Identifying Proliferative Hepatocellular Carcinoma at Pretreatment CT: Implications for Therapeutic Outcomes after Transarterial Chemoembolization.

Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model. Materials and Methods This retrospective multicenter study included adults with HCC who underwent liver resection or cTACE between August 2013 and December 2020. A CT-based predictive model for identifying proliferative HCCs was developed and externally validated in a cohort that underwent resection. Diagnostic performance was calculated for the model. Thereafter, patients in the cTACE cohort were stratified into groups with predicted proliferative or nonproliferative HCCs according to the model. The primary outcome was overall survival (OS), and the secondary outcomes were tumor response rate and progression-free survival (PFS). These were compared between the two groups with use of the χ2 test and the log-rank test. Results A total of 1194 patients (1021 men; mean age, 54 years ± 12 [SD]; median follow-up time, 29.1 months) were included. The predictive model, named the SMARS score, incorporated lobulated shape, mosaic architecture, α-fetoprotein levels, rim arterial phase hyperenhancement, and satellite lesions. The area under the receiver operating characteristic curve for the SMARS score was 0.83 for the training cohort and 0.80 for the validation cohort. According to the SMARS score, patients with predicted proliferative HCCs (n = 114) had lower tumor response rate (48% vs 71%; P < .001) and worse PFS (6.6 months vs 12.4 months; P < .001) and OS (14.4 months vs 38.7 months; P < .001) than those with nonproliferative HCCs (n = 263). Conclusion The predictive model demonstrated good performance for identifying proliferative HCCs. According to the SMARS score, patients with predicted proliferative HCCs have worse prognosis than those with predicted nonproliferative HCCs after cTACE. © RSNA, 2023 Supplemental material is available for this article.

An Integrated Liver Function, Systemic Inflammation, and Tumor Characteristic Score Predicts Prognosis in Hepatocellular Carcinoma After Curative Resection.

BACKGROUND: Several scoring systems are currently used to predict prognosis of hepatocellular carcinoma (HCC), but none of them integrates liver function, systemic inflammation, and tumor characteristics in a unified model. The current study aimed to develop and validate a novel prognostic score that integrates liver function, systemic inflammation, and tumor characteristics in a unified model to predict the prognosis of HCC after curative resection. METHODS: Patients with HCC who underwent curative liver resection were included in a training set (n = 1027). Multivariate Cox regression was performed to determine the risk factors for a poor prognosis. A prognostic score was developed by assigning points for risk factors in proportion to beta coefficients in a Cox multivariable model. Predictive performance and distinction ability of the prognostic score were further evaluated in two independent validation cohorts treated with either curative resection (n = 281) or transarterial chemoembolization (TACE) (n = 404) and compared with 16 other models. RESULTS: The prognostic predictive system, named the function-inflammation-burden-alpha-fetoprotein (FIBA) score, was derived by assigning points for six independent predictors including albumin, total bilirubin, lymphocyte count, diameter of the largest tumor, number of tumors, and alpha-fetoprotein (AFP). The FIBA score showed an outperformed predictive value compared with other systems in both training and validation cohorts by giving the highest C-index, likelihood ratio chi-square values, and Wald test values as well as the lowest Akaike information criterion. CONCLUSION: The FIBA score can be used to stratify HCC patients treated with curative resection. Meanwhile, the FIBA score performs well against other prognostic scoring systems and is potentially broadly applicable to a TACE-treated patient cohort.

Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis.

