Systematic evaluation of the effect of polyadenylation signal variants on the expression of disease-associated genes.

Single nucleotide variants (SNVs) within polyadenylation signals (PASs), a specific six-nucleotide sequence required for mRNA maturation, can impair RNA-level gene expression and cause human diseases. However, there is a lack of genome-wide investigation and systematic confirmation tools for identifying PAS variants. Here, we present a computational strategy to integrate the most reliable resources for discovering distinct genomic features of PAS variants and also develop a credible and convenient experimental tool to validate the effect of PAS variants on expression of disease-associated genes. This approach will greatly accelerate the deciphering of PAS variation-related human diseases.

circPSD3 is a promising inhibitor of uPA system to inhibit vascular invasion and metastasis in hepatocellular carcinoma.

BACKGROUND: Vascular invasion is a major route for intrahepatic and distant metastasis in hepatocellular carcinoma (HCC) and is a strong negative prognostic factor. Circular RNAs (circRNAs) play important roles in tumorigenesis and metastasis. However, the regulatory functions and underlying mechanisms of circRNAs in the development of vascular invasion in HCC are largely unknown. METHODS: High throughput sequencing was used to screen dysregulated circRNAs in portal vein tumor thrombosis (PVTT) tissues. The biological functions of candidate circRNAs in the migration, vascular invasion, and metastasis of HCC cells were examined in vitro and in vivo. To explore the underlying mechanisms, RNA sequencing, MS2-tagged RNA affinity purification, mass spectrometry, and RNA immunoprecipitation assays were performed. RESULTS: circRNA sequencing followed by quantitative real-time PCR (qRT-PCR) revealed that circRNA pleckstrin and Sect. 7 domain containing 3 (circPSD3) was significantly downregulated in PVTT tissues. Decreased circPSD3 expression in HCC tissues was associated with unfavourable characteristics and predicted poor prognosis in HCC. TAR DNA-binding protein 43 (TDP43) inhibited the biogenesis of circPSD3 by interacting with the downstream intron of pre-PSD3. circPSD3 inhibited the intrahepatic vascular invasion and metastasis of HCC cells in vitro and in vivo. Serpin family B member 2 (SERPINB2), an endogenous bona fide inhibitor of the urokinase-type plasminogen activator (uPA) system, is the downstream target of circPSD3. Mechanistically, circPSD3 interacts with histone deacetylase 1 (HDAC1) to sequester it in the cytoplasm, attenuating the inhibitory effect of HDAC1 on the transcription of SERPINB2. In vitro and in vivo studies demonstrated that circPSD3 is a promising inhibitor of the uPA system. CONCLUSIONS: circPSD3 is an essential regulator of vascular invasion and metastasis in HCC and may serve as a prognostic biomarker and therapeutic target.

A circular RNA produced by LRBA promotes cirrhotic mouse liver regeneration through facilitating the ubiquitination degradation of p27.

BACKGROUND AND AIMS: Accumulating circular RNAs (circRNAs) play important roles in tissue repair and organ regeneration. However, the biological effects of circRNAs on liver regeneration remain largely unknown. This study aims to systematically elucidate the functions and mechanisms of circRNAs derived from lipopolysaccharide-responsive beige-like anchor protein (LRBA) in regulating liver regeneration. METHODS: CircRNAs derived from mouse LRBA gene were identified using CircBase. In vivo and in vitro experiments were conducted to confirm the effects of circLRBA on liver regeneration. RNA pull-down and RNA immunoprecipitation assays were used to investigate the underlying mechanisms. Clinical samples and cirrhotic mouse models were used to evaluate the clinical significance and transitional value of circLRBA. RESULTS: Eight circRNAs derived from LRBA were registered in CircBase. The circRNA mmu_circ_0018031 (circLRBA) was significantly upregulated in the liver tissues after 2/3 partial hepatectomy (PHx). Adeno-associated virus serotype 8 (AAV8)-mediated knockdown of circLRBA markedly inhibited mouse liver regeneration after 2/3 PHx. In vitro experiments confirmed that circLRBA exerted its growth-promoting function mainly through liver parenchymal cells. Mechanistically, circLRBA acted as a scaffold for the interaction between E3 ubiquitin-protein ligase ring finger protein 123 and p27, facilitating the ubiquitination degradation of p27. Clinically, circLRBA was lowly expressed in cirrhotic liver tissues and negatively correlated with perioperative levels of total bilirubin. Furthermore, overexpression of circLRBA enhanced cirrhotic mouse liver regeneration after 2/3 PHx. CONCLUSIONS: We conclude that circLRBA is a novel growth promoter in liver regeneration and a potential therapeutic target related to deficiency of cirrhotic liver regeneration.

