Association of redundant foreskin with sexual dysfunction: a cross-sectional study from 5700 participants.

A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China). Clinical characteristics, including foreskin length, were collected, and sexual function was assessed by the International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires. Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction. Among the 2721 erectile dysfunction (ED) patients and 1064 premature ejaculation (PE) patients, 301 (11.1%) ED patients and 135 (12.7%) PE patients had redundant foreskin, respectively. Men in the PE group were more likely to have redundant foreskin than men in the non-PE group (P = 0.004). Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED (adjusted odds ratio [aOR] = 1.31, adjusted P = 0.04), moderate PE (aOR = 1.38, adjusted P = 0.02), and probable PE (aOR = 1.37, adjusted P = 0.03) after adjusting for confounding variables. Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction, especially in PE patients. Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.

Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview.

Drug-induced liver injury is a prevalent severe adverse event in clinical settings, leading to increased medical burdens for patients and presenting challenges for the development and commercialization of novel pharmaceuticals. Research has revealed a close association between gut microbiota and drug-induced liver injury in recent years. However, there has yet to be a consensus on the specific mechanism by which gut microbiota is involved in drug-induced liver injury. Gut microbiota may contribute to drug-induced liver injury by increasing intestinal permeability, disrupting intestinal metabolite homeostasis, and promoting inflammation and oxidative stress. Alterations in gut microbiota were found in drug-induced liver injury caused by antibiotics, psychotropic drugs, acetaminophen, antituberculosis drugs, and antithyroid drugs. Specific gut microbiota and their abundance are associated closely with the severity of drug-induced liver injury. Therefore, gut microbiota is expected to be a new target for the treatment of drug-induced liver injury. This review focuses on the association of gut microbiota with common hepatotoxic drugs and the potential mechanisms by which gut microbiota may contribute to the pathogenesis of drug-induced liver injury, providing a more comprehensive reference for the interaction between drug-induced liver injury and gut microbiota.

Radiomics features based on dual-area CT predict the expression levels of fatty acid binding protein 4 and outcome in hepatocellular carcinoma.

RATIONALE AND OBJECTIVES: To evaluate the predictive value of tumor and peritumor radiomics in the fatty acid binding protein 4 (FABP4) expression levels and overall survival in patients with hepatocellular carcinoma. MATERIALS AND METHODS: The genomic data of HCC patients were obtained from The Cancer Genome Atlas. The Dual-area CT images of corresponding patients were downloaded from The Cancer Imaging Archive, for radiomics feature extraction, model construction and prognosis analysis. Simultaneously, using patients from Sichuan Provincial People's Hospital, the prognostic value of the radiomics model in HCC patients was validated. RESULTS: In the TCIA database, the area under the curve (AUC) values of the volumes of interest (VOI)whole model in the training set and internal validation set were 0.812 and 0.754, respectively, and the AUC value of VOIwhole+periphery in the training set and internal validation set were 0.866 and 0.779, respectively. In the VOIwhole and the VOIwhole+periphery model of the independent cohort, there were significant differences in OS between the high and low rad-score groups (P = 0.009, P = 0.021, respectively). Significant positive correlations can be observed between FABP4 expression and correlations with rad-score of VOIwhole model (r = 0.691) and VOIwhole+periphery model (r = 0.732) in the independent cohort. CONCLUSION: Radiomics models of tumor and peritumor Dual-area CT images could predict stably the expression levels of FABP4 and may be helping in personalized treatment strategies.

Allograft function predicts mortality in kidney transplant recipients with severe COVID-19: a paradoxical risk factor.

Introduction: Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs. Methods: This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results. Results: The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], P=0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, P=0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, P=0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, P=0.018) was a protective factor against death in severe COVID-19. Conclusions: Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.

High ANO1 expression is a prognostic factor and correlated with an immunosuppressive tumor microenvironment in pancreatic cancer.