BACKGROUND: Intestinal micro-ecological imbalances impair the intestinal barrier and induce intestinal inflammation, for example, ulcerative colitis (UC). According to the latest research, abnormalities in intestinal microbiota structure and their metabolites play a dominant role in UC progression; in addition, they could affect the mucus barrier based on different factors. Although numerous studies have confirmed the important role of intestinal microbiota in UC pathogenesis, the intricate connection between microbiota and metabolites and mucus barrier in UC occurrence remains unclear, and correlation analyses of differential microbiota and their metabolites under UC are relatively scarce. AIM: To reveal the differential intestinal microbiota and metabolites in UC pathogenesis and explore more sensitive biomarker compositions. METHODS: We used the antibiotic combination method to establish intestinal pseudo-aseptic mice; afterward, dextran sulfate sodium (DSS) was applied to establish an acute experimental colitis mice model. Colitis severity, assessed based on disease activity index, colorectal length, colorectal wet weight, and histological lesions, and mucus-related staining (mucopolysaccharide alcian blue and immunofluorescence of mucin), was compared between the pseudo-aseptic and bacterial colitis mice. Finally, differential intestinal microbiota, metabolites, and their association and correlations, were analyzed by 16s rDNA sequencing in combination with non-targeted metabolomics, through gas chromatography-mass spectrometry. RESULTS: Compared with the pseudo-aseptic mice, intestinal bacteria positive mice were more severely ill and their intestinal mucus loss was more pronounced in DSS-induced colitis (P < 0.05), suggesting that different microbiota and metabolites could cause the different degrees of colitis. Subsequently, we observed that in addition to Klebsiella, and Bacteroides, which were widely associated with colitis, Candidatus Stoquefichus, Anaerobiospirillum, Muribaculum, and Negativibacillus may be involved in protection against colitis. Furthermore, differential metabolites of the microbiota were mainly enriched in the synthesis-related pathways of key structural sequences of mucin. In combination with the mucin-related staining and immunofluorescence results, the findings indicate that the differential microbiota and their metabolites potentially regulate the composition and function of mucus under colitis. CONCLUSION: Microbiota and their metabolites are major factors regulating the composition and function of mucus, in turn influencing the function and structure of intestinal mucus barrier under colitis. The different microbiota and metabolites identified in the present study could be novel biomarkers for colitis.

Liver resection versus microwave ablation for hepatocellular carcinoma in ideal candidates for ablation per Barcelona Clinic Liver Cancer staging: a propensity score matching and inverse probability of treatment weighting analysis.

BACKGROUND: Liver resection (LRE) and microwave ablation (MWA) for hepatocellular carcinoma (HCC) have been widely compared. AIMS: To compare the therapeutic outcomes of percutaneous MWA and LRE for HCC in ideal candidates for ablation according to Barcelona Clinic Liver Cancer (BCLC) staging METHODS: Between August 2013 and November 2020, 483 consecutive patients meeting criteria for "ideal candidates for ablation" per the BCLC staging initially treated with MWA (n = 168) or LRE (n = 315) were included. Patients were further divided into BCLC-0 (n = 116) and BCLC-A (n = 367) groups. Overall survival (OS), recurrence-free survival (RFS) and post-procedure-related complication rates were compared before and after propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) in the overall population and subgroups. Multivariate Cox regression analysis was performed to determine whether the treatment modality was an independent prognostic factor. RESULTS: LRE had a better RFS and similar OS and post-procedure-related complication rates compared to MWA in the overall population and in the BCLC-A subgroup both before and after PSM and IPTW. However, the OS, RFS and post-procedure-related complication rates were equivalent between the two groups before and after PSM and IPTW in patients with BCLC-0 disease. The multivariate Cox regression analysis showed that LRE was associated with better RFS over MWA in overall population (p = 0.003; HR = 0.67; 95% CI: 0.51-0.87) and BCLC-A disease (p = 0.046; HR = 0.74; 95% CI: 0.56-0.99), while it did not differ in OS. CONCLUSION: An 'ideal candidate for ablation' according to the BCLC staging system may not be an ideal candidate for MWA. However, patients with BCLC-0 may be the optimal population for MWA.

Ideal patients for liver resection in Barcelona Clinic Liver Cancer or Hong Kong Liver clinic systems for hepatocellular carcinoma: Conservative or aggressive?