NONCODEV6: an updated database dedicated to long non-coding RNA annotation in both animals and plants.

NONCODE (http://www.noncode.org/) is a comprehensive database of collection and annotation of noncoding RNAs, especially long non-coding RNAs (lncRNAs) in animals. NONCODEV6 is dedicated to providing the full scope of lncRNAs across plants and animals. The number of lncRNAs in NONCODEV6 has increased from 548 640 to 644 510 since the last update in 2017. The number of human lncRNAs has increased from 172 216 to 173 112. The number of mouse lncRNAs increased from 131 697 to 131 974. The number of plant lncRNAs is 94 697. The relationship between lncRNAs in human and cancer were updated with transcriptome sequencing profiles. Three important new features were also introduced in NONCODEV6: (i) updated human lncRNA-disease relationships, especially cancer; (ii) lncRNA annotations with tissue expression profiles and predicted function in five common plants; iii) lncRNAs conservation annotation at transcript level for 23 plant species. NONCODEV6 is accessible through http://www.noncode.org/.

Effect of chest ultrasound compared with pericardial window for the diagnosis of occult penetrating cardiac wounds in hemodynamically stable subjects with penetrating thoracic trauma: A meta-analysis.

We conducted a meta-analysis to assess the diagnostic performance of chest ultrasound compared with a pericardial window for the detection of occult penetrating cardiac wounds in patients with penetrating thoracic trauma who were hemodynamically stable. A systematic literature search up to December 2022 was performed and 567 related studies were evaluated. The chosen studies comprised 629 penetrating thoracic trauma subjects who participated in the selected studies' baseline. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of different chest ultrasounds on wound infection after penetrating thoracic trauma by the dichotomous methods with a random or fixed effect model. The chest ultrasound resulted in significantly lower occult penetrating cardiac wounds detection (OR, 0.02; 95% CI, 0.01-0.08, P < 0.001), higher false positive (OR, 33.85; 95% CI, 9.21-124.39, P < 0.001), and higher false negative (OR, 27.31; 95% CI, 7.62-97.86, P < 0.001) compared with the pericardial window in penetrating thoracic trauma. The chest ultrasound resulted in significantly lower occult penetrating cardiac wound detection, higher false positives, and higher false negatives compared with the pericardial window in penetrating thoracic trauma. Although care should be taken when dealing with the results because all of the studies had less than 200 subjects as a sample size.

Advantages of laparoscopic hepatic hemangioma surgery in quality of life: a prospective study.

BACKGROUND: Surgical intervention is the most accurate method for the treatment of hepatic hemangioma. The advantages of laparoscopic surgery on quality of life should be clarified by prospective studies. METHODS: The sample sizes of the laparoscopic and open surgery groups were calculated based on previous retrospective literature. Intraoperative and postoperative parameters were prospectively collected and analyzed. Quality of life in both groups was predicted by a mixed linear model. RESULTS: Sixty patients were enrolled in the laparoscopic surgery group and open surgery group. The laparoscopic group had a longer operation time (P = 0.040) and more hospitalization expenses (P = 0.001); however, the Clavien-Dindo classification and comprehensive complication index suggested a lower incidence of surgical complications in the laparoscopic group, with P values of 0.049 and 0.002, respectively. After mixed linear model prediction, between-group analysis indicated that the laparoscopic group had little impact on role-physical functioning and role-emotional functioning; in addition, within-group analysis showed a rapid recovery time on role-physical functioning and role-emotional functioning in the laparoscopic group. Quality of life in both groups recovered to the preoperative level within 1 year after the operation. CONCLUSION: The advantages of laparoscopic hepatectomy for hepatic hemangioma were fewer postoperative complications, lower impact on quality of life and faster recovery from affected quality of life.

