[Corrigendum] T7 peptide inhibits angiogenesis via downregulation of angiopoietin­2 and autophagy.

Following the publication of this article, an interested reader drew to the authors' attention that two pairs of protein bands featured in the western blots in Fig. 3A and 5D on p. 679 and 681 respectively appeared to be strikingly similar. After having re­examined their original data, the authors realized that Fig. 5D had been assembled incorrectly. The revised version of Fig. 5, now including the correct data for Fig. 5D, is shown on the next page. Note that the errors made in terms of assembling the data in Fig. 5 did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors regret that these errors went unnoticed prior to the publication of their article, are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish this corrigendum. They also apologize to the readership for any inconvenience caused. [Oncology Reports  33: 675­684, 2015; DOI: 10.3892/or.2014.3653].

Hepatic artery pseudoaneurysm: three case reports and literature review.

Laparoscopic surgery is extensively applied in the treatment of hepatobiliary diseases. Hepatic artery pseudoaneurysm (HAP) is a rare complication following hepatic biliary surgery through laparoscopy. The clinical manifestations of HAP are diverse and can be fatal. Given its severity, rapid assessment and management are crucial to ensuring a good prognosis. Here, we report three cases of HAP; two underwent laparoscopic surgery due to cholelithiasis, and another caused by trauma. The first case exhibited a pseudoaneurysm involving the distal portion of the right hepatic artery main trunk. The second patient had a pseudoaneurysm at the bifurcation of the left and right hepatic arteries. The third case involved a patient with a pseudoaneurysm involving a branch of the right hepatic artery. The main clinical manifestations of all three cases were bleeding from the biliary tract (the first two cases showed postoperative bleeding in the T-tube, while the third case exhibited gastrointestinal bleeding). The final diagnosis was obtained through digital subtraction angiography. The three patients underwent successful transcatheter arterial embolization operation and a follow-up revealed they were disease-free and alive. This article aims to highlight a rare complication of laparoscopic hepatobiliary surgery and share our experience in early diagnosis and treatment of HAP.

MC1R regulates T regulatory cell differentiation through metabolic reprogramming to promote colon cancer.

BACKGROUND: Until 2021, colon cancer was a leading cancer globally. Early detection improves outcomes; however, advanced cases still having poor prognosis. Therefore, an understanding of associated molecular mechanisms is crucial for developing new preventive and therapeutic strategies for colon cancer. METHODS: The TCGA database was analyzed to assess melanocortin 1receptor (MC1R) expression in colon cancer and its link with patient prognosis. Further, models and diverse experimental techniques were employed to investigate the impact of MC1R on colon cancer progression and its underlying mechanism was elucidated. RESULTS: In a follow-up study of clinical patients, the important role of MC1R was identified in the development of colon cancer. First, MC1R was expressed more highly in colon tumor tissues than in adjacent tissues. In addition, MC1R was associated with colon cancer prognosis, and higher expression of MC1R tended to predict a worse prognosis. This conclusion was verified in MC1R-/- mice, which showed a greater resistance to tumor growth than wild-type mice, as expected. Further investigation revealed a significant change in the portion of Tregs in MC1R-/- mice, while the portion of CD4 + and CD8 + T cells remained unchanged. The in vitro experiments revealed a weaker ability of the MC1R-/- T cells to differentiate into Tregs. Previous studies report that the functional integrity of Tregs is interwoven with cellular metabolism. Therefore, MC1R was deduced to regulate the differentiation of Tregs by reprogramming the metabolism. As expected, MC1R-/- T cells exhibited weaker mitochondrial function and a lower aerobic oxidation capacity. Concurrently, the MC1R-/- T cells had stronger limiting effects on colon cancer cells. According to these results, the MC1R inhibitor was hypothesized as a potential therapeutic agent to suppress colon cancer. The results showed that upon MC1R suppression, the tumors in the mice developed more slowly, and the mice survived longer, potentially providing a novel strategy to treat clinical colon cancer. CONCLUSION: By regulating Tregs differentiation, MC1R overexpression in colon cancer correlates with poor prognosis, while MC1R inhibition shows potential as a therapeutic approach to slow tumor growth and enhance survival.

A novel subunit vaccine based on Fiber1/2 knob domain provides full protection against fowl adenovirus serotype 4 and induces stronger immune responses than a Fiber2 subunit vaccine.

