve (ROC) analysis. The Cox regression model was used to identify independent prognostic factors. Nomograms for overall survival (OS) and disease-free survival (DFS) were constructed and further validated externally. RESULTS: The ROC analysis ranked ALRI as the most effective prediction marker for resected HCC patients, with the cut-off value determined at 22.6. Higher ALRI level positively correlated with larger tumor size, higher tumor node metastasis (TNM) stage, and inversely with lower albumin level and shorter OS and DFS. Nomograms for OS and DFS were capable of discriminating HCC patients into different risk-groups. CONCLUSIONS: Post-operative ALRI was of prediction value for HCC prognosis. This novel nomogram may categorize HCC patients into different risk groups, and offer individualized surveillance reference for post-operative patients.

Integrated Proteomics and Bioinformatics to Identify Potential Prognostic Biomarkers in Hepatocellular Carcinoma.

BACKGROUND: Liver hepatocellular carcinoma (HCC) is the third most common cause of death by cancer and has a high mortality world-widely. Approximately 75-85% of primary liver cancers are caused by HCC. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient's outcome. OBJECTIVE: In this research, we aim to identify novel prognostic biomarkers in hepatocellular carcinoma. METHODS: Integrated proteomics and bioinformatics analysis were performed to investigate the expression landscape of prognostic biomarkers in 24 paired HCC patients. RESULTS: As a result, eight key genes related to prognosis, including ACADS, HSD17B13, PON3, AMDHD1, CYP2C8, CYP4A11, SLC27A5, CYP2E1, were identified by comparing the weighted gene co-expression network analysis (WGCNA), proteomic differentially expressed genes (DEGs), proteomic turquoise module, The Cancer Genome Atlas (TCGA) cohort DEGs of HCC. Furthermore, we trained and validated eight pivotal genes integrating these independent clinical variables into a nomogram with superior accuracy in predicting progression events, and their lower expression was associated with a higher stage/risk score. The Gene Set Enrichment Analysis (GSEA) further revealed that these key genes showed enrichment in the HCC regulatory pathway. CONCLUSION: All in all, we found that these eight genes might be the novel potential prognostic biomarkers for HCC and also provide promising insights into the pathogenesis of HCC at the molecular level.

Microscopic Tumour Classification by Digital Mammography.

In this paper, we investigate the classification of microscopic tumours using full digital mammography images. Firstly, to address the shortcomings of traditional image segmentation methods, two different deep learning methods are designed to achieve the segmentation of uterine fibroids. The deep lab model is used to optimize the lesion edge detailed information by using the void convolution algorithm and fully connected CRF, and the two semantic segmentation networks are compared to obtain the best results. The Mask RCNN case segmentation model is used to effectively extract features through the ResNet structure, combined with the RPN network to achieve effective use and fusion of features, and continuously optimize the network training to achieve a fine segmentation of the lesion area, and demonstrate the accuracy and feasibility of the two models in medical image segmentation. Histopathology was used to obtain ER, PR, HER scores, and Ki-67 percentage values for all patients. The Kaplan-Meier method was used for survival estimation, the Log-rank test was used for single-factor analysis, and Cox proportional risk regression was used for multifactor analysis. The prognostic value of each factor was calculated, as well as the factors affecting progression-free survival. This study was done to compare the imaging characteristics and diagnostic value of mammography and colour Doppler ultrasonography in nonspecific mastitis, improve the understanding of the imaging characteristics of nonspecific mastitis in these two examinations, improve the accuracy of the diagnosis of this type of disease, improve the ability of distinguishing it from breast cancer, and reduce the rate of misdiagnosis.

Effects of dietary betaine supplementation on biochemical parameters of blood and testicular oxidative stress in Hu sheep.

Betaine, a highly valuable feed additive, has been observed to alter the distribution of protein and fat in the bodies of ruminants and to exhibit strong antioxidant properties. However, the effects of dietary betaine supplementation on the biochemical parameters of blood and on testicular oxidative stress remain unknown. This study aimed to investigate the effects of dietary betaine supplementation on lipid metabolism, immunity, and testicular oxidative status in Hu sheep. Experimental sheep (n=3, three sheep per group) were fed betaine-containing diets, a basal diet supplemented with 0 g/day (control group), 1 g/day (B1), and 3 g/day betaine (B2). There were no differences in the serum concentrations of triglycerides and cholesterol in Hu sheep receiving diets supplemented with betaine. The ratio of basophils significantly increased in the B1 and B2 groups. ELISA (enzyme-linked immunosorbent assay) results showed that testicular superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity were significantly higher, whereas malondialdehyde (MDA) content significantly decreased, after feeding betaine-supplemented diets. qPCR results showed that the mRNA expression levels of CAT, SOD2, and GSH-Px were significantly upregulated in both the B1 and B2 groups compared to those in the control group. Furthermore, the expression of proliferating cell nuclear antigen (PCNA) was significantly lower in the testes of betaine-treated Hu sheep than in the control group. Moreover, LKB1 (liver kinase B1) expression significantly increased, and mRNA expression of AMPK (AMP-activated serine/threonine protein kinase) significantly decreased in the B1 group. The relative gene expression of mTOR (mechanistic target of rapamycin) was significantly higher in the B2 group than in the control group. RAPTOR expression significantly increased in the B1 group. Western blot revealed that the ratio of P-mTOR and mTOR significantly increased after feeding betaine-supplemented diets. In conclusion, betaine supplementation improved serum lipid metabolism, immune response, and increased the testicular antioxidant capacity of Hu sheep, which might be regulated via mTOR signaling pathway.