Preoperative and postoperative nomograms for predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection.

BACKGROUND: Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. METHODS: Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. RESULTS: In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. CONCLUSIONS: The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.

Novel postoperative nomograms for predicting individual prognoses of hepatitis B-related hepatocellular carcinoma with cirrhosis.

BACKGROUND: Liver cirrhosis is a well-known risk factor for carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to construct individual prognostic models for HCC with cirrhosis. METHODS: The clinical differences between HCC patients with and without cirrhosis were compared using a large cohort of 1003 cases. The patients with cirrhosis were randomly divided into a training cohort and a validation cohort in a ratio of 2:1. Univariate and multivariate analyses were performed to reveal the independent risk factors for recurrence-free survival (RFS) and overall survival (OS) in HCC patients with cirrhosis. These factors were subsequently used to construct nomograms. RESULTS: Multivariate analyses revealed that five clinical variables (hepatitis B e antigen (HBeAg) positivity, alpha-fetoprotein (AFP) level, tumour diameter, microvascular invasion (MVI), and satellite lesions) and seven variables (HBeAg positivity, AFP level, tumour diameter, MVI, satellite lesions, gamma-glutamyl transpeptidase level, and histological differentiation) were significantly associated with RFS and OS, respectively. The C-indices of the nomograms for RFS and OS were 0.739 (P < 0.001) and 0.789 (P < 0.001), respectively, in the training cohort, and 0.752 (P < 0.001) and 0.813 (P < 0.001), respectively, in the validation cohort. The C-indices of the nomograms were significantly higher than those of conventional staging systems (P < 0.001). The calibration plots showed optimal consistence between the nomogram-predicted and observed prognoses. CONCLUSIONS: The nomograms developed in the present study showed good performance in predicting the prognoses of HCC patients with hepatitis B virus-associated cirrhosis.

Causal influences of neuroticism on mental health and cardiovascular disease.

We investigated the relationship between neuroticism and 16 mental and 18 physical traits using summary results of genome-wide association studies for these traits. LD score regression was used to investigate genetic correlations between neuroticism and the 34 health outcomes. Mendelian randomization was performed to investigate mutual causal relationships between neuroticism and the 34 health outcomes. Neuroticism genetically correlates with a majority of health-related traits and confers causal effects on 12 mental traits (major depressive disorder (MDD), insomnia, subjective well-being (SWB, negatively), schizophrenia, attention-deficit/hyperactivity disorder, alcohol dependence, loneliness, anorexia nervosa, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, and psychiatric disorders) and two physical diseases (cardiovascular disease and hypertensive disease). Conversely, MDD, SWB, and insomnia have a causal effect on neuroticism. We highlighted key genes contributing to the causal associations between neuroticism and MDD, including RBFOX1, RERE, SOX5, and TCF4, and those contributing to the causal associations between neuroticism and cardiovascular diseases, including MAD1L1, ARNTL, RERE, and SOX6. The present study indicates that genetic variation mediates the causal influences of neuroticism on mental health and cardiovascular diseases.

Associations between maternal vitamin D status during three trimesters and cord blood 25(OH)D concentrations in newborns: a prospective Shanghai birth cohort study.

