Decreased Expression of PLD2 Promotes EMT in Colorectal Cancer Invasion and Metastasis.

Background and Objectives: PLD2 has been identified as playing a critical role in cancer cell motility and migration and other pathophysiological processes. We investigated the expression of PLD2 and its biological functions and clinical implications in human colorectal cancer. Materials and Methods: In this study, the expressions of PLD2 were analyzed in CRC cell lines and CRC samples by RT-PCR, western blot and immunohistochemistry. The PLD enzyme activity was studied using an PLD detection kit. We also performed matrigel invasion assay to evaluate the invasive capabilities in CRC cells. The expressions of EMT-related markers were quantified at mRNA and protein level using RT-PCR and western blot. We performed high-throughput RNA sequencing on PLD2 knockdown and overexpression CRC cell lines to explore the changes in gene expression associated with PLD2. Result: Herein, we showed that PLD2 expression was relatively low in CRC cell lines and CRC samples and PLD2 deficiency was significantly correlated with more advanced clinical phenotype regarding lymphatic and distant metastasis and poor patient survival. We also detected that PLD2 knockdown favored epithelial-mesenchymal transition (EMT) and thus promoted CRC invasion and metastasis. Further exploration uncovered that the expressions of several important genes closely related to metabolic pathways in CRC were noticeably altered due to PLD2 deficiency, including ID1, IFIT4, OASL, IFIT2 and CTAG2. Conclusion: Our results revealed that PLD2 deficiency promotes cell invasion and metastasis in CRC via EMT indicating PLD2 might have an important implication in carcinogenesis and progression and would be a new therapeutic target for cancer treatment.

Rigid Fe(III) Chelate with Phosphonate Pendants: A Stable and Effective Extracellular MRI Contrast Agent.

A novel Fe(III) complex, Fe-tBPCDTA, was synthesized and explored as a potential contrast agent for MRI. Compared to established agents like Fe-EDTA and Fe-tCDTA, Fe-tBPCDTA exhibited moderate relaxivity (r1 = 1.17 s-1·mmol-1) due to its enhanced second-sphere mechanism. It also displayed improved kinetic inertness, lower cytotoxicity, and enhanced redox stability. In vivo studies demonstrated its function as an extracellular fluid agent, providing tumor contrast comparable to that of Gd-DTPA at a higher dosage. Complete renal clearance occurred within 24 h. These findings suggest Fe-tBPCDTA as a promising candidate for further development as a safe and effective extracellular MRI contrast agent.

Identification of potential therapeutic targets for breast cancer using Mendelian randomization analysis and drug target prediction.

Breast cancer stands as the foremost cause of cancer-related mortality among women, presenting a substantial economic impact on society. The limitations in current therapeutic options, coupled with poor patient tolerance, underscore the urgent need for novel treatments. Our study embarked on a genomic association exploration of breast cancer, leveraging whole-genome sequencing data from the Finngen database, complemented by expression quantitative trait loci (eQTL) insights from the eQTLGen and GTEx Consortiums. An initial investigation was conducted through summary-based Mendelian randomization (MR) to pinpoint primary eQTLs. Analysis of blood specimens revealed 103 eQTLs significantly correlated with breast cancer. Focusing our efforts, we identified 19 candidates with potential therapeutic significance. Further scrutiny via two-sample MR pinpointed UROD, LMO4, HORMAD1, and ZSWIM5 as promising targets for breast cancer therapy. Our research sheds light on new avenues for the treatment of breast cancer, highlighting the potential of genomic association studies in uncovering viable therapeutic targets.

Association between sleep duration, depression and breast cancer in the United States: a national health and nutrition examination survey analysis 2009-2018.

