mTOR inhibitor reduces nontumour-related death in liver transplantation for hepatocellular carcinoma.

Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18-1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08-0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.

Advance of Metformin in Liver Disease.

Metformin is a first-line drug for the treatment of type 2 diabetes with a good safety profile and relatively low cost. In recent years, many other effects of metformin have been discovered. In this review, we provide the research advances in metformin in liver disease. High-dose metformin can activate AMPK by inhibiting mitochondrial complex 1. In addition, low-dose metformin could activate lysosomal AMPK through PEN2. Activated AMPK can reduce fatty acid synthesis, inhibit tumor proliferation and metastasis, and reshape the tumor microenvironment. In addition, metformin can reduce ROS production by inhibiting mitochondrial complex 1, which can reduce liver damage. Therefore, metformin has been found to alleviate nonalcoholic fatty liver disease and cirrhosis, relieve liver damage, and reduce the incidence of hepatocellular carcinoma and cholangiocarcinoma. This information suggests that metformin may represent a new possibility for the prevention and treatment of liver diseases.

A Predictive Model of New-Onset Atrial Fibrillation After Percutaneous Coronary Intervention in Acute Myocardial Infarction Based on the Lymphocyte to C-Reactive Protein Ratio.

Purpose: Lymphocyte to C-reactive protein ratio (LCR) is a recognized systemic inflammatory marker and novel prognostic indicator for several cancers. This study investigated the relationship between preoperative LCR and new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Patients and Methods: Patients with AMI (n=662) with no history of atrial fibrillation (AF) were enrolled and classified into NOAF and non-NOAF groups based on the occurrence of postoperative NOAF during hospitalization. Logistic regression models were used to analyze NOAF risk factors and to assess the association between preoperative LCR and NOAF incidence. We constructed a new nomogram from the selected NOAF risk factors, and tested its predictive performance, degree of calibration, and clinical utility using receiver operating characteristic and calibration curves, decision curve analysis, and clinical impact curves. Results: Overall, 84 (12.7%) patients developed NOAF during hospitalization. The LCR was significantly lower in the NOAF group. Preoperative LCR accurately predicted NOAF after AMI and was correlated with increased NOAF risk. Age, body mass index, diabetes, serum albumin levels, uric acid levels, left atrium (LA) diameter, left ventricular ejection fraction, left circumflex artery stenosis > 50%, and Killip class II status were independent predictors of NOAF after AMI. In addition, a new nomogram combined with LCR was constructed to stratify the risk of NOAF in patients with AMI. The performance of the new nomogram was satisfactory, as shown by the receiver operating characteristic curve, calibration curve, decision curve analysis and clinical impact curve. Conclusion: Preoperative LCR was an independent predictor of NOAF in patients with AMI after PCI. The novel nomogram combined with LCR could rapidly and individually identify and treat patients at a high risk of NOAF.

TP53/mTORC1-mediated bidirectional regulation of PD-L1 modulates immune evasion in hepatocellular carcinoma.

BACKGROUND: Immunotherapy has facilitated great breakthroughs in the treatment of hepatocellular carcinoma (HCC). However, the efficacy and response rate of immunotherapy are limited and vary among different patients with HCC. TP53 mutation substantially affects the expression of immune checkpoint molecules in multiple cancers. However, the regulatory relationship between programmed death ligand 1 (PD-L1) and TP53 is poorly studied in HCC. We aimed to elucidate the regulatory mechanism of PD-L1 in HCC with different TP53 statuses and to assess its role in modulating immune evasion in HCC. METHODS: HCC mouse models and cell lines with different TP53 statuses were constructed. PD-L1 levels were detected by PCR, western blotting and flow cytometry. RNA-seqencing, immunoprecipitation, chromatin immunoprecipitation and transmission electron microscopy were used to elucidate the regulatory mechanism in HCC with different TP53 status. HCC mouse models and patient with HCC samples were analyzed to demonstrate the preclinical and clinical significance of the findings. RESULTS: We report that loss of p53 promoted PD-L1 expression and reduced CD8+ T-cell infiltration in patient with HCC samples and mouse models. Mammalian target of rapamycin (mTOR) pathway was activated in p53-loss-of-function HCC or after knocking down TP53. The transcription factor E2F1 was found to bind to the p53 protein in TP53 wild-type HCC cells, and inhibiting mammalian target of rapamycin complex 1 (mTORC1) disrupted this binding and enhanced E2F1 translocation to the nucleus, where it bound to the PD-L1 promoter and transcriptionally upregulated PD-L1. In p53-loss-of-function HCC cells, autophagosomes were activated after mTORC1 suppression, promoting the degradation of PD-L1 protein. The combination of mTOR inhibitor and anti-PD-L1 antibody enhanced CD8+ T-cell infiltration and tumor suppression in TP53 wild-type HCC mouse models, but no benefit was observed in p53-loss-of-function HCC mouse models. In patients with TP53 wild-type HCC, PD-L1 levels were significantly higher in the high E2F1 group than in the low E2F1 group, and the low E2F1 level group had significantly superior survival. CONCLUSION: We revealed the bidirectional regulatory mechanism of PD-L1 mediated by TP53/mTORC1 in HCC. The combination of mTOR inhibitor and anti-PD-L1 antibody could be a novel precise immunotherapy scheme for TP53 wild-type HCC.