Background: Both the Barcelona Clinic Liver Cancer (BCLC) staging and the Hong Kong Liver Cancer (HKLC) staging have their own definitions of ideal patients for liver resection (IPLR) in hepatocellular carcinoma (HCC). This study aimed to compare the prognosis of IPLRs between the BCLC and HKLC staging systems, and to identify patients who may benefit from liver resection (LR) in the HKLC staging but beyond the BCLC staging. Methods: This retrospective study evaluated 1,296 consecutive patients with HCC who underwent LR between August 2013 and April 2021 (457 patients and 1,046 patients were IPLR according to the BCLC and HKLC staging systems, respectively). Overall survival (OS) was compared between the two groups. To assess potential benefit of LR for IPLR in the HKLC staging but beyond the BCLC staging, univariate and multivariate Cox regression analysis was performed to determine prognostic factors of OS, and prognostic stratification was performed based on the selected prognostic factors. The IPLRs in the HKLC staging but beyond the BCLC staging were divided into subgroups according to the prognostic stratification and separately compared with the IPLRs in the BCLC staging. Results: OS was different between the two staging systems (P = 0.011). All the 457 IPLRs in the BCLC staging were also the IPLRs in the HKLC staging. Diameter of the largest tumor5 cm (HR = 1.58; 95% CI: 1.18-2.10; P = 0.002) and liver cirrhosis (HR = 1.61; 95% CI: 1.19-2.20; P = 0.002) were risk factors for poor OS in IPLRs in the HKLC staging but beyond the BCLC staging; hence, patients were divided into the low-risk (n = 104), intermediate-risk (n = 369), and high-risk groups (n = 116) accordingly. There was no difference in OS between patients in the BCLC staging and patients in low-risk group (P = 0.996). However, OS was significantly different between patients in the BCLC staging and those in intermediate-risk (P = 0.003) and high-risk groups (P < 0.001). Conclusion: IPLRs in the BCLC staging system have better prognosis. However, IPLRs in the HKLC staging system but beyond the BCLC staging may have equivalent prognosis to IPLRs in the BCLC staging if the tumor size is ≤ 5 cm and liver cirrhosis is absent.

Single-Cell RNA Sequencing Reveals the Interaction of Injected ADSCs with Lung-Originated Cells in Mouse Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a severe chronic lung disease with little effective treatment options other than lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using bleomycin- (BLM-) induced mice PF model and green fluorescent protein- (GFP-) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell RNA sequencing (scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR, ANNEXIN, HGF, and PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2 + antiinflammatory lung macrophages and lowered further inflammation and fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better therapeutic effects in PF.

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy. METHODS: HepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR. RESULTS: In this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR. CONCLUSION: This study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

Tumor enhancement ratio with unenhanced imaging is an independent prognostic factor for patients with hepatocellular carcinoma after transarterial chemoembolization.

OBJECTIVE: To investigative whether the odds tumor enhancement ratio (OTER) on cross-sectional imaging is a prognostic factor for hepatocellular carcinoma after transarterial chemoembolization (TACE). METHODS: This study involved 126 patients who underwent TACE from May 2015 to March 2019. The signal intensity/Hounsfield units (HU) was measured by placing regions of interest on the tumor and surrounding liver in unenhanced and arterial-phase contrast-enhanced cross-sectional images. The OTER was calculated as follows: OTER = (HUTUMORart - HUTUMORun)/ (HULIVERart - HULIVERun). Univariate analysis was performed to determine the factors associated with overall survival (OS). Variables with a P value of <0.10 were included in the multivariate Cox regression analysis. RESULTS: The median OS was 757 days. Tumors with a peripheral location, small size, and low OTER had better OS than those with a central location, large size, and high OTER. OS did not differ according to the extent of tumor involvement or tumor enhancement pattern. The OTER, tumor location, and size were included in the multivariate Cox regression analysis. A low OTER was the predictor of better OS. CONCLUSION: A high OTER is a risk factor for poor OS in patients undergoing TACE. This should be taken into consideration before the procedure.

Chemoembolization Plus Microwave Ablation vs Chemoembolization Alone in Unresectable Hepatocellular Carcinoma Beyond the Milan Criteria: A Propensity Scoring Matching Study.