PURPOSE: Prenatal vitamin D (VitD) deficiency influences children's health in later life. We aimed to test the associations between maternal VitD status in each of the three trimesters of pregnancy and cord blood 25(OH)D concentrations in newborns. METHODS: Participants were pregnant women recruited from the Shanghai Birth Cohort (SBC) (n = 1100). Of all the participants, 946 completed the collection of venous blood at early (< 16 weeks, T1), mid- (24-28 weeks, T2), and late (32-34 weeks, T3) pregnancy as well as the corresponding cord blood in the newborns. Maternal serum 25(OH)D concentrations were measured by LC-MS/MS, and the information on confounding factors was obtained through a standardized questionnaire. RESULTS: The mean 25(OH)D concentrations at time points T1, T2, T3 in maternal blood and cord blood of the newborns were 26.31 ng/mL, 31.92 ng/mL, 35.62 ng/mL, and 19.77 ng/mL, respectively. Neonatal 25(OH)D level in cord blood was positively correlated with maternal serum 25(OH)D levels at each trimester, and the strongest correlation was found at time point T3. CONCLUSION: Maternal 25(OH)D concentrations at each trimester were positively associated with neonatal VitD status in cord blood, and the strongest correlation was found in the late stage of pregnancy, which could be considered as a sensitive time window. Attention should be paid to the nutritional status of VitD during pregnancy to better prevent the VitD deficiency in neonates.

A multi-model deep convolutional neural network for automatic hippocampus segmentation and classification in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and irreversible brain degenerative disorder. Mild cognitive impairment (MCI) is a clinical precursor of AD. Although some treatments can delay its progression, no effective cures are available for AD. Accurate early-stage diagnosis of AD is vital for the prevention and intervention of the disease progression. Hippocampus is one of the first affected brain regions in AD. To help AD diagnosis, the shape and volume of the hippocampus are often measured using structural magnetic resonance imaging (MRI). However, these features encode limited information and may suffer from segmentation errors. Additionally, the extraction of these features is independent of the classification model, which could result in sub-optimal performance. In this study, we propose a multi-model deep learning framework based on convolutional neural network (CNN) for joint automatic hippocampal segmentation and AD classification using structural MRI data. Firstly, a multi-task deep CNN model is constructed for jointly learning hippocampal segmentation and disease classification. Then, we construct a 3D Densely Connected Convolutional Networks (3D DenseNet) to learn features of the 3D patches extracted based on the hippocampal segmentation results for the classification task. Finally, the learned features from the multi-task CNN and DenseNet models are combined to classify disease status. Our method is evaluated on the baseline T1-weighted structural MRI data collected from 97 AD, 233 MCI, 119 Normal Control (NC) subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The proposed method achieves a dice similarity coefficient of 87.0% for hippocampal segmentation. In addition, the proposed method achieves an accuracy of 88.9% and an AUC (area under the ROC curve) of 92.5% for classifying AD vs. NC subjects, and an accuracy of 76.2% and an AUC of 77.5% for classifying MCI vs. NC subjects. Our empirical study also demonstrates that the proposed multi-model method outperforms the single-model methods and several other competing methods.

Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study.

BACKGROUND AND PURPOSE: Previous studies have found ischemic stroke is associated with atrial fibrillation. However, the causal association between ischemic stroke and atrial fibrillation is not clear. Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention. This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation. METHODS: Summary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height). Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies. Inverse-variance weighted method was performed to estimate causal effect. RESULTS: Blood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation. The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07; P = 1.3 × 10-5). One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034, P = 0.029; SBP: 95% CI, 0.006 to 0.034, P = 0.003) upper systolic and diastolic blood pressure levels. Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35; P = 0.012. SBP: RR, 1.18; 95% CI, 1.01 to 1.38; P = 0.04). Specially, we also found the bidirectional causality between blood pressure and ischemic stroke. CONCLUSIONS: Our study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.

LEPR hypomethylation is significantly associated with gastric cancer in males.