Predictive value of CT-based extracellular volume fraction in the preoperative pathologic grading of rectal adenocarcinoma: A preliminary study.

OBJECTIVE: This study aimed to investigate whether the extracellular volume fraction (ECV) determined using enhanced computed tomography (CT) can predict the pathologic grade of rectal adenocarcinoma. METHODS: We prospectively analyzed 43 patients with rectal adenocarcinoma confirmed surgically and pathologically and who had undergone preoperative enhanced CT imaging. The plain, arterial, venous, and balance phase values were recorded, and the absolute contrast-enhanced CT differences ΔS1 = HUarterial phase-HUplain scan, ΔS2 = HUvenous phase-HUplain scan, ΔS3 = HUbalance phase-HUplain scan were obtained. The ECV of the primary lesion was calculated by measuring the CT values of the regions of interest in the plain and balance phases. Patients were allocated to either a low-grade or a high-grade group based on the histologic grading standard for colorectal adenocarcinoma (nonspecial type, World Health Organization 2010 standard). The differences in the parameters between the two groups were evaluated for statistical significance. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency. RESULTS: The 43 enrolled patients [12 in the high-grade group (27.9%) and 31 in the low-grade group (72.1%)] had an average age of 64.47 years. The arterial phase (P = 0.005) as well as ΔS1 (P = 0.006), ΔS3 (P = 0.021), and ECV (P＜ 0.001) differed significantly between the high-grade and low-grade groups, with ECV (P＜ 0.001) and ΔS3 (P = 0.042) being positively correlated with the pathologic grade and arterial phase (P = 0.025) and ΔS1 (P = 0.005) being negatively correlated. The ROC curve demonstrated that the best efficacy in evaluating the pathologic grade of rectal cancer was achieved by ECV, with an area under the curve of 0.892 (95% confidence interval: 0.757-1.000). The diagnostic threshold was 34.42%, sensitivity was 91.7%, and specificity was 83.9%. CONCLUSION: The use of enhanced CT to obtain ECV is helpful in predicting the pathologic grade of rectal cancer; however, this result has to be confirmed in a study with a larger sample size.

The predictive value of the modified AFP model for liver transplantation outcomes in multinodular hepatocellular carcinoma patients.

BACKGROUND: There is a lack of studies focusing on the benefit of liver transplantation (LT) in hepatocellular carcinoma (HCC) patients with > 3 tumors. This study aims to establish a model to effectively predict overall survival in Chinese HCC patients with multiple tumors (> 3 tumors) who undergo LT. METHODS: This retrospective study included 434 HCC liver transplant recipients from the China Liver Transplant Registry. All HCC patients had more than 3 tumor nodules. Three selection criteria systems (i.e., AFP, Metroticket 2.0, and Up-to-7) were compared regarding the prediction of HCC recurrence. The modified AFP model was established by univariate and multivariate competing risk analyses. RESULTS: The AFP score 2 and the AFP score ≥ 3 groups had 5-year recurrence rates of 19.6% and 40.5% in our cohort. The prediction of HCC recurrence based on the AFP model was associated with a c-statistic of 0.606, which was superior to the Up-to-7 and Metroticket 2.0 models. AFP level > 1000 ng/mL, largest tumor size ≥ 8 cm, vascular invasion, and MELD score ≥ 15 were associated with overall survival. The 5-year survival rate in the modified AFP score 0 group was 71.7%. CONCLUSIONS: The AFP model is superior in predicting tumor recurrence in HCC patients with > 3 tumors prior to LT. With the modified AFP model, patients likely to derive sufficient benefit from LT can be identified.