OBJECTIVE: Breast cancer is the most common cancer in women, threatening both physical and mental health. The epidemiological evidence for association between sleep duration, depression and breast cancer is inconsistent. The aim of this study was to determine the association between them and build machine-learning algorithms to predict breast cancer. METHODS: A total of 1,789 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the study, and 263 breast cancer patients were identified. Sleep duration was collected using a standardized questionnaire, and the Nine-item Patient Health Questionnaire (PHQ-9) was used to assess depression. Logistic regression yielded multivariable-adjusted breast cancer odds ratios (OR) and 95% confidence intervals (CI) for sleep duration and depression. Then, six machine learning algorithms, including AdaBoost, random forest, Boost tree, artificial neural network, limit gradient enhancement and support vector machine, were used to predict the development of breast cancer and find out the best algorithm. RESULTS: Body mass index (BMI), race and smoking were statistically different between breast cancer and non-breast cancer groups. Participants with depression were associated with breast cancer (OR = 1.99, 95%CI: 1.55-3.51). Compared with 7-9h of sleep, the ORs for <7 and >9 h of sleep were 1.25 (95% CI: 0.85-1.37) and 1.05 (95% CI: 0.95-1.15), respectively. The AdaBoost model outperformed other machine learning algorithms and predicted well for breast cancer, with an area under curve (AUC) of 0.84 (95%CI: 0.81-0.87). CONCLUSIONS: No significant association was observed between sleep duration and breast cancer, and participants with depression were associated with an increased risk for breast cancer. This finding provides new clues into the relationship between breast cancer and depression and sleep duration, and provides potential evidence for subsequent studies of pathological mechanisms.

Spleen-dedicated stiffness measurement performed well to rule out high-risk varices in HBV-related hepatocellular carcinoma: Screening for high-risk varices in HCC.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is required to screen for high-risk varices (HRV) in patients with hepatocellular carcinoma (HCC), especially since overall survival rates have dramatically improved with new systemic therapies. AIM: To assess the Baveno VI and Baveno VII algorithms' ability to rule out HRV in hepatitis B virus (HBV)-related HCC METHODS: We prospectively enrolled consecutive patients with HBV related, compensated cirrhosis and newly diagnosed HCC who underwent liver stiffness measurement, spleen stiffness measurement (SSM) using a 100-Hz shear wave frequency, and EGD. RESULTS: From September 2021 to August 2023, we enrolled 219 patients with HCC, with 107 (48.9%) Barcelona Clinic Liver Cancer (BCLC) A, 28 (12.8%) BCLC B and 84 (38.3%) BCLC C, respectively. HRV prevalence was 28.8% (63/219). Baveno VI criteria safely (HRV missing rate, 3.2%) avoided 27.4% unnecessary EGDs, while the Baveno VII algorithm avoided 49.3% with HRV missing rate at 7.9% (5/63). The SSM ≤40 kPa avoided 47.5% of EGDs safely (HRV missing rate, 4.8%), significantly better than the Baveno VI criteria (p < 0.001) and comparable to the Baveno VII algorithm (p = 0.390). The SSM ≤40 kPa safely avoided EGDs in patient subgroups within Milan criteria, with portal vein tumour thrombosis or BCLC B/C or candidates for systemic therapy. CONCLUSIONS: We validated that the SSM ≤40 kPa using a 100-Hz probe could safely eliminate more unnecessary EGDs than the Baveno VI criteria in patients with HBV-related HCC. However, the efficacy of the Baveno VII algorithm in patients with HCC requires further investigation.

Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. Nanosecond pulsed electric fields (nsPEFs) have emerged as a new treatment for cancer. This study aims to identify the effectiveness of nsPEFs in the treatment of HCC and analyze the alterations in the gut microbiome and serum metabonomics after ablation. Methods: C57BL/6 mice were randomly divided into three groups: healthy control mice (n = 10), HCC mice (n = 10), and nsPEF-treated HCC mice (n = 23). Hep1-6 cell lines were used to establish the HCC model in situ. Histopathological staining was performed on tumor tissues. The gut microbiome was analyzed by 16S rRNA sequencing. Serum metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Spearman's correlation analysis was carried out to analyze the correlation between the gut microbiome and serum metabonomics. Results: The fluorescence image showed that nsPEFs were significantly effective. Histopathological staining identified nuclear pyknosis and cell necrosis in the nsPEF group. The expression of CD34, PCNA, and VEGF decreased significantly in the nsPEF group. Compared with normal mice, the gut microbiome diversity of HCC mice was increased. Eight genera including Alistipes and Muribaculaceae were enriched in the HCC group. Inversely, these genera decreased in the nsPEF group. LC-MS analysis confirmed that there were significant differences in serum metabolism among the three groups. Correlation analysis showed crucial relationships between the gut microbiome and serum metabolites that are involved in nsPEF ablation of HCC. Conclusion: As a new minimally invasive treatment for tumor ablation, nsPEFs have an excellent ablation effect. The alterations in the gut microbiome and serum metabolites may participate in the prognosis of HCC ablation.