Background: Aminooctylamine (ANO1) plays an oncogenic role in various cancers. However. its role in pancreatic cancer (PC) has rarely been studied. This study investigated the prognostic value of ANO1 and its correlation with the tumor microenvironment (TME) in PC. Methods: Consecutive patients with PC (n = 119) were enrolled. The expression of ANO1 in cancer cells, the expression of fibroblast activation protein (FAP) and alpha smooth muscle actin in cancer-associated fibroblasts (CAFs), and the numbers of CD8- and FOXP3-positive tumor-infiltrating lymphocytes (TILs) were evaluated using immunohistochemistry. The prognostic value of ANO1 and its correlation with CAF subgroups and TILs were analyzed. The possible mechanism of ANO1 in the TME of PC was predicted using the the Cancer Genome Atlas (TCGA) dataset. Results: The expression of AN01 was correlated with overall survival (OS) and disease-free survival. Multi-factor analysis showed that high ANO1 expression was an independent adverse prognostic factor for OS (hazard ratio, 4.137; P = 0.001). ANO1 expression was positively correlated with the expression of FAP in CAFs (P < 0.001) and negatively correlated with the number of CD8-positive TILs (P = 0.005), which was also validated by bioinformatics analysis in the TCGA dataset. Moreover, bioinformatic analysis of the TCGA dataset revealed that ANO1 may induce an immunosuppressive tumor microenvironment in pancreatic cancer in a paracrine manner. Conclusion: ANO1 is a prognostic factor in patients with PC after radical resection. ANO1 may induce an immunosuppressive tumor microenvironment in PC in a paracrine manner, suggesting that ANO1 may be a novel therapeutic target.

Effect of leukocytes on semen quality in men from primary and secondary infertile couples: A cross-sectional study.

Background and Aims: Leukocytospermia (LCS) is a known cause of male infertility. However, the relationship between seminal leukocytes and semen quality among infertile couples remains controversial. This study aims to investigate the association between semen quality and LCS in male partners of infertile couples. Methods: Semen samples were collected from 512 men who asked for a fertility evaluation in a reproductive center in China. Seminal leukocytes were counted following peroxidase staining with benzidine. Other semen parameters were compared in subfertile men with and without LCS. Results: Poor semen quality (e.g., low semen volume, sperm concentration, and sperm progressive/total motility) was observed among men with LCS compared to those without LCS. Men with LCS had a higher risk of low sperm progressive motility (OR = 0.99, 95% CI = 0.98-0.99, p = 0.02) and total motility (OR = 0.99, 95% CI = 0.98-0.99, p = 0.02), even after adjustment for potential confounders (both OR = 0.99, 95% CI = 0.98-0.99, p = 0.03). Lower sperm viability was observed in LCS from male partners of secondary couples, while no significant difference in semen parameters was found between men with and without LCS in male partners of primary infertile couples. Low sperm motility and viability were associated with LCS in men from secondary infertile couples after adjusting for confounders (OR = 0.97, 95% CI = 0.95-0.99, p = 0.04; OR = 0.94, 95% CI = 0.89-0.99, p = 0.04, respectively). Conclusions: Our findings indicate that a higher risk of abnormal semen parameters was correlated with an increased number of leukocytes in men from secondary infertile couples.

Unraveling the photochemical reactivity of dissolved organic matter in the Yangtze river estuary: Integrating incubations with field observations.

