Xanthine oxidase inhibitory constituents from the roots of Ampelopsis japonica.

Bioassay-guided purification of the xanthine oxidase (XOD) inhibitory extract of the roots of Ampelopsis japonica resulted in the isolation of two new triterpenoids (1-2), designated Ampejaponoside A and B, along with sixteen known compounds (3-18). The structures of Ampejaposide A and B were elucidated by comprehensive analysis of spectroscopic data with the structures of the known compounds 3-18 confirmed by comparison the spectral data with corresponding values reported in literatures. All the isolates were evaluated for their XOD inhibitory activity in vitro. As a result, compounds 2, 8, and 14-16 displayed significant XOD inhibitory effect, particularly 16 being the most potent with an IC50 value of 0.21 µM, superior to positive substance allopurinol (IC50 1.95 µM). Molecular docking uncovered a unique interaction mode of 16 with the active site of XOD. The current study showed that the triterpenoids and polyphenols from A. japonica could serve as new lead compounds with the potential to speed up the development of novel XOD inhibitors with clinical potential to treat hyperuricaemia and gout.

Individualized Clinical Target Volume for Irradiation of the Supraclavicular Region in Breast Cancer Based on Mapping of the Involved Ipsilateral Supraclavicular Lymph Nodes.

PURPOSE: To map supraclavicular fossa-involved lymph nodes (SCF-LNs) in patients with nonmetastatic breast cancer, evaluate the coverage of widely adopted atlases, and propose modified borders for individualized regional irradiation. METHODS AND MATERIALS: M0 patients with biopsy-proven SCF-LNs who were SCF treatment-naïve were included. The SCF was spatially divided into subregions, with each node mapped on the original images. The geographic misses after the borders of multiple atlases were evaluated and factors affecting SCF-LNs' spread pattern were analyzed. RESULTS: From 1998 to 2022, 209 patients with 1242 SCF-LNs were eligible. Patients had a median of 4 nodes. At least 537 nodes (43.2%) in 147 patients (70.3%) were lateral to the sternocleidomastoid muscle (SCM), and 403 nodes (32.4%) in 127 patients (60.8%) were dorsal to the anterior scalene muscle (ASM). In the 88 patients with ≤3 SCF-LNs, at least 66 nodes (39.1%) in 40 patients (45.5%) were lateral to the SCM, and 34 nodes (20.1%) in 29 patients (33.0%) were dorsal to the ASM. These nodes were not covered by the Radiation Therapy Oncology Group (RTOG) atlas and partly within the Radiotherapy Comparative Effectiveness atlas. One hundred four patients (49.8%) had 432 SCF-LNs (34.8%) beyond the upper border of the European Society for Radiotherapy and Oncology (ESTRO) atlas. In multivariate regression, nodal sizes were associated with wider spread in the primary group. Being triple-negative (TN) subtype was associated with less spread in the recurrent group. Situation-based clinical target volumes (CTVs) were theorized, in which for a sequential spread, the posterior border could be the posterior scalene muscle or even be more constringent; otherwise, it should touch the anterior trapezius surface. CONCLUSIONS: SCF-LNs tend to spread laterally and dorsally beyond the RTOG borders, even in M0 stages with ≤3 SCF-LNs. The ESTRO upper border does not guarantee coverage with multiple SCF-LNs. Nodal burden and non-TN types are predictive of wider dissemination. A situation-based CTV is possibly feasible. Deciphering the SCF-LN spread route is needed.

Key pathways and genes in hepatitis B virus-related liver inflammation: Expression profiling and bioinformatics analysis.

Chronic hepatitis B virus infection has become a major public health issue worldwide, which can lead to liver inflammation, fibrosis, and hepatocellular carcinoma. According to the inflammation activity, liver tissues can be divided into 5 grades (G0-G4). However, the mechanism of the development of liver inflammation remains unclear. In our study, expression profiling by microarray and bioinformatics technology was used to systemically identify differentially expressed genes (DEGs) between low grades (G0-G1) and high (G2-G4) grades of liver inflammation. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network construction were performed for further identification of the key functions, pathways, and hub genes that might play important roles in the inflammation development. A total of 1982 DEGs were identified, consisting of 1220 downregulated genes and 762 upregulated genes. GO analysis revealed the DEGs were mainly enriched in GO terms that related to neutrophil activation and degranulation. MAPK1, ITGA2, CDK2, TGFB1, CDKN2A, MTOR, IL6, PCNA, OAS2, and EP300 were hub genes that had the highest centricity and might be potential markers for inflammation development. This study identified the differentially expressed genes between different grades of inflammation, which would enlighten the study that focuses on the mechanism of liver inflammation development.

Prognostic Value of Serum Apolipoprotein B to Apolipoprotein A-I Ratio in Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Propensity Score-Matched Analysis.

INTRODUCTION: The prognosis of advanced hepatocellular carcinoma (HCC) varies in patients receiving transcatheter arterial chemoembolization (TACE). In this study, we aimed to assess the prognostic value of serum apolipoprotein B (ApoB)/apolipoprotein A-I (ApoA-I) in this group of patients. METHODS: The serum lipid levels of HCC patients undergoing TACE were obtained from routine preoperative blood lipid examination. A propensity score-matched (PSM) analysis was used to eliminate the imbalance of baseline characteristics of the high and low ApoB/ApoA-I groups. Then, univariate and multivariate analysis were conducted to evaluate the prognostic value of ApoB/ApoA-I. RESULTS: In 455 HCC patients treated with TACE, ApoB/ApoA-I was positively correlated with AFP, T stage, distant metastasis, and TNM stage (p < 0.05). Patients with high ApoB/ApoA-I had a significantly shorter overall survival (OS) than those with low ApoB/ApoA-I (median OS, 21.7 vs. 39.6 months, p < 0.001). Multivariate analysis indicated that ApoB/ApoA-I was an independent prognostic index for OS (hazard ratio [HR] = 1.42, p = 0.008). After baseline characteristics were balanced, 288 patients were included in the PSM cohort. In this cohort, high ApoB/ApoA-I still predicted inferior OS in both univariate analysis (median OS, 27.6 vs. 39.3 months, p = 0.002) and multivariate analysis (HR = 1.58, p = 0.006). CONCLUSION: Serum ApoB/ApoA-I is a useful biomarker in predicting aggressive clinicopathological characteristics and poor prognosis in