Comparative analysis of the liver-protective effects of raw and stir-fried semen of Hovenia dulcis in rats via gas chromatography-mass spectrometry-based serum metabolomic profiling and chemometrics.

In this study, we used a serum metabolomics methodology based on GC coupled with MS (GC-MS) to investigate the liver-protective effects of raw and stir-fried semen of Hovenia dulcis in rats models of carbon tetrachloride-induced liver injury. Multivariate statistical analysis, such as principal component analysis and orthogonal partial least squares discriminant analysis, were performed to examine changes in the metabolic state of rats with carbon tetrachloride-induced liver injury, as well as the recovery pattern of rats pretreated with the raw and stir-fried semen of H. dulcis. Liver tissues were subjected to histopathological examination. A total of 47 biomarkers were predicted to contribute to the dynamic pathological processes in the liver injury, such as phenylalanine, glutamic acid, glycine, arachidonic acid and linoleic acid. Further analysis revealed that pathways associated with phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism were altered in the injured liver, and that pretreatment with raw and stir-fried semen of H. dulcis abolished the changes in the aforementioned metabolic pathways.

Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus idaeus Linnaeus (RI) is a Chinese herbal medicine that has been widely used in China for a long time to reinforce the kidney, nourish the liver, improve vision, and arrest polyuria. AIM OF THE STUDY: This work aims to evaluate the recent progress of the chemical composition, pharmacological activity, pharmacokinetics, metabolism, and quality control and of Rubus idaeus, which focuses on the insufficiency of existing research and will shed light on future studies of Rubus idaeus. METHODS: Literatures about "Rubus idaeus","Red raspberry" and "Fupenzi"are retrieved by browsing the database, such as Web of Science (http://www.webofknowledge.com/wos), Pubmed (https://pubmed.ncbi.nlm.nih.gov/), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn). In addition, related textbooks and digital documents are interrogated to provide a holistic and critical review of the topic. The period of the literature covered from 1981 to 2022. RESULTS: Approximately 194 compounds have been isolated from Rubus idaeus, which is rich in phenols, terpenoids, alkaloids, steroids, and fatty acids. Numerous investigations have demonstrated that Rubus idaeus exhibits many pharmacological activities, including hypoglycemic and hypolipidemic, anti-Alzheimer effect, anti-osteoporosis, hepatoprotective, anti-cancer, neuroprotective, anti-bacteria and skin care, etc. However, it is worth noting that most of the research is not associated with the conventional effect, such as reducing urination and treating opacity of the cornea. CONCLUSION: The effectiveness of Rubus idaeus has been proved by its long-term clinical application. The research on the pharmacological activity of Rubus idaeus has flourished. In many pharmacological experiments, only the high-dose group can achieve the corresponding efficacy, so the efficacy of Rubus idaeus needs to be further interrogated. Meanwhile, the relationship between pharmacological activity and specific compounds of Rubus idaeus has not been clarified yet. Last but not least, studies involving toxicology and pharmacokinetics are very limited. Knowledge of bioavailability and toxicological behavior of Rubus idaeus can help understand the herb's pharmacodynamic and safety profile.

AC099850.3/NCAPG Axis Predicts Poor Prognosis and is Associated with Resistance to EGFR Tyrosine-Kinase Inhibitors in Lung Adenocarcinoma.

Background: TKI-acquired resistance markedly interferes with treatment of lung cancer patients with EGFR mutant features. Long non-coding RNAs (lncRNAs) modify EGFR-TKI resistance during tumor progression. Non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) is a mitosis-related protein that is involved in tumorigenesis. We investigated the potential regulatory lncRNAs of NCAPG in lung adenocarcinoma (LUAD) and assessed their roles in EGFR-TKI resistance. Methods: Data for 1678 lung cancer patients were retrieved from TCGA and GEO databases and used to evaluate NCAPG and lncRNAs expressions, as well as their prognostic significance in LUAD. Protein levels of NCAPG in LUAD were validated by immuno-histochemistry. To assess the relationship between NCAPG levels and EGFR-TKIs sensitivity, a cohort of 57 LUAD patients administered with EGFR-TKIs was used. Results: Both NCAPG and lncRNA AC099850.3 were over-expressed in LUAD tissues, and correlated with tumor progression and poor prognosis in LUAD. LncRNA AC099850.3 was identified as a potential regulator of NCAPG expressions. The AC099850.3/NCAGP axis was markedly correlated with EGFR mutations and IC50 of EGFR-TKIs. Besides, elevated NCAPG levels were associated with EGFR-TKIs resistance in 57 LUAD patients undergoing TKIs treatment. Gene set enrichment analysis revealed that both AC099850.3 and NCAGP were abundant in the cell cycle and the p53 signaling pathway. Conclusion: The AC099850.3/NCAPG axis is a potential prognostic predictor and therapeutic biomarker for EGFR-TKIs in LUAD.