Dissolved organic matter (DOM) sustains a substantial part of the organic matter transported seaward in large estuaries, where photochemical reactions significantly influence its transformation and fate. Irradiation experiments can provide valuable information on the photochemical reactivity (photo-labile, photo-resistant, and photo-product) of molecules. However, previous research paid less attention to exploring the controls of the initial DOM chemistry to irradiation experiments and examining the applicability of their further integration with field research. Here, we conducted irradiation experiments for samples from the freshwater and seawater endmember of the Yangtze River Estuary (YRE), which receives organic matter transport from the largest river in China, the Yangtze River. Molecules that occurred before and after irradiation experiments were characterized by the Fourier transform ion cyclotron resonance mass spectrometry. Results show that both post-irradiation samples have the lower aromaticity degree and reduced oxidation state, while the freshwater endmember sample exhibits more dramatic changes, indicating the controls of parent molecules to the effect of irradiation experiments. Integrating with the "molecular matching" approach, we compared the molecules occurring in field samples with the classified molecules (photo-resistant, photo-labile, and photo-product) acquired from performed irradiation experiments and correlated the relative intensity of photochemical reactivity types with salinity. When applying results from different experiments to conduct "molecular matching", the photo-resistant and photo-labile relative intensity possess consistently positive and negative trends with increasing salinity, respectively. This suggests their reliability for molecular matching applications, while the inconsistent trends for the photo-product relative intensity with salinity suggest its uncertainty in assessing the photo-induced effects. Moreover, the molecular composition within the photochemical reactivity types in field samples also evolved along the salinity gradient and showed similar trends with the DOM changes after experimental irradiation. Despite various factors influencing estimations, it is revealed that a fraction of aromatic molecules and majority of carboxyl-rich alicyclic molecules considered with biologically persistent nature in the YRE freshwater zone are simultaneously not susceptible to photochemical transformation to potentially constitute a long-term marine carbon sink. This study emphasizes the importance and limitations of the combination of field research and laboratory-controlled experiments to provide a better understanding of the crucial role of photochemical reactions in affecting carbon cycling in large estuaries.

The gut microbiome and metabolome in kidney transplant recipients with normal and moderately decreased kidney function.

BACKGROUND: The kidney transplant recipients (KTRs) were diagnosed with Chronic Kidney Disease after transplantation (CKD-T). CKD-T can be affected by the microbial composition and metabolites. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of CKD-T. METHODS: We collected 100 fecal samples of KTRs and divided them into two groups according to the stage progression of CKD-T. Among them, 55 samples were analyzed by Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of KTRs were comprehensively characterized. RESULTS: As well as significant differences in gut microbiome diversity between the CKD G1-2T group and CKD G3T group. Eight flora including Akkermansia were found to be enriched in CKD G3T group. As compared with CKD G1-2T group, the relative abundance of some amino acid metabolism, glycerophospholipid metabolism, amino acid biosynthesis, carbohydrate metabolism and purine metabolism in CKD G3T group were differential expressed significantly. In addition, fecal metabolome analysis indicated that CKD G3T group had a unique metabolite distribution characteristic. Two differentially expressed metabolites, N-acetylornithine and 5-deoxy-5'-(Methylthio) Adenosine, were highly correlated with serum creatinine, eGFR and cystatin C. The enrichment of gut microbial function in CKD-T is correlated with the expression of gut metabolites. CONCLUSION: Gut microbiome and metabolites in the progression of CKD-T display some unique distribution and expression characteristics. The composition of the gut microbiome and their metabolites appears to be different between patients with CKD G3T and those with CKD G1-2T.

Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.

OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM. METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized. RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites. CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.

Quantification of Postoperative Graft-Derived Cell-Free DNA to Evaluate the Risks of Impaired Allograft Function at Early Stage of Kidney Transplantation.

BACKGROUND: Graft-derived cell-free DNA (GcfDNA) is a promising biomarker for comprehensive monitoring of allograft injury because it overcomes the limitations of traditional approaches. The aim of this study is to investigate the association between the outliers of GcfDNA at initial time post transplantation and short-term renal graft function. METHODS: A total of 230 recipients who underwent primary kidney transplantation were recruited in the study. For each recipient, 10 mL of peripheral blood were collected at day 1 post transplantation. Both of the GcfDNA fraction (%) and GcfDNA concentration (cp/mL) were determined using droplet digital PCR. The study was conducted in accordance with the 1964 Helsinki Declaration and its later amendments. RESULTS: There were no values that fall outside of the lower extreme in both of the GcfDNA fraction and GcfDNA concentration, and the upper fence of GcfDNA fraction and GcfDNA concentration were 13.5% and 680 cp/mL, respectively. Recipients with GcfDNA concentration ≥680 cp/mL had a statistically significant higher serum creatinine at day 7 post-transplantation, when compared with the other group (P = .008). The receiver operating characteristic analysis obtained an area under the curve value of 0.869 when using GcfDNA concentration to predict the risk of serum creatinine ≥400 µmol/L, an optimal cut-off value was indicated at 975 cp/mL with high sensitivity (87.5%) and specificity (85%). CONCLUSION: Our results suggest that the quantification of GcfDNA at initial time after transplantation might be used as a novel strategy for predicting short-term risk of impaired kidney allograft function or delayed graft function.