PURPOSE: Transarterial chemoembolization (TACE) is recommended in patients with unresectable HCC beyond the Milan criteria (MC). However, the long-term efficacy of TACE remains unsatisfactory. Percutaneous microwave ablation (MWA) is a curative therapy for early-stage HCC that provides better local tumor control than TACE; however, MWA is limited for large or multifocal lesions. We aimed to compare treatment efficacy and downstaging rate following combined TACE-MWA and TACE alone in patients with unresectable HCC beyond the MC. PATIENTS AND METHODS: Patients with unresectable HCC beyond the MC who underwent either TACE-MWA (n=91) or TACE alone (n=140) at four medical institutions were included. Potential influencing factors on overall survival (OS) and progression-free survival (PFS) were included in the Cox regression analysis. Propensity-score matching of patients treated with TACE-MWA and TACE alone was performed. Differences in OS and PFS were compared with the Log rank test. Patients who met the University of California, San Francisco criteria were eligible for assessment of the probability of downstaging within the MC. Downstaging rate was compared between the two groups. RESULTS: In multivariate analysis, treatment with TACE alone was an independent predictor of poor PFS (P=0.011) and OS (P<0.001). Both PFS (P=0.043) and OS (P=0.002) were significantly higher in patients treated with TACE-MWA than those treated with TACE alone. The downstaging rate was higher in patients treated with TACE-MWA than those treated with TACE alone (P=0.039). CONCLUSION: Compared with TACE alone, TACE-MWA may offer a survival benefit in terms of OS and PFS in HCC patients beyond the MC. Additionally, TACE-MWA may provide higher probability of downstaging within the MC than TACE alone, thereby increasing the possibility of liver transplantation.

Predicting early refractoriness of transarterial chemoembolization in patients with hepatocellular carcinoma using a random forest algorithm: A pilot study.

Purpose: To develop and validate a random forest (RF) based predictive model of early refractoriness to transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: A total of 227 patients with unresectable HCC who initially treated with TACE from three independent institutions were retrospectively included. Following a random split, 158 patients (70%) were assigned to a training cohort and the remaining 69 patients (30%) were assigned to a validation cohort. The process of variables selection was based on the importance variable scores generated by RF algorithm. A RF predictive model incorporating the selected variables was developed, and five-fold cross-validation was performed. The discrimination and calibration of the RF model were measured by a receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test. Results: The potential variables selected by RF algorithm for developing predictive model of early TACE refractoriness included patients' age, number of tumors, tumor distribution, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR). The results showed that the RF predictive model had good discrimination ability, with an area under curve (AUC) of 0.863 in the training cohort and 0.767 in the validation cohort, respectively. In Hosmer-Lemeshow test, the RF model had a satisfactory calibration with P values of 0.538 and 0.068 in training cohort and validation cohort, respectively. Conclusion: The RF algorithm-based model has a good predictive performance in the prediction of early TACE refractoriness, which may easily be deployed in clinical routine and help to determine the optimal patient of care.

Intestinal microbiota participates in nonalcoholic fatty liver disease progression by affecting intestinal homeostasis.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a pathogenesis that has not been fully elucidated. With the development of the theory of the gut-liver axis and the deepening of related research, the role of the intestinal tract in the pathogenesis of NAFLD has been investigated more. Intestinal microbiota, intestinal metabolites, and intestinal epithelial and immune-based barriers constitute the intestinal environment, which uses crosstalk to maintain the homeostasis of the intestinal environment. This paper reviews the progress in the study of intestinal microbiota, intestinal environment, and NAFLD and suggests that repair of intestinal functional balance may be a new idea for early prevention and intervention of NAFLD.

Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

Systemic Inflammation Response Index is a Prognostic Risk Factor in Patients with Hepatocellular Carcinoma Undergoing TACE.