Outbreaks of hepatitis-hydropericardium syndrome (HHS) caused by fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry in China since 2015. However, commercially available vaccines against the FAdV-4 infection remain scarce. In our study, subunit vaccine candidates derived from the bacterially expressed recombinant Fiber1 knob domain and Fiber2 knob domain fusion protein (termed as Fiber1/2 knob subunit vaccine) and Fiber2 protein (termed as Fiber2 subunit vaccine) of the FAdV-4 SDSX strain were developed. Immunogenicity evaluation showed that the Fiber1/2 knob subunit vaccine induced the production of antibodies at 7 d postvaccination (dpv), earlier than the Fiber2 subunit vaccine. Moreover, the neutralizing antibody level of the Fiber1/2 subunit vaccine group was higher than the Fiber2 subunit vaccine group, showing significant differences at 14, 21, and 28 dpv. Immune protection test results revealed that both Fiber1/2 knob subunit and Fiber2 subunit vaccines could protect chickens from death against FAdV-4 challenge, although the weight of chickens in the Fiber1/2 knob subunit vaccine group decreased less. Furthermore, analysis of plasma Glutamic oxaloacetic transaminase (AST) and blood glutamic pyruvic transaminase (ALT) levels suggested that the Fiber1/2 subunit vaccine can significantly inhibit liver damage caused by FAdV-4 infection and is more effective in blocking the pathogenicity of FAdV-4 in target organs. In addition, the Fiber1/2 knob subunit vaccine further reduced the viral load in different tissues and virus shedding in chickens than the Fiber2 subunit vaccine. Overall, the Fiber1/2 knob subunit vaccine was more effective than the Fiber2 subunit vaccine. These findings lay the foundation for the development of more effective FAdV-4 subunit vaccines.

Leptin receptor Gln223Arg and Lys109Arg polymorphisms may be associated with HBV-related hepatocellular carcinoma risk: A system review and meta-analysis.

Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta-analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case-control researches consisting of 1323 cases and 1919 control cases were incorporated into meta-analysis. Researches indicated A-allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)-related HCC (mutant model, OR = 1.81, 95% CI = 1.36-2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32-1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV-related HCC (wild model, OR 0.59, 95%CI = 0.46-0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14-2.01, p = .005) as well as in those with HBV-related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49-3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23-2.26, p = .001). G-allele and AA genotype of rs1137101 might be in connection with boosted HBV-related HCC susceptibility, and wild-type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV-related HCC susceptibility. Such conclusions ought to be validated by larger and better-designed researches.

Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

Preoperative albumin-alkaline phosphatase ratio affects the prognosis of patients undergoing hepatocellular carcinoma surgery.

BACKGROUND: The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. OBJECTIVE: This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. METHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. RESULTS: The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P< 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p= 0.036) and RFS (HR = 0.70, 95% CI 0.53-0.92, p= 0.011). CONCLUSIONS: The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment.

Nitrogen Fixation by Benzene into Pyridine and Aniline in Water/Nitrogen Plasma.

We demonstrated direct conversion of benzene into pyridine and aniline, assisted through exact mass measurements (m/z 80.0494, 93.0574, and 94.0651, respectively), through the interaction of benzene with water/nitrogen vapor plasma produced by corona discharge. Systematic analysis using a series of isotopic standards indicated that formation of pyridine and aniline occurred through the reaction between neutral benzene and reactive N+(OH2)2 in water/nitrogen plasma; exact mass measurements of products and intermediates supported this hypothesis. As the proportion of water vapor in plasma increased over time, the reaction proceeded from exclusive formation of protonated pyridine to formation of protonated aniline as the main product; theoretical simulations indicated that the presence of water vapor promoted proton migration to elicit formation of protonated aniline. The reactions we discovered suggest a new mechanism for direct nitrogen fixation.

Sex Differences in the Impact of Metabolic Dysfunction-associated Fatty Liver Disease on the of Patients with Hepatocellular Carcinoma After Radical Resection.

Background: International experts have put forward a new definition for metabolic dysfunction-associated fatty liver disease (MAFLD). Nonetheless, sex differences in MAFLD function in hepatocellular carcinoma (HCC) survival is still unknown. Therefore, the current work focused on exploring the gender-specific association of MAFLD effect on prognosis after radical resection of liver cancer. Methods: The long-term prognostic outcomes of 642 HCC patients undergoing hepatectomy were analyzed retrospectively. To calculate overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier (KM) curve was plotted. Further, using Cox proportional model to explore the prognostic factors. Sensitivity analysis was performed using propensity score matching (PSM) to balance the confounding bias. Results: For MAFLD patients, median OS and RFS times were 6.8 years and 6.1 years, respectively, compared to 8.5 years and 2.9 years in non-MAFLD patients. KM curve shown that compare with non-MAFLD patients, MAFLD patients had a higher survival rate in men, but had a lower survival rate in women (P<0.05). Multivariate analysis showed that MAFLD was significantly risk factor with mortality in the female (HR = 5.177, 95%CI: 1.475-18.193). However, MAFLD was not related to RFS This correlation was consistent after PSM analysis. Conclusions: MAFLD can improve the mortality of women undergoing radical resection for liver cancer, which independently estimate disease prognosis but is not related to recurrence-free survival.