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms.

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.

E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation.

The mammalian target of rapamycin (mTOR) pathway is frequently deregulated and has critical roles in cancer progression. mTOR inhibitor has been widely used in several kinds of cancers and is strongly recommended in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). However, the poor response to mTOR inhibitors due to resistance remains a challenge. Hypoxia-associated resistance limits the therapeutic efficacy of targeted drugs. The present study established models of HCC clinical samples and cell lines resistance to mTOR inhibitor sirolimus and screened out E2F7 as a candidate gene induced by hypoxia and promoting sirolimus resistance. E2F7 suppressed mTOR complex 1 via directly binding to the promoter of the TSC1 gene and stabilizes hypoxia-inducible factor-1α activating its downstream genes, which are responsible for E2F7-dependent mTOR inhibitor resistance. Clinically, low E2F7 expression could be an effective biomarker for recommending patients with HCC for anti-mTOR-based therapies after LT. Targeting E2F7 synergistically inhibited HCC growth with sirolimus in vivo. E2F7 is a promising target to reverse mTOR inhibition resistance. Collectively, our study points to a role for E2F7 in promoting mTOR inhibitor resistance in HCC and emphasizes its potential clinical significance in patients with HCC after LT.

Therapy response assessment of non-small cell lung cancer using dual-energy computed tomography iodine map.

OBJECTIVE: To investigate feasibility of the quantitative parameters of dual-energy computed tomography (DECT) to assess therapy response in advanced non-small cell lung cancer (NSCLC) compared with the traditional enhanced CT parameters based on the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. METHODS: Forty-five patients with unresectable locally advanced NSCLC who underwent DECT before and after chemotherapy or concurrent chemoradiotherapy (cCRT) were prospectively enrolled. By comparing baseline studies with follow-up, patients were divided into two groups according to RECIST guidelines as follows: disease control (DC, including partial response and stable disease) and progressive disease (PD). The diameter (D), attenuation, iodine concentration and normalized iodine concentration of arterial and venous phases (ICA, ICv, NICA, NICv) and the percentage of these changes pre- and post-therapy were measured and calculated. The Pearson correlation was used to analyze correlation between various quantitative parameters. The receiver operating characteristic (ROC) curves were used to evaluate accuracy of therapy response prediction. RESULTS: The change percentages of Attenuation (Δ-Attenuation-A and Δ-Attenuation-V), IC (ΔICA and ΔICV) and NIC (ΔNICA and ΔNICV) pre- and post-therapy correlate with the change percentage of D (ΔD). Among these, ΔICA strongly correlates with ΔD (r = 0.793, P < 0.001). The areas under ROC curves generated using Δ-Attenuation-A, ΔICA, and ΔNICA are 0.796, 0.900, and 0.880 with the corresponding cutoff value of 9.096, -15.692, and -4.7569, respectively, which are significantly different (P < 0.001). CONCLUSIONS: The quantitative parameters of DECT iodine map, especially iodine concentration, in arterial phase provides a new quantitative image marker to predict therapy response of patients diagnosed with advanced NSCLC.

Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis.

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.

Autophagy was involved in tumor necrosis factor-α-inhibited osteogenic differentiation of murine calvarial osteoblasts through Wnt/ß-catenin pathway.

Periodontitis is an inflammatory disease with a high incidence characterized by irreversible destruction of alveolar bone. This study aimed to investigate the effect of tumor necrosis factor-α (TNF-α) on osteogenic differentiation and its molecular mechanism. TNF-α inhibited osteogenic differentiation as revealed by the lower accumulation of osteoblastic genes like runt-related transcription factor (Runx2), alkaline phosphatase (ALP), osteoprotegerin (OPG), and osteocalcin (OCN). Moreover, TNF-α down-regulated the expressions of LC3II, ATG7, and beclin 1 (BECN1); suggesting that autophagy was inhibited during the process of osteogenic differentiation. Consistently, Wnt/ß-catenin signaling pathway members such as low-density lipoprotein receptor-related protein 5 (LRP5), ß-catenin, and phosphorylated-ß-catenin (p-ß-catenin) were reduced by TNF-α. Furthermore, the inhibitory effect of TNF-α on osteogenic differentiation and the Wnt/ß-catenin signaling pathway could be abated by autophagy inducers but exacerbated by autophagy inhibitors. The most intriguing finding of all was that TNF-α inhibited osteoblastic differentiation and the Wnt/ß-catenin signaling pathway by down-regulating autophagy, and autophagy positively regulated the Wnt/ß-catenin pathway and thus influenced osteoblastic differentiation. Our study provides a theoretical basis for autophagy-inducer therapy for the alveolar bone loss caused by periodontitis.