Detection of BK polyomavirus-associated nephropathy using plasma graft-derived cell-free DNA: Development of a novel algorithm from programmed monitoring.

Graft-derived cell-free DNA (GcfDNA) is a promising non-invasive biomarker for detecting allograft injury. In this study, we aimed to evaluate the efficacy of programmed monitoring of GcfDNA for identifying BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients. We recruited 158 kidney transplant recipients between November 2020 and December 2021. Plasma GcfDNA was collected on the tenth day, first month, third month, and sixth month for programmed monitoring and one day before biopsy. ΔGcfDNA (cp/mL) was obtained by subtracting the baseline GcfDNA (cp/mL) from GcfDNA (cp/mL) of the latest programmed monitoring before biopsy. The receiver operating characteristic curve showed the diagnostic performance of GcfDNA (cp/mL) at biopsy time and an optimal area under the curve (AUC) of 0.68 in distinguishing pathologically proven BKPyVAN from pathologically unconfirmed BKPyVAN. In contrast, ΔGcfDNA (cp/mL) had a sensitivity and specificity of 80% and 84.6%, respectively, and an AUC of 0.83. When distinguishing clinically diagnosed BKPyVAN from clinical excluded BKPyVAN, the AUC of GcfDNA (cp/mL) was 0.59 at biopsy time, and ΔGcfDNA (cp/mL) had a sensitivity and specificity of 81.0% and 76.5%, respectively, and an AUC of 0.81. Plasma ΔGcfDNA (cp/mL) was not significantly different between TCMR [0.15 (0.08, 0.24) cp/mL] and pathologically proven BKPyVAN[0.34 (0.20, 0.49) cp/mL]. In conclusion, we recommend programmed monitoring of plasma GcfDNA levels after a kidney transplant. Based on our findings from the programmed monitoring, we have developed a novel algorithm that shows promising results in identifying and predicting BKPyVAN.

Whole Genome Profiling of Lung Microbiome in Solid Organ Transplant Recipients Reveals Virus Involved Microecology May Worsen Prognosis.

Solid organ transplantation (SOT) is the final therapeutic option for recipients with end-stage organ failure, and its long-term success is limited by infections and chronic allograft dysfunction. Viral infection in SOT recipients is considered an important factor affecting prognosis. In this study, we retrospectively analyzed 43 cases of respiratory infections in SOT recipients using metagenomic next-generation sequencing (mNGS) for bronchoalveolar lavage fluid (BALF). At least one virus was detected in 26 (60.5%) recipients, while 17 (39.5%) were virus-negative. Among virus-positive recipients, cytomegalovirus (CMV) was detected in 14 (32.6%), Torque teno virus (TTV) was detected in 9 (20.9%), and other viruses were detected in 6 (14.0%). Prognostic analysis showed that the mortality of the virus-positive group was higher than that of the virus-negative group regardless whether it is the main cause of infection. Analysis of different types of viruses showed that the mortality of the CMV-positive group was significantly higher than that of the CMV-negative group, but no significant difference was observed in other type of virus groups. The diversity analysis of the lung microbiome showed that there was a significant difference between the virus-positive group and the negative group, in particular, the significant differences in microorganisms such as Pneumocystis jirovecii (PJP) and Moraxella osloensiswere detected. Moreover, in the presence of CMV, Pneumocystis jirovecii, Veillonella parvula, and other species showed dramatic changes in the lung of SOT patients, implying that high degree of co-infection between CMV and Pneumocystis jirovecii may occur. Taken together, our study shows that the presence of virus is associated with worse prognosis and dramatically altered lung microbiota in SOT recipients.