Combined model with acoustic radiation force impulse to rule out high-risk varices in HBV-related cirrhosis with viral suppression.

AIMS: To prospectively evaluate the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) via acoustic radiation force impulse (ARFI) imaging combined with platelet counts (PLT) in ruling out HRV in HBV-related cirrhotic patients with viral suppression. METHODS: Patients with cirrhosis enrolled between June 2020-March 2022 were divided into a derivation cohort and validation cohort. LSM and SSM ARFI-based, and esophagogastroduodenoscopy (EGD) were performed at enrollment. RESULTS: In the derivation cohort, overall, 236 HBV-related cirrhotic patients with maintained viral suppression were enrolled, and the prevalence of HRV was 19.5% (46/236). With the aim of identifying HRV, the most accurate LSM and SSM cut-offs were chosen of 1.46 m/s and 2.28 m/s, respectively. The combined model (LSM<1.46 m/s and PLT>150 × 109/L strategy combined with SSM ≤ 2.28 m/s) can spare 38.6% of EGDs and 4.3% of HRV cases were misclassified. In the validation cohort, we analysed 323 HBV-related cirrhotic patients with maintained viral suppression and validated the combined model can spare 33.4% (108/323) of EGD, and the HRV missed rate was 3.4%. CONCLUSIONS: A non-invasive prediction model combining LSM<1.46 m/s and PLT>150 × 109/L strategy with SSM ≤ 2.28 m/s exhibited excellent performance in ruling out HRV and avoided a significantly large number (38.6% vs 33.4%) of unnecessary EGDs in HBV-related cirrhotic patients with viral suppression.

The latest research progress on minimally invasive treatments for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail. DATA SOURCES: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords. RESULTS: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC. CONCLUSIONS: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.

MCM4 is a novel prognostic biomarker and promotes cancer cell growth in glioma.

Background: Gliomas account for 75% of all primary malignant brain tumors in adults and result in high mortality. Accumulated evidence has declared the minichromosome maintenance protein complex (MCM) gene family plays a critical role in modulating the cell cycle and DNA replication stress. However, the biological function and clinic characterization of nine MCM members in low-grade glioma are not yet clarified. Methods: In this study, we utilized diverse public databases, including The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt, Human Protein Atlas (HPA), Linkedomics, cbioportal, Tumor and Immune System Interaction Database (TISIDB), single-sample GSEA (ssGSEA), Tumor Immune Estimation Resource (TIMER), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal databases to explore the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, tumor mutational burden (TMB), immune subtype, immune cell infiltration, immune modulator and drug sensitivity of nine MCMs. Afterward, qRT-PCR was utilized to detect the expression of the MCM family in glioblastoma multiforme (GBM) cell lines. The one-, three-, or five-year survival rate was predicted by utilizing a nomogram established by cox proportional hazard regression. Results: In this study, we found that nine MCMs were consistently up-regulated in glioma tissues and glioma cell lines. Elevated nine MCMs expressions were significantly correlated with a higher tumor stage, isocitrate dehydrogenase (IDH) mutates, 1p/19q codeletion, histological type, and primary therapy outcome. Survival analyses showed that higher expression of MCM2-MCM8 (minichromosome maintenance protein2-8) and MCM10 (minichromosome maintenance protein 10) were linked with poor overall survival (OS) and progression-free survival (PFS) in glioma patients. On the other hand, up-regulated MCM2-MCM8 and MCM10 were significantly associated with shorter disease-specific survival (DSS) in glioma patients. Univariate and multivariate analyses revealed that MCM2 (minichromosome maintenance protein2), MCM4 (minichromosome maintenance protein 4), MCM6 (minichromosome maintenance protein 6), MCM7 (minichromosome maintenance protein 7) expression and tumor grade, 1p/19q codeletion, age, and primary therapy outcome were independent factors correlated with the clinical outcome of glioma patients. More importantly, a prognostic MCMs model constructed using the above five prognostic genes could predict the overall survival of glioma patients with medium-to-high accuracy. Furthermore, functional enrichment analysis indicated that MCMs principal participated in regulating cell cycle and DNA replication. DNA copy number variation (CNV) and DNA methylation significantly affect the expression of MCMs. Finally, we uncover that MCMs expression is highly correlated with immune cell infiltration, immune modulator, TMB, and drug sensitivity. Conclusions: In summary, this finding confirmed that MCM4 is a potential target of precision therapy for patients with glioma.