BACKGROUND: Mounting evidence has shown that systemic inflammation response index (SIRI), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil and monocyte counts, is associated with poor prognosis for several tumors. However, the prognostic value of SIRI in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is elusive. Herein, we aimed to evaluate the correlation between SIRI and clinical outcomes in these patients. METHODS: A total of 194 consecutive patients who underwent TACE were included in this study. Patients were stratified into high and low SIRI groups based on the cut-off value using receiver operating characteristic (ROC) analysis. Independent risk factors for tumor response were analyzed using forward stepwise logistic regression. A one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) and overall survival (OS) between low and high SIRI patients. The discriminatory power of the combination of number of tumors and SIRI in predicting initial TACE response was evaluated by ROC analysis. RESULTS: Patients were divided into high SIRI (> 0.88) and low SIRI (≤ 0.88) groups. High SIRI (p = 0.003) and more than three tumors (p = 0.002) were significantly related to poorer tumor response. Moreover, the low SIRI group had longer PFS and OS than the high SIRI group (both P < 0.05) before and after PSM. Combination of SIRI and number of tumors can improve the predictive ability to predict initial TACE response with an area under the curve (AUC) of 0.678. CONCLUSION: Pretreatment peripheral blood SIRI was found to be an independent predictor of tumor response and clinical outcomes in patients with HCC undergoing TACE. Patients with high SIRI may have a poor prognosis.

Effectiveness of sharp recanalization of superior vena cava-right atrium junction occlusion.

BACKGROUND: Conventional recanalization techniques may fail in patients with completely occluded superior vena cava (SVC). AIM: To analyze the effectiveness and complications of sharp recanalization for completely occluded SVC. METHODS: This was a retrospective study of patients that underwent puncture and recanalization of the SVC between January 2016 and December 2017 at our hospital. Sharp recanalization was performed using the RUPS-100 system. The patients were followed for 12 mo. The main outcomes were the patency rate of SVC and arteriovenous fistula flow during dialysis. RESULTS: The procedure was successful in all 14 patients (100%). Blood pressure in the distal SVC decreased in all 14 cases (100%) from 26.4 ± 2.7 cmH2O to 14.7 ± 1.3 cmH2O (P < 0.05). The first patency rates of the SVC at 24 h and at 3, 6, 9 and 12 mo after sharp recanalization were 100%, 92.9%, 85.7%, 78.6% and 71.4%, respectively. There were two (14.3%) severe, one (7.1%) moderate and one (7.1%) minor complication. The severe complications included one case of pericardial tamponade and one case of hemothorax. CONCLUSION: The results suggest that sharp recanalization can be an additional tool to extend or renew the use of an occluded upper extremity access for hemodialysis. This could be of use in patients with long-term maintenance hemodialysis in whom the maintenance of central venous access is often a challenge.

Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

Objectives: To develop and validate a predictive model for early refractoriness of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: In this multicenter retrospective study, a total of 204 consecutive patients who initially underwent TACE were included. Early TACE refractoriness was defined as patients presented with TACE refractoriness after initial two consecutive TACE procedures. Of all patients, 147 patients (approximately 70%) were assigned to a training set, and the remaining 57 patients (approximately 30%) were assigned to a validation set. Predictive model was established using forward stepwise logistic regression and nomogram. Based on factors selected by logistic regression, a one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) between patients who were present or absent of early TACE refractoriness. PFS curve was estimated by Kaplan-Meier method and compared by log-rank test. Results: Logistic regression revealed that bilobar tumor distribution (p = 0.002), more than three tumors (p = 0.005) and beyond up-to-seven criteria (p = 0.001) were significantly related to early TACE refractoriness. The discriminative abilities, as determined by the area under the receiver operating characteristic (ROC) curve, were 0.788 in the training cohort and 0.706 in the validation cohort. After PSM, the result showed that patients who were absent of early TACE refractoriness had a significantly higher PFS rate than those of patients who were present (p < 0.001). Conclusion: This study presents a predictive model with moderate accuracy to identify patients with high risk of early TACE refractoriness, and patients with early TACE refractoriness may have a poor prognosis.

Integrated Liver Inflammatory Score Predicts the Therapeutic Outcome of Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization.