ACOX2 is a prognostic marker and impedes the progression of hepatocellular carcinoma via PPARα pathway.

Hepatocellular carcinoma (HCC) has been extensively studied as one of the most aggressive tumors worldwide. However, its mortality rate remains high due to ideal diagnosis and treatment strategies. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient's outcome. In our study, we applied data-independent acquisition (DIA) quantitative proteomics to investigate the expression landscape of 24 paired HCC patients. A total of 1029 differentially expressed proteins (DEPs) were screened. Then, we compared DEPs in our cohort with the differentially expressed genes (DEGs) in The Cancer Genome Atlas, and investigated their prognostic significance, and found 183 prognosis-related genes (PRGs). By conducting protein-protein interaction topological analysis, we identified four subnetworks with prognostic significance. Acyl-CoA oxidase 2 (ACOX2) is a novel gene in subnetwork1, encodes a peroxisomal enzyme, and its function in HCC was investigated in vivo and in vitro. The lower expression of ACOX2 was validated by real-time quantitative PCR, immunohistochemistry, and Western blot. Cell Counting Kit-8 assay, wound healing, and transwell migration assay were applied to evaluate the impact of ACOX2 overexpression on the proliferation and migration abilities in two liver cancer cell lines. ACOX2 overexpression, using a subcutaneous xenograft tumor model, indicated a tumor suppressor role in HCC. To uncover the underlying mechanism, gene set enrichment analysis was conducted, and peroxisome proliferator-activated receptor-α (PPARα) was proposed to be a potential target. In conclusion, we demonstrated a PRG ACOX2, and its overexpression reduced the proliferation and metastasis of liver cancer in vitro and in vivo through PPARα pathway.

Allium Vegetables, Garlic Supplements, and Risk of Cancer: A Systematic Review and Meta-Analysis.

Purpose: The role of allium vegetables or garlic supplements on reducing cancer risk was inconsistent between laboratory study findings and related epidemiologic studies. Methods: Studies assessing the effect of allium vegetables and garlic supplement consumption on cancer risk were included in our meta-analysis. We used fixed- or random-effects models to pool effect measures to evaluate the highest and lowest consumption. A dose-response regression analysis was used to assess the association between allium vegetables, garlic supplements, and cancer risk. Results: In a pooled analysis of 22 studies with 25 reports on allium vegetables, a high consumption of allium vegetables showed no significant association with cancer risk (relative risk [RR] = 0.97, 95% confidence interval [CI] 0.92-1.03) in a fixed-effects model. Similarly, garlic supplements were not found to be significantly associated with an increased risk of cancer (RR = 0.97, 95% CI 0.84-1.12) in a random-effects model involving a pooled analysis of 10 studies with 11 reports. Consumption of allium vegetables did not significantly correspond with cancer risk (P for nonlinearity = 0.958, P for linearity = 0.907). Conclusion: In this meta-analysis, we found no evidence that higher consumption of allium vegetables or garlic supplements reduced the risk of cancer; however, this finding requires further validation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021246947.

Next-Generation Sequencing Characterizes the Landscape of Somatic Mutations and Pathways in Metastatic Bile Tract Carcinoma.

PURPOSE: Tumor metastasis remains the leading cause of cancer-related mortality in biliary tract cancer. The etiology and mechanism of bile tract carcinoma metastasis are unclear. METHODS: The primary tumor and blood samples of 14 patients with biliary tract cancer were collected, followed by nucleic acid extraction and library construction. Target sequencing with 556 panel genes and WES were performed to detect the hot spot genes variations. Bioinformatics was used to comprehensively analyze the sequencing data of these samples, including the differences of tumor mutation burden and signaling pathways. RESULTS: The results showed that the mutation frequency of TP53 gene was the highest and the mutations of CTNNB1, EPHA7, ARID2, and PIK3CA were only found in metastatic samples. The TMB mean values of metastatic and non-metastatic groups were 12.97 and 10.38 mutations per Mb, respectively. There were significant differences in the enrichment pathways of cellular components between the tumor metastasis and non-metastatic samples. CONCLUSIONS: We identified multiple pathway differences, which helps us better understand metastatic biliary tumors and design clinical therapy for personalized medicine.

The role and mechanism of action of RNF186 in colorectal cancer through negative regulation of NF-κB.

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers worldwide. RING finger protein 186 (RNF186) is a member of the RING finger protein family. RNF186 has been reported to be involved in the regulation of the intestinal homeostasis through the regulation of endoplasmic reticulum (ER) stress in colonic epithelial cells. However, its role in CRC remains unclear. In this study, we found that colorectal tumours from human patients had decreased levels of RNF186. We demonstrated that overexpression of RNF186 suppressed the growth and migration of CRC-derived cell lines in vitro and inhibited tumour proliferation in vivo. Further, our findings indicated that forced expression of RNF186 inhibited nuclear factor-κB (NF-κB) activation by reducing the phosphorylation of NF-κB. In addition, our results showed that RNF186-/- mice exhibited significantly increased tumour burden compared to the wild type (WT) mice following treatment with azoxymethane/dextran sulfate sodium (AOM/DSS). Compared to WT mice, the percentage of Ki67 positive cells was increased in the RNF186-/- mice, indicating that RNF186 is crucial for intestinal cell proliferation during tumorigenesis. Taken together, our data suggest that RNF186 inhibits the development of CRC, and that this effect is mediated through the suppression of NF-κB activity.