Exploration of hub genes, lipid metabolism, and the immune microenvironment in stomach carcinoma and cholangiocarcinoma.

Background: Gastric cancer (GC) is the 5th most common cause of cancer in the world and the 3rd largest cause of cancer-related death. It is usually associated with a variety of cancers, of which cholangiocarcinoma (CCA) combined with GC accounts for about 1.6%. This study sought to examine the hub genes and role of lipid metabolism in the development and diagnosis of GC and CCA. Methods: To screen potential hub genes, The Cancer Genome Atlas (TCGA) data sets, including the GC (STAD, dataset of GC) and CCA (CHOL, dataset of CCA) data sets, were used to conduct a differentially expressed gene (DEG) analysis and an enrichment analysis of the DEGs. A weighted-gene co-expression network analysis (WGCNA) was conducted to identify the significant gene module and then find the hub genes in the module. To verify the 4 hub genes, we conducted a differentiation analysis of the 4 genes in GC and CCA and found that there were differences. A survival analysis of the hub genes was performed and mutations were mapped. Additionally, tumor immune microenvironment (TIME) and immune analyses were performed to evaluate how lipid metabolism affects the development of GC with CCA. Results: The principal component analysis showed that both GC and CCA had distinct up-regulated and down-regulated genes, which are involved in a variety of metabolic processes. Upon WGCNA, the turquoise and blue modules were meaningful, and the hub genes were identified from these 2 modules. Four hub genes were identified: amyloid beta precursor protein binding family B member 1 (APBB1), Homo sapiens armadillo repeat containing X-linked 1 (ARMCX1), DAZ interacting zinc finger protein 1 (DZIP1), and methionine sulfoxide reductase B3 (MSRB3). In survival analysis, increased expression of the 4 hub genes was associated with inferior survival outcomes, with variations in all 4 genes. Additionally, we demonstrated that genes related to lipid metabolism had an effect on immune function. Conclusions: APBB1, ARMCX1, DZIP1, and MSRB3 affect the development of GC and CCA and can be used as biomarkers. The expression of lipid metabolism genes is related to the TIME of patients with GC and CCA.

Migration and Removal of Labile Cadmium Contaminants in Paddy Soils by Electrokinetic Remediation without Changing Soil pH.

Electrokinetic remediation (EKR) is a viable, advanced cleaning strategy that can permanently reduce the toxicity of soil contaminants. However, EKR is prone to causing changes in soil pH. The negative impacts must be minimized if field-scale application is to be realized. In this study, EKR with polarity reversal was used to avoid soil pH polarization and to clean up cadmium (Cd)-contaminated paddy soils. Results showed that Cd desorbed from oxidizable and residual fractions to labile and easily available parts. Soil moisture content above 0.35 g g-1 was conductive to achieving the desirable Cd-migration rate. The exchangeable Cd phase eventually migrated from both ends of that soil compartment towards the intermediate. Moreover, the addition of citric acid at the concentration of 0.1 mol L-1 was an effective enhancement strategy. The methodology enriched Cd contaminants to specific sites. The technology can be used for electrokinetic-assisted phytoremediation during the rice growing period. Hyperaccumulator is planted in the intermediate area to remove the Cd contaminants. On the other hand, Cd removal is achieved in the region close to the electrodes. The present study provides a theoretical basis for in situ remediation. It has a wider significance for field-scale application.

Rapid and automatic assessment of early gestational age using computer vision and biometric measurements based on ultrasound video.

Background: Early gestational age (GA) assessment using ultrasound is a routine and frequent examination performed in hospitals whereby clinicians manually measure the size of the gestational sac using ultrasound and calculate GA. However, the error is often substantial, and the process is laborious. To overcome these challenges, we propose a new system to assess early GA using a new end-to-end computer vision system and a new biometric measurement method based on ultrasound video. Methods: In this retrospective study, a new system was provided. B-ultrasound videos were first decomposed into two-dimensional (2D) images, and the contours of the gestational sac were extracted and drawn. The maximum length and short diameter of the gestational sac were then automatically measured and GA was calculated using the Hellman formula. Finally, through human-machine comparison, the clinicians' assessment errors were analyzed by SPSS 26. Results: In this study, 29,829 2D images of 191 B-ultrasound videos were evaluated using the new system. Clinicians usually require 15-20 min to complete assessments of GA, whereas with the new system assessments can be completed in approximately 30 s. Moreover, a human-machine comparison showed that the system helped intermediate skills clinicians improve their relative diagnostic error by 13.45% with an absolute error of 7 days. In addition, the new system was used to identify other lesions in the uterus and measure their size as a "sanity check". Conclusions: The proposed new system is a practical, reproducible, and reliable approach for assessing early GA.