PURPOSE: To evaluate the performance of the integrated liver inflammatory score (ILIS) in predicting survival in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization, and to compare ILIS to other prognostic scoring systems and inflammatory indices. MATERIALS AND METHODS: This study included 192 patients with unresectable HCC who underwent transarterial chemoembolization from 3 medical centers. The potential risk factors of the patients' overall survival (OS) were determined by multivariate Cox regression analysis. The predictive performances of ILIS in 1-, 2-, 3-, 4-, and 5-year survival were evaluated using receiver operating characteristic curves. The discriminatory power in the OS of ILIS and the other known scoring systems or inflammatory indices was determined by C-statistic. RESULTS: Multivariate regression analysis showed that high ILIS (P = .047), low lymphocyte count (P = .034), beyond up-to-seven criteria (P = .021), and nonresponse to the first transarterial chemoembolization session (P = .039) were risk factors for poor prognosis after transarterial chemoembolization. The predictive performances of ILIS for 1-, 2-, 3-, 4-, and 5-year survival were good, with area under the curve values of 0.627, 0.631, 0.621, 0.577, and 0.681, respectively. ILIS outperformed other standard scoring systems and inflammatory indices in predicting OS, with a C-statistic of 0.625. CONCLUSIONS: ILIS is a powerful prognostic index for predicting the survival of patients with HCC after transarterial chemoembolization, which suggests that ILIS before treatment should be considered during the patient evaluation process.

Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION: The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel syndrome based on single-cell sequencing technology.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

Clinical efficacy of Qi Di laxative decoction in the treatment of functional constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Functional constipation (FC) is a common gastrointestinal disorder characterized by slow bowel movement and defecation difficulties, significantly impacting patients' quality of life and exerting heavy financial burden to whole society. However, more than 50% FC patients are not completely satisfied with current therapies and alternative therapies are urgently required. Increasing evidences have demonstrated that traditional Chinese medicine has a good therapeutic effect on FC, which is well known for its multitarget and multimode effects on diverse diseases as well as less side effects. Furthermore, studies proved that Qi Di Laxative Decoction was an effective treatment for FC. Its safety and effectiveness should be verified by further studies. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the clinical efficacy of Qi Di Laxative Decoction in treating FC: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to November 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the clinical efficacy of Qi Di Laxative Decoction for patients with FC. The outcomes will include changes in FC relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the clinical efficacy of Qi Di Laxative Decoction in treating FC. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/M2ESR.

Identification of differentially expressed genes in ulcerative colitis and verification in a colitis mouse model by bioinformatics analyses.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease that is difficult to diagnose and treat. To date, the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators, such as C-reactive protein and the erythrocyte sedimentation rate, but these indicators have an unsatisfactory specificity. In this study, we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) databases and verified the selected core genes in a mouse model of dextran sulfate sodium (DSS)-induced colitis. AIM: To identify UC-related differentially expressed genes (DEGs) using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC. METHODS: Two microarray datasets from the NCBI-GEO database were used, and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams. We annotated these genes based on their functions and signaling pathways, and then protein-protein interactions (PPIs) were identified using the Search Tool for the Retrieval of Interacting Genes. The data were further analyzed with Cytoscape software and the Molecular Complex Detection (MCODE) app. The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed. Finally, colitis model mice were established by administering DSS, and the top three core genes were verified in colitis mice using real-time polymerase chain reaction (PCR). RESULTS: One hundred and seventy-seven DEGs, 118 upregulated and 59 downregulated, were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways. Seven clusters with close interactions in UC formed: Seventeen core genes were upregulated [C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine receptor 2 (CXCR2), CXCL9, CXCL5, C-C motif chemokine ligand 18, interleukin 1 beta, matrix metallopeptidase 9, CXCL3, formyl peptide receptor 1, complement component 3, CXCL8, CXCL1, CXCL10, CXCL2, CXCL6, CXCL11 and hydroxycarboxylic acid receptor 3] and one was downregulated [neuropeptide Y receptor Y1 (NYP1R)] in the top cluster according to the PPI and MCODE analyses. These genes were substantially enriched in the cytokine-cytokine receptor interaction and chemokine signaling pathways. The top three core genes (CXCL13, NYP1R, and CXCR2) were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice, but only CXCR2 expression was significantly different. CONCLUSION: Core DEGs identified in UC are related to inflammation and immunity inflammation, indicating that these reactions are core features of the pathogenesis of UC. CXCR2 may reflect the degree of inflammation in patients with UC.