BACKGROUND: Previous study has shown LEPR is a candidate gene of prediction and treatment of gastric cancer (GC). The purpose of this study was to test whether LEPR methylation could predict the risk of GC. MATERIALS AND METHODS: Tumor tissues and 5-cm adjacent non-tumor tissues from 117 newly diagnosed and untreated GC patients were collected for the current methylation study. LEPR methylation levels were determined by quantitative methylation specific PCR (qMSP), and the methylation level of LEPR was described by the percentage of methylated reference (PMR). RESULTS: Our results showed that LEPR methylation levels were significantly lower in tumor tissues than those in adjacent non-tumor tissues (median PMR: 36.64% vs. 50.29%, P = 1E-4). In addition, LEPR methylation levels were found to be significantly associated with platelet (r = -0.198, P = .037). Further subgroup analysis showed that the association of LEPR promoter hypomethylation with GC was specific to males (males: P = 7E-5; females: P = .500). Notably, significant hypomethylation of LEPR promoter was found only in GC patients without recurrence (P = .002) but not in GC patients with recurrence (P = .146). The AUC of LEPR hypomethylation for identification of GC risk was 0.649 with a sensitivity of 67.5% and a specificity of 63.2%. In addition, the AUC of LEPR hypomethylation in males was 0.685 with a sensitivity of 68.4% and a specificity of 69.6%. CONCLUSION: LEPR hypomethylation can be used to predict the risk of GC in males. And it might also have the potential to predict the recurrence in GC patients.

Deletion of c16orf45 in zebrafish results in a low fertilization rate and increased thigmotaxis.

c16orf45 is located at 16p13.11, an important locus related to neurodevelopmental diseases. Clinical studies have demonstrated that c16orf45 is associated with various neurodevelopmental diseases. To further elucidate the effect of c16orf45 on neural development, we constructed a zebrafish model with a stably inherited c16orf45 deletion via CRISPR/Cas9 technology. We found that deletion of c16orf45 significantly reduced the zebrafish fertilization rate, and both females and males showed reduced fertility. Meanwhile, the homozygous c16orf45 knockout zebrafish showed a developmental delay at 24 hr postfertilization (hpf). However, morphological changes were not apparent after 2 days postfertilization (dpf). Notably, the results of behavioral experiments revealed increased thigmotaxis in c16orf45-/- zebrafish at 2 months. In conclusion, these findings demonstrate that c16orf45 plays an important role in nervous system and reproductive system.

SETD3 is regulated by a couple of microRNAs and plays opposing roles in proliferation and metastasis of hepatocellular carcinoma.

A previous study reported that histone methyltransferase SETD3 is up-regulated in tumor tissues of hepatocellular carcinoma (HCC) and is associated with the growth of HCC. However, the clinical significance and the effect of SETD3 on HCC metastasis remain unclear. In the present study, both the protein and mRNA expression levels of SETD3 were measured in a larger cohort of HCC patients. The results showed that the protein level of SETD3 in HCC tissues was significantly higher than that in non-tumorous tissues, which was inconsistent with the mRNA expression level of SETD3. The high protein level of SETD3 in HCC tissues was significantly associated with male gender, poor pathological differentiation, liver cirrhosis and unfavorable prognosis of HCC patients. Subsequently, we demonstrated that SETD3 could be regulated at post-transcriptional step by a couple of miRNAs (miR-16, miR-195 and miR-497). Additionally, in vitro and in vivo experiments revealed that SETD3 played opposing roles in proliferation and metastasis of HCC: promoting proliferation but inhibiting metastasis. Mechanistic experiments revealed that doublecortin-like kinase 1 (DCLK1) was a downstream target of SETD3. SETD3 could increase the DNA methylation level of DCLK1 promoter to inhibit the transcription of DCLK1. Further study revealed that DCLK1/PI3K/matrix metalloproteinase (MMP) 2 (MMP-2) was an important pathway that mediated the effect of SETD3 on HCC metastasis. In conclusion, the present study revealed that SETD3 is associated with tumorigenesis and is a promising biomarker for predicting the prognosis of HCC patients after surgical resection. In addition, SETD3 plays inhibitory role in HCC metastasis partly through DCLK1/PI3K/MMP-2 pathway.