Feasibility analysis of CT-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy.

Purpose: To analyze the safety and feasibility of computed tomography (CT)-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy. Methods: The data of 431 patients with 540 lung nodules undergoing CT-guided biopsy or ablation were retrospectively analyzed. Biopsy-only group (A): 107 patients (107 lesions) received CT-guided percutaneous lung biopsy only; Ablation-only group (B): 117 cases (117 lesions) only received CT-guided thermal ablation; Single focal ablation combined with biopsy group (C): 103 patients (103 lesions) received CT-guided thermal ablation combined with intraoperative immediate biopsy; Multifocal ablation combined with biopsy group (D): 104 patients (213 lesions) received CT-guided thermal ablation combined with intraoperative biopsy. The success rate of this technique was calculated, the complications were recorded, and the positive rate of pathological diagnosis of the specimens was evaluated (the tissue specimens could be confirmed as positive by pathological diagnosis). Results: All 431 patients with pulmonary nodules successfully completed the operation, and the technical success rate was 100% (431/431). In group A, hemoptysis occurred in seven cases after operation, while no hemoptysis was observed in the other groups. Pneumothorax occurred in 8 cases in group A, 14 cases in group B, 11 cases in group C, and 13 cases in group D. Hydrothorax occurred in 4 cases in group A, 7 cases in group B, 5 cases in group C and 9 cases in group D, and there were no significant differences between the groups. The positive rate of pathological diagnosis was 84.1% (90/107) in group A, 81.5% (84/103) in group C, and 82.6% (176/213) in group D, and there was no significant difference among the groups (P > 0.05). A total of 15 cases in group C and 23 cases in group D underwent gene testing and analysis, and the biopsy tissue samples all met quality control standards. Conclusion: CT-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy does not prolong the length of hospital stay or increase the risk of postoperative complications. It can meet the requirements of clinical, pathological and genetic testing, and is safe and reliable.

Dysbiosis in the Human Microbiome of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the most common malignant tumor of the biliary system with a very poor prognosis. The human microbiome, which is the sum of the genetic information of human microorganisms, plays an important role in regulating the digestion, absorption, immune response, and metabolism of the host. Increasing evidence indicates a close relationship between CCA and the human microbiome. Specific alterations occur in the human microbiome of patients with CCA. Therefore, in this review, we aimed to summarize the recent evidence on dysbiosis in the human microbiome of CCA. Then, we generalized the effect of Helicobacter pylori on CCA. Additionally, the potential mechanism of human microbial dysbiosis promoted the progress of CCA, and its precancerous disease was also explored. Furthermore, the possibility of the human microbiome as a diagnostic and therapeutic target of CCA was discussed.

Phosphorylation of Dynamin-Related Protein 1 (DRP1) Regulates Mitochondrial Dynamics and Skeletal Muscle Wasting in Cancer Cachexia.