Use of graft-derived cell-free DNA as a novel biomarker to predict allograft function after kidney transplantation.

OBJECTIVE: To investigate the association between graft-derived cell-free DNA and pretransplantation clinical variables, and to determine whether the former could be used as a novel biomarker to predict renal function. METHODS: A total of 87 recipients who underwent primary kidney transplantation were recruited to the study. For each recipient, 10 mL peripheral blood was collected on days 1, 7, 14-20, and 30-45 after transplantation. The fractional abundance of graft-derived cell-free DNA was determined using droplet digital polymerase chain reaction. RESULTS: For most recipients, graft-derived cell-free DNA fraction values were significantly elevated on the first day after transplantation, followed by a rapid decline, and reaching baseline values of graft-derived cell-free DNA fraction in the range of <1% at 7 days. Statistical analysis showed that longer cold ischemia time was significantly associated with higher graft-derived cell-free DNA fraction values (P = 0.02). Moreover, we also found that graft-derived cell-free DNA fraction values among recipients with delayed graft function were significantly higher than those of recipients without delayed graft function on the first day after transplantation. Kaplan-Meier analysis showed that recipients who had a graft-derived cell-free DNA fraction value of <1% at 7 days had a significantly lower probability of an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 at 90 days. Using a random forest regression model, the predicted values of estimated glomerular filtration rate at 90 days were almost the same as the actual values. CONCLUSIONS: Our findings suggest that graft-derived cell-free DNA might be used as a novel biomarker to predict delayed graft function and renal function.

Survival and Complication of Liver Transplantation in Infants: A Systematic Review and Meta-Analysis.

Background: Modern surgical techniques and scientific advancements have made liver transplant (LT) in infants feasible. However, there are only a small number of studies examining the short- as well as long-term outcomes of LT in this vulnerable subset of children. Methods: Comprehensive searches were done systematically through the PubMed, Scopus, and Google scholar databases. Studies that were retrospective record based or adopted a cohort approach and reported either patient survival rates or graft survival rates or complications of LT in infants were included in the meta-analysis. Statistical analysis was done using STATA version 13.0. Results: A total of 22 studies were included in the meta-analysis. The overall pooled patient survival rate at 1 year, >1-5 years, and >5 years post-transplantation was 85% (95% CI: 78--92%), 71% (95% CI: 59-83%), and 80% (95% CI: 69-91%), respectively. The overall pooled graft survival rate at 1 year, >1-5 years, and >5 years post-transplantation was 72% (95% CI: 68-76%), 62% (95% CI: 46-78%), and 71% (95% CI: 56-86%), respectively. The overall pooled rate for vascular complications, need for re-transplantation, biliary complications, and infection/sepsis was 12% (95% CI: 10-15%), 16% (95% CI: 12-20%), 15% (95% CI: 9-21%), and 50% (95% CI: 38-61%), respectively. Conclusion: The current meta-analysis showed modest patient and graft survival rates for infant liver transplantation. However, the complication rates related to infection/sepsis were high. More comprehensive evidence is required from studies with larger sample sizes and a longer duration of follow-up.

LncRNA SNHG6 promotes G1/S-phase transition in hepatocellular carcinoma by impairing miR-204-5p-mediated inhibition of E2F1.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) function as competitive endogenous RNA (ceRNA) targeting proteins and genes; however, the role of lncRNAs in hepatocellular carcinoma (HCC) is not well understood. We investigated the mechanism by which lncRNA SNHG6 promotes the development of HCC. RT-qPCR revealed upregulated lncRNA SNHG6 in the HCC setting. Elevated SNHG6 expression was indicative of poor prognosis in patients with HCC. SNHG6 overexpression resulted in increased cyclin D1, cyclin E1, and E2F1 expression both in vitro and in vivo. SNHG6 also promoted HCC cell proliferation by enhancing G1-S phase transition in vitro. Dual luciferase reporter assays, RIP, and RNA pull-down assays demonstrated SNHG6 competitively bound to miR-204-5p and inhibited its expression preventing miR-204-5p from targeting E2F1. Overexpression of miR-204-5p abolished the effect of SNHG6. Our data suggest that SNHG6 functions as a ceRNA that targets miR-204-5p resulting in an increased E2F1 expression and enhanced G1-S phase transition, thereby promoting the tumorigenesis of HCC.