Outcomes of pure laparoscopic Glissonian pedicle approach hepatectomy for hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: Few studies had been performed to concern the outcomes of pure laparoscopic Glissonian pedicle approach hepatectomy (LGAH) for hepatocellular carcinoma (HCC). The aim of this study was to compare the outcomes of LGAH versus open Glissonian pedicle approach hepatectomy (OGAH) for HCC, especially in patients with cirrhosis. METHODS: Hepatocellular carcinoma patients who underwent pure LGAH and OGAH between January 2015 and July 2017 in our institution were retrospectively enrolled in this study. Propensity score matching (PSM) of patients in a ratio of 1:1 was conducted to adjust the known confounders. The perioperative and oncological outcomes were compared between the two groups after PSM. RESULTS: Some 80 patients underwent pure LGAH and 134 had OGAH. After PSM, 67 patients in each group were well matched for analysis. Both the postoperative overall complication rates (13.4% vs. 29.9%, P = 0.021) and mean comprehensive complication index (2.63 vs. 7.40, P = 0.035) were significantly lower in the LGAH group than those in OGAH group. Although the operative time was longer in the LRH group (P < 0.001), the length of postoperative hospital stay was shorter in the LRH group (P = 0.024). Furthermore, both the 3-year overall survival rate (73.3% for LGAH vs. 77.8% for OGAH, P = 0.338) and 3-year disease-free survival rate (56.4% for LGAH vs. 62.5% for OGAH, P = 0.455) were not significantly different between the groups. CONCLUSION: Pure laparoscopic Glissonian approach may be a better alternative to open Glissonian approach in selected HCC patients, which provided fewer complications, shorter postoperative hospital stay and comparable oncological outcomes.

The microRNA-375 as a potentially promising biomarker to predict the prognosis of patients with head and neck or esophageal squamous cell carcinoma: a meta-analysis.

BACKGROUND: The prognostic value of microRNA-375 (miR-375) expression in squamous cell carcinoma (SCC) had been reported in the previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic significance of miR-375 expression in SCC based on all eligible evidences. METHODS: Relevant studies were identified by searching PubMed, Embace, Medline, Cochrane Library, and China Biology Medicine disk. Survival outcome including overall survival (OS) and other survival outcomes were used as the primary endpoint to evaluate the prognostic outcome of patients with SCC. All statistical analyses were performed in RevMan software version 5.3 and STATA software version 14.1. Furthermore, the quality of included studies was assessed by The Newcastle-Ottawa Scale. RESULTS: In total, 13 studies, including 1340 patients, met the inclusion criteria for our meta-analysis. The pooled analysis results indicated that downregulation of miR-375 significantly predicted poor OS (HR 1.58, 95% CI 1.34-1.88, P < 0.001). Downregulated miR-375 was also correlated with the other survival outcomes. Subgroup analysis based on tumor type found that lower expression of miR-375 was significantly related with poor OS in patients with esophageal squamous cell carcinoma (ESCC) (HR 1.58, 95% CI 1.29-1.94, P < 0.001) and head and neck squamous cell carcinoma (HNSCC) (HR 1.59, 95% CI 1.16-2.18, P = 0.004). CONCLUSIONS: This meta-analysis demonstrated that the downexpression of miR-375 was significantly correlated with poor OS in patients with SCCs and indicated the potential clinical use of miR-375 as a molecular biomarker, particularly in assessing prognosis for patients with ESCC and HNSCC.

A novel combined systemic inflammation-based score can predict survival of intermediate-to-advanced hepatocellular carcinoma patients undergoing transarterial chemoembolization.

BACKGROUND: There is currently limited information regarding the prognostic ability of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) for hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of the dNLR-PNI in patients with intermediate-to-advanced HCC after transarterial chemoembolization (TACE). METHODS: A total of 761 HCC patients were enrolled in the study. The dNLR-PNI was retrospectively calculated in these patients, as follows: patients with both an elevated dNLR and a decreased PNI, as determined using the cutoffs obtained from receiver operating characteristic curve analysis, were allocated a score of 2, while patients showing one or neither of these alterations were allocated a score of 1 or 0, respectively. RESULTS: During the follow-up period, 562 patients died. Multivariate analysis suggested that elevated total bilirubin, Barcelona Clinic Liver Cancer C stage, repeated TACE, and dNLR-PNI were independently associated with unsatisfactory overall survival. The median survival times of patients with a dNLR-PNI of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 22.5-39.5), 16.0 (95% CI 12.2-19.7) and 6.0 (95% CI 4.8-7.2) months, respectively (P < 0.001). CONCLUSIONS: The dNLR-PNI can predict the survival outcomes of intermediate-to-advanced HCC patients undergoing TACE, and should be further evaluated as a prognostic marker for who are to undergo TACE treatment.