BACKGROUND: Cancer-associated cachexia (CAC) is a syndrome characterized by skeletal muscle atrophy, and the underlying mechanisms are still unclear. Recent research studies have shed light on a noteworthy link between mitochondrial dynamics and muscle physiology. In the present study, we investigate the role of dynamin-related protein 1 (DRP1), a pivotal factor of mitochondrial dynamics, in myotube atrophy during cancer-associated cachexia. METHODS: Seventy-six surgical patients, including gastrointestinal tumor and benign disease, were enrolled in the study and divided to three groups: control, non-cachexia, and cancer-associated cachexia. Demographic data were collected. Their rectus abdominis samples were acquired intraoperatively. Muscle fiber size, markers of ubiquitin proteasome system (UPS), mitochondrial ultrastructure, and markers of mitochondrial function and dynamics were assayed. A cachexia model in vitro was established via coculturing a C2C12 myotube with media from C26 colon cancer cells. A specific DRP1 inhibitor, Mdivi-1, and a lentivirus of DRP1 knockdown/overexpression were used to regulate the expression of DRP1. Muscle diameter, mitochondrial morphology, mass, reactive oxygen species (ROS), membrane potential, and markers of UPS, mitochondrial function, and dynamics were determined. RESULTS: Patients of cachexia suffered from a conspicuous worsened nutrition status and muscle loss compared to patients of other groups. Severe mitochondrial swelling and enlarged area were observed, and partial alterations in mitochondrial function were found in muscle. Analysis of mitochondrial dynamics indicated an upregulation of phosphorylated DRP1 at the ser616 site. In vitro, cancer media resulted in the atrophy of myotube. This was accompanied with a prominent unbalance of mitochondrial dynamics, as well as enhanced mitochondrial ROS and decreased mitochondrial function and membrane potential. However, certain concentrations of Mdivi-1 and DRP1 knockdown rebalanced the mitochondrial dynamics, mitigating this negative phenotype caused by cachexia. Moreover, overexpression of DRP1 aggravated these phenomena. CONCLUSION: In clinical patients, cachexia induces abnormal mitochondrial changes and possible fission activation for the atrophied muscle. Our cachexia model in vitro further demonstrates that unbalanced mitochondrial dynamics contributes to this atrophy and mitochondrial impairment, and rebuilding the balance by regulating of DRP1 could ameliorate these alterations.

RPL19 Is a Prognostic Biomarker and Promotes Tumor Progression in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies, and the therapeutic outcome remains undesirable due to its recurrence and metastasis. Gene dysregulation plays a pivotal role in the occurrence and progression of cancer, and the molecular mechanisms are largely unknown. METHODS: The differentially expressed genes of HCC screened from the GSE39791 dataset were used to conduct weighted gene co-expression network analysis. The selected hub genes were validated in The Cancer Genome Atlas (TCGA) database and 11 HCC datasets from the Gene Expression Omnibus (GEO) database. Then, a tissue microarray comprising 90 HCC specimens and 90 adjacent normal specimens was used to validate the hub genes. Moreover, the Hallmark, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify enriched pathways. Then, we conducted the immune infiltration analysis. RESULTS: A total of 17 co-expression modules were obtained by weighted gene co-expression network analysis. The green, blue, and purple modules were the most relevant to HCC samples. Four hub genes, RPL19, RPL35A, RPL27A, and RPS12, were identified. Interestingly, we found that all four genes were highly expressed in HCC and that their high expression was related to a poor prognosis by analyzing the TCGA and GEO databases. Furthermore, we investigated RPL19 in HCC tissue microarrays and demonstrated that RPL19 was overexpressed in tumor tissues compared with non-tumor tissues (p = 0.016). Moreover, overexpression of RPL19 predicted a poor prognosis in hepatocellular carcinoma (p < 0.0007). Then, enrichment analysis revealed that cell cycle pathways were significantly enriched, and bile acid metabolism-related pathways were significantly down-regulated when RPL19 was highly expressed. Furthermore, immune infiltration analysis showed that immune response was suppressed. CONCLUSION: Our study demonstrates that RPL19 may play an important role in promoting tumor progression and is correlated with a poor prognosis in HCC. RPL19 may serve as a promising biomarker and therapeutic target for the precise diagnosis and treatment of HCC in the future.

Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota.

Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.

Prenatal diagnosis and postnatal management of congenital mesoblastic nephroma: Experience at a single center in China.

OBJECTIVE: To review the prenatal and postnatal clinical characteristics and pathological subtypes, as well as the surgical outcome for congenital mesoblastic nephroma (CMN) cases. METHOD: A retrospective review was performed in 11 cases with CMN prenatally diagnosed at a single center between 2015 and 2019. The clinical characteristics, surgical outcome, histopathology, and follow-up were retrospectively obtained and reviewed. RESULTS: The median gestational age at which the sonographic diagnosis was made was 35 weeks. Polyhydramnios was found in four (36.4%) cases, and all resulted in a preterm birth. Nine infants had hypertension. Ten cases underwent radical nephrectomy, and one underwent radical nephrectomy and partial adrenalectomy. The pathological results showed that six tumors were classical variants, four mixed variants, and one was a cellular variant. Three cases presented as a stage I, eight as stage II, and no stage III or IV cases were diagnosed. All patients are alive so far. At a median follow-up of 14 months, no local recurrence, or remote metastases were found. CONCLUSION: The prognosis of prenatal CMN cases is excellent after early surgery.