Autophagy negative-regulating Wnt signaling enhanced inflammatory osteoclastogenesis from Pre-OCs in vitro.

Periodontitis thereby the alveolar bone loss induced by inflammation, is a wide-spread phenomenon around the world. It is an ongoing challenge faced by clinicians worldwide. This study aimed to identify the effects of lipopolysaccharide (LPS) on osteoclasts (OCs) differentiation in vitro and to investigate its molecular mechanism. For bone marrow derived macrophages (considered as Pro-OCs), LPS impaired their differentiation into OCs in a dose-dependent manner. In contrast, it promoted Pre-OCs (referred to receptor activator of nuclear factor-κB ligand (RANKL) pretreated Pro-OCs) and differentiated to OCs with increased maximum diameter, quantity, the covering area and the fusion index in vitro. It also facilitated OCs proliferation, bone resorption and OCs related genes expression. Furthermore, it was revealed that LPS enhanced OCs genesis from Pre-OCs via activating autophagy pathway consequently elevated the accumulation of TRAP, Cts K and NFATC1, specific genes of OCs. The members of Wnt signaling were expressed as at lower states during the LPS induced OCs formation, but they could be rescued in the presence of autophagy inhibitor. The most promising observation was the direct interaction of LC3B and Dvl2, indicating that the crosstalk between above pathways existed in OCs. Taken together, we consider that LPS activates autophagy which negatively regulates Wnt signaling via autophagic degradation of Dvl2 is significant for osteoclastogenesis from Pre-OCs in vitro. Our study sheds light on the fact that autophagy inhibitors will become a new, potentially applicable therapeutic option in the treatment of periodontal bone loss.

CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B.

BACKGROUND: Immune inhibitory receptors play an important role in chronic infections. However, little is known about their role in hepatitis B virus (HBV) infection. Here, we analyzed the relationship between programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) expression on CD4+ T cells and HBV disease progression. RESULTS: PD-1 and LAG-3 expression was significantly higher on CD4+ T cells from HBV patients than on those from the HCs. In addition, a significant positive correlation was found between the PD-1 and LAG-3 expression levels and the ALT(alanine aminotransferase) level. CD4+ T cell function was inhibited by high PD-1 and LAG-3 levels, and CD4+ T cells with high PD-1 and LAG-3 expression lost the ability to secrete IFN-γ, IL-2 and TNF-α. Furthermore, blockade of the PD-1 and LAG-3 pathways reversed the damage to CD4+ T cell proliferation and cytokine secretion. CONCLUSIONS: CD4+ T cell exhaustion during chronic HBV had high PD-1 and LAG-3 expression and the absence of helper T cell cytokines, including IFN-γ, IL-2 and TNF-α. After blocking PD-L1 and LAG-3, CD4+ T cell function in chronic hepatitis B patients was partially restored.

Correlation Between Dual-Energy Computed Tomography Single Scan and Computed Tomography Perfusion for Pancreatic Cancer Patients: Initial Experience.

OBJECTIVE: The objective of this study was to evaluate the role and limit of iodine maps by dual-energy computed tomography (CT) single scan for pancreatic cancer. METHODS: Thirty patients with suspected solitary pancreatic cancer were enrolled in this study and underwent CT perfusion and iodine maps. The parameters of pancreatic cancer and normal pancreatic tissue were calculated. Pearson correlation and paired t test were used for evaluating 2 techniques. RESULTS: Iodine concentration had a moderate positive correlation with blood flow or blood volume (P < 0.05 for both). All values of iodine concentration and blood flow, iodine concentration, and blood volume had significant positive correlations (P < 0.001 for both). The mean effective dose for CT perfusion and iodine maps had significant difference (8.61 ± 0.00 mSv vs 1.13 ± 0.14 mSv, P < 0.001). CONCLUSIONS: Iodine maps had the potential to replace routine CT perfusion for pancreatic cancer with low radiation dose.