LINC01419-mediated epigenetic silencing of ZIC1 promotes metastasis in hepatocellular carcinoma through the PI3K/Akt signaling pathway.

Hepatocellular carcinoma (HCC) is a rapidly growing tumor characterized by a high potential for vascular invasion and metastasis. The purpose of our study is to explore the regulation mechanism of long noncoding RNA (lncRNA) LINC01419 on cell-cycle distribution and metastasis in hepatocellular carcinoma (HCC) by regulating zinc finger of the cerebellum (ZIC1) through PI3K/Akt signaling pathway. Bioinformatics analysis and dual-luciferase reporter assay were used to analyze LINC01419 and related genes in HCC, and their expression in HCC tissues and adjacent normal tissues were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Then, HCC cell lines were subjected to the construction of LINC01419/ZIC1 overexpression/knockdown cells utilizing lentiviral vectors. RIP and ChIP assays were applied to identify the LINC01419-binding protein. BSP and MSP assays were used to determine gene methylation. According to the results, LINC01419 was highly expressed in HCC tissues and cells, while ZIC1 was poorly expressed. LINC01419 targeted and downregulated ZIC1 expression. Furthermore, LINC01419 increased the methylation of ZIC1 promoter and repressed ZIC1 expression. PI3K/Akt signaling pathway was activated by LINC01419 overexpression and ZIC1 knockdown, under which conditions, the HCC cell self-renewal and proliferation were promoted while cell apoptosis was attenuated, accompanied by accelerated formation and metastasis of xenografted tumors in mice. In conclusion, LINC01419 enhances the methylation of ZIC1 promoter, inhibits ZIC1 expression, and activates the PI3K/Akt signaling pathway, thereby enhancing the malignant phenotypes of HCC cells in vitro as well as tumor formation and metastasis in vivo.

Serum Procalcitonin Correlates With Renal Function and Immune Components in Early-Stage Renal Transplant Recipients.

BACKGROUND: In renal transplantation, monitoring procalcitonin (PCT) in the early post-transplant period can be a promising method for early tracking of infectious complications. However, the correlation between PCT and infection-related factors and immune components and renal function remains unclear. PATIENTS AND METHODS: Between November 2017 and December 2018, 62 early-stage renal transplant recipients were selected, and 4 mL peripheral blood samples were collected to detect the changes of specific immune cells and cytokines. Our study was in compliance with the Helsinki Congress and the Declaration of Istanbul; no prisoners were used, and participants were neither paid nor coerced in our study. RESULTS: According to serum PCT levels, recipients were divided into a high group (PCT ≥ 0.5 ng/mL) and a low group (PCT < 0.5 ng/mL). Compared with the low group, creatinine, cystatin C, urea, T helper type (Th) 22 cells, IL-22 + Th17 cells, interleukin (IL)-22, tumor necrosis factor alpha, and IL-17A increased while estimated glomerular filtration rate (eGFR) was decreased in the high group. In addition, PCT was significantly correlated with eGFR in the high group. CONCLUSIONS: Serum PCT is related with renal function and seems to be associated with immune components in early-stage renal transplant recipients.

Comprehensive analysis of prognostic value and immune infiltration of calpains in pancreatic cancer.