LigaSure versus CUSA for parenchymal transection during laparoscopic hepatectomy in hepatocellular carcinoma patients with cirrhosis: a propensity score-matched analysis.

BACKGROUND: LigaSure has been reported as a safe and effective approach for parenchymal transection in open hepatectomy; however, its roles in laparoscopic hepatectomy (LH) with liver cirrhosis have not been evaluated. The aim of this study was to compare the outcomes of LigaSure vs. Cavitron Ultrasonic Surgical Aspirator (CUSA) for LH in hepatocellular carcinoma (HCC) patients with cirrhosis. METHODS: We retrospectively reviewed the medical records of 135 HCC patients with background cirrhosis who underwent pure LH using CUSA (n = 55) or LigaSure (n = 80) for parenchymal transection between January 2015 and May 2017 at West China Hospital of Sichuan University. We performed 1:1 propensity score matching between the LigaSure and CUSA groups. Subsequently, 48 patients were included in each group. RESULTS: The mean parenchymal transection time (74.3 ± 23.6 vs. 86.3 ± 25.8 min, P = 0.019) in the LigaSure group was obviously shorter than that in the CUSA group. The LigaSure did not increase the intraoperative blood loss or blood transfusion requirement when compared with CUSA. Moreover, the degree of postoperative reperfusion injury and complications were not significantly different between the two groups. Furthermore, there were no significant differences between the two groups regarding 2-year overall survival rate or disease-free survival rate. In addition, the total hospitalization costs (P = 0.032) and intraoperative costs (P = 0.006) per case were significantly lower in the LigaSure group than those in the CUSA group. CONCLUSION: The two devices were safe and effective for LH in patients with cirrhosis. The LigaSure method may be a simple, feasible, and cost-effective surgical technique for LH in selected HCC patients with cirrhosis.

Postoperative Albumin-Bilirubin Grade Change Predicts the Prognosis of Patients with Hepatitis B-Related Hepatocellular Carcinoma Within the Milan Criteria.

OBJECTIVE: Albumin-bilirubin (ALBI) grade has been validated as a simple, evidence-based, and objective prognostic tool for patients with hepatocellular carcinoma (HCC). However, minimal information is available concerning postoperative ALBI grade changes in HCC. This study aimed to investigate the prognostic value of postoperative ALBI grade changes in patients with hepatitis B virus (HBV)-related HCC within the Milan criteria after liver resection. METHODS: Patients with HBV-related HCC within the Milan criteria who underwent liver resection between 2010 and 2016 at West China Hospital were reviewed (N = 258). A change in ALBI grade was defined as first postoperative month ALBI grade-preoperative ALBI grade. If the value was >0, postoperative worsening of ALBI grade was considered; otherwise, stable ALBI grade was considered. Cox proportional hazard regression analyses were used to determine the factors that influence recurrence and survival. RESULTS: During the follow-up, 130 patients experienced recurrence and 47 patients died. Multivariate analyses revealed that postoperative worsening of ALBI grade (HR 1.541, 95% CI 1.025-2.318, P = 0.038), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P = 0.004), and multiple tumors (HR 1.676, 95% CI 1.075-2.615, P = 0.023) were associated with postoperative recurrence, whereas MVI (HR 2.737, 95% CI 1.475-5.080, P = 0.001), postoperative worsening of ALBI grade (HR 2.268, 95% CI 1.227-4.189, P = 0.009), high alpha-fetoprotein level (HR 2.055, 95% CI 1.136-3.716, P = 0.017), and transfusion (HR 2.597, 95% CI 1.395-4.834, P = 0.003) negatively influenced long-term survival. Patients with postoperative worsening of ALBI grade exhibited increased incidence of recurrence and worse long-term survival. CONCLUSION: Postoperative worsening of ALBI grade was associated with increased recurrence and poorer overall survival for patients with HBV-related HCC within the Milan criteria. We should pay attention to liver function changes in HCC patients after liver resection.