The relationship between metabolic dysfunction-associated fatty liver disease and the incidence rate of extrahepatic cancer.

Background: The associations between metabolic dysfunction-associated fatty liver disease (MAFLD) and cancer development, especially extrahepatic cancers, are unknown. The aims of the current study were to investigate the cancer incidence rates of MAFLD and analyze the associations between MAFLD and the development of cancers. Methods: This historical cohort study included participants who underwent ultrasonographic detection of hepatic steatosis at a tertiary hospital in China from January 2013 to October 2021. MAFLD was diagnosed in accordance with The International Expert Consensus Statement. Cox proportional hazards regression modeling was used to assess the associations between MAFLD and the development of cancers. Results: Of the 47,801 participants, 16,093 (33.7%) had MAFLD. During the total follow-up of 175,137 person-years (median 3.3 years), the cancer incidence rate in the MAFLD group was higher than that in the non-MAFLD group [473.5 vs. 255.1 per 100,000 person-years; incidence rate ratio 1.86; 95% confidence interval (CI) 1.57-2.19]. After adjustment for age, gender, smoking status, and alcohol status, MAFLD was moderately associated with cancers of the female reproductive system/organs (labium, uterus, cervix, and ovary) [hazard ratio (HR) 2.24; 95% CI 1.09-4.60], thyroid (HR 3.64; 95% CI 1.82-7.30), and bladder (HR 4.19; 95% CI 1.15-15.27) in the total study cohort. Conclusion: MAFLD was associated with the development of cancers of the female reproductive system/organs (labium, uterus, cervix, and ovary), thyroid, and bladder in the total study cohort.

Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency. Methods: The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated. Results: A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04-1.67, P = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96-2.10, P = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09-1.87, P = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01-2.57, P = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09-1.79, P = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models. Conclusion: Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.

Blood gene expression predicts intensive care unit admission in hospitalised patients with COVID-19.

Background: The COVID-19 pandemic has created pressure on healthcare systems worldwide. Tools that can stratify individuals according to prognosis could allow for more efficient allocation of healthcare resources and thus improved patient outcomes. It is currently unclear if blood gene expression signatures derived from patients at the point of admission to hospital could provide useful prognostic information. Methods: Gene expression of whole blood obtained at the point of admission from a cohort of 78 patients hospitalised with COVID-19 during the first wave was measured by high resolution RNA sequencing. Gene signatures predictive of admission to Intensive Care Unit were identified and tested using machine learning and topological data analysis, TopMD. Results: The best gene expression signature predictive of ICU admission was defined using topological data analysis with an accuracy: 0.72 and ROC AUC: 0.76. The gene signature was primarily based on differentially activated pathways controlling epidermal growth factor receptor (EGFR) presentation, Peroxisome proliferator-activated receptor alpha (PPAR-α) signalling and Transforming growth factor beta (TGF-ß) signalling. Conclusions: Gene expression signatures from blood taken at the point of admission to hospital predicted ICU admission of treatment naïve patients with COVID-19.

Predictors and Dynamic Nomogram to Determine the Individual Risk of Malignant Brain Edema After Endovascular Thrombectomy in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). METHODS: We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. RESULTS: MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell's concordance index) of 0.925 (95% confidence interval=0.890-0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of <1.5 and tolerances of >0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). CONCLUSIONS: Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.

Generation of Phenol and Molecular Hydrogen through Catalyst-Free C-H Activation of Benzene by Water Radical Cations.

Here, we report on the abundant formation of phenol and molecular hydrogen when benzene vapor was exposed to gas plasma generated by +5.5 kV corona discharge of water vapor in argon in the absence of oxygen. Systematic analysis using a series of isotopic standards (d6-benzene, D2O, and H218O) and benzene derivatives (mono-, di-, trichlorobenzene, and N,N-dimethylaniline) indicated that the formation of phenol occurred through the reaction between neutral benzene and the radical cation of water dimer, (H2O)2+•. A two-step reaction mechanism was proposed based on the results of experiments and DFT calculations: (1) the formation of (C6H6...H2O)+• intermediate through electrophilic addition; (2) the formation of C6H5OH+• through the release of H2 from the (C6H6...H2O)+• intermediate. Our findings offer a novel catalyst-free method to prepare phenol from benzene with phenol selectivity >90%.