BACKGROUND: Calpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases involved in cancer initiation, progression, and metastasis. However, its role in pancreatic cancer (PC) is still unclear. This study aims to identify the prognostic value and immune infiltration of CAPNs for PC patients using comprehensive bioinformatics analyzes. METHODS: We analyzed the transcription levels of CAPNs in different cancers from Oncomine, differential gene expression in tumor/normal tissues and pathological stage through GEPIA database, the prognostic value of the mRNA expression of CAPNs by Kaplan-Meier plotter, the protein expression comparison of different CAPNs in human tumor/normal tissues from The Human Protein Atla, the CAPNs gene alterations through cBioPortal, the prediction of protein-protein interactions by STRING and GeneMANIA, the functional enrichment of discrepant CAPNs by GO and KEGG, and the immune infiltration of CAPNs by ssGSEA. RESULTS: Our results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. CAPN1, 5, 8, and 12 expression levels were positively correlated with individual cancer stages. Furthermore, CAPN1, 2, 5, and 8 expression levels were negatively correlated with overall survival (OS) and recurrence-free survival (RFS), while CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumor-infiltrating T follicular helper cells and CAPN10 with tumor-infiltrating T helper 2 cells. Functional enrichment analysis showed that differentially expressed CAPNs (CAPN1, 2, 5, 8, and 10) are involved in axonogenesis, cell-substrate adhesion, immune response-activating cell surface receptor signaling pathway, and cell junction organization in PC. CONCLUSIONS: These results suggested that CAPN1, 2, 5, 8, and 10 could be used as prognostic biomarkers in PC and improve individualized treatment strategies.

Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is often characterized by poor prognosis, high invasiveness and chemotherapeutic resistance, and its migration is strongly dependent on the specific tumor microenvironment. Fibroblasts, such as cancer-associated stromal fibroblasts (CAFs), are the main supporting cells in the tumor microenvironment. Thus, an understanding of how these cells communicate is required for HCC treatment. METHODS: CAFs and paracancerous fibroblasts (PAFs) were isolated from patients' surgical specimens, followed by exosome isolation and miRNA sequencing. The expression levels of miR-29b in different cell groups were detected by qPCR assay. Cell transfection with exogenous miRNAs was used to study whether the stromal cells could transfer miRNAs to HCC cells. Based on the preliminary results, a miR-29b mimic, inhibitor or miR-nonspecific mimic (miR-NSM) was further transfected into HepG2 and Huh7 cells prior to scratch wound healing and cell invasion experiments. Finally, the transfected cells were stained with Hoechst 33348. RESULTS: The direct transfer of miR-29b from CAFs to HCC cells through an exosome was observed in this study. DNA methyltransferase 3b (DNMT3b) expression was directly inhibited by miR-29b, while metastasis suppressor 1 (MTSS1) expression was upregulated in HCC cells. Such changes further induced growth arrest and inhibited HCC cell invasion. CONCLUSIONS: Exosomal miR-29b from CAFs can play a crucial role in the development, progression and metastasis of HCC. By functioning as a tumor suppressor that targets DNMT3b, miR-29b may serve as a potential therapeutic agent.

Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC.

BACKGROUND: Combined hepatectomy and radiofrequency ablation (RFA) provides an additional treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) who are conventionally deemed unresectable. This study aimed to analyze the outcome of this combination therapy by comparing it with transarterial chemoembolization (TACE). METHODS: We retrospectively reviewed 51 patients with unresectable BCLC stage B HCC who had received the combination therapy. We compared the survival of these patients with that of 102 patients in the TACE group (control). Prognostic factors associated with worse survival in the combination group were analyzed. RESULTS: No differences in tumor status and liver function were observed between the TACE group and combination group. The median survival time for the combination group and TACE group was 38 (6-54) and 17 (3-48) months, respectively (P<0.001). The combination group required longer hospitalization than the TACE group [8 (5-14) days vs 4 (2-9) days, P<0.001]. More than two ablations decreased the survival rate in the combination group. CONCLUSIONS: Combined hepatectomy and RFA yielded a better long-term outcome than TACE in patients with unresectable BCLC stage B HCC. Patients with a limited ablated size (≤2 cm), a limited number of ablations (≤2), and adequate surgical margin should be considered candidates for combination therapy.