Diagnostic Accuracy of Intraoperative Intact Parathyroid Hormone Monitoring for Surgical Outcomes of Secondary Hyperparathyroidism.

BACKGROUND Intraoperative intact parathyroid hormone (IO-iPTH) monitoring has not reached a consensus in predicting surgical outcomes of secondary hyperparathyroidism. Here, we explore the predictive effect of IO-iPTH monitoring on surgical outcomes of secondary hyperparathyroidism as a potentially effective standard. MATERIAL AND METHODS We enrolled 119 patients who underwent total parathyroidectomy with autotransplantation from January 2016 to August 2019. Intact parathyroid hormone (iPTH) levels were tested 1 day before surgery (iPTHpre), 10 min after glands resection (iPTH10min), and 1 and 7 days after the operation (iPTHd1, iPTHd7). According to iPTHpre levels, patients were divided into a <2000 pg/ml group and a ≥2000 pg/ml group, and the cutoff values were compared. In patients with successful parathyroidectomy, the value of iPTHpre minus iPTH10min (iPTHdec) and relative-iPTH10min were compared between groups. RESULTS Using cutoff values, the predictive criterion was defined as iPTH10min ≤314.5 pg/ml or relative-iPTH10min ≤12.4%. In the iPTHpre ≥2000 pg/ml group, iPTH10min had a higher predictive value (318 pg/ml vs 218 pg/ml) whereas relative-iPTH10min had a lower predictive value (12.1% vs 20.3%). In patients with successful PTX, the iPTHdec value of the iPTHpre ≥2000 pg/ml group was significantly higher than that of the <2000 pg/ml group. Additionally, the relative-iPTH10min was significantly lower in the ≥2000 pg/ml group than in the <2000 pg/ml group. CONCLUSIONS An intraoperative predictive criterion of iPTH10min ≤314.5 pg/ml or relative-iPTH10min ≤12.4% is associated with effectively predicting surgical success of secondary hyperparathyroidism. The predictive value is affected by iPTHpre level; therefore, a variable prediction standard based on iPTHpre levels shall be established.

Clinical stages of recurrent hepatocellular carcinoma: A retrospective cohort study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and has relatively high recurrence rates. Few studies have been published on the clinical stages of recurrent HCC. AIM: To assess the applicability of the Barcelona Clinic Liver Cancer (BCLC) staging for recurrent HCC and the need to establish clinical stage criteria for recurrent HCC. METHODS: The clinicopathological data of 81 patients with recurrent HCC who were admitted to the Hospital of Guangxi Zhuang Autonomous Region from January 2013 to December 2017 were collected. The patients were divided into three groups according to the BCLC staging system as follows: (1) Group A with BCLC stage A, 51 patients; (2) Group B with BCLC stage B, 14 patients; and (3) Group C with BCLC stage C, 16 patients. The median time to tumor recurrence and the median overall survival were compared. RESULTS: The median time to tumor recurrence in groups A, B, and C was 16 ± 1.5 mo, 10 ± 2.8 mo, and 6 ± 0.5 mo, respectively, with a statistically significant difference among them (χ 2 = 70.144, P < 0.05); no statistically significant difference was noted between group A and group B (χ 2 = 2.659, P > 0.05), although there were statistically significant differences between group A and group C and between group B and group C (χ 2 = 62.110, and 19.972, P < 0.05). The median overall survival in groups A, B, and C were 42 ± 5.1 mo, 22 ± 3.1 mo, and 13 ± 1.8 mo, respectively, with a statistically significant difference among them (χ 2 = 38.949, P < 0.05); there were statistically significant differences between group A and group B, group A and group C, and group B and group C (χ 2 = 9.577, 37.172, and 7.183, respectively; P < 0.05). CONCLUSION: There are different prognoses in recurrent HCC patients according to the BCLC staging. Therefore, BCLC staging is applicable to recurrent HCC and it is essential to formulate clinical stage criteria for recurrent HCC.

MicroRNA-22 inhibits cell growth and metastasis in breast cancer via targeting of SIRT1.

[This retracts the article DOI: 10.3892/etm.2017.4590.].

Targeting of the COX-2/PGE2 axis enhances the antitumor activity of T7 peptide in vitro and in vivo.

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3ß1 and αvß3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3ß1 and αvß3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3ß1 not αvß3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

Tissue-Specific Immunopathology in Fatal COVID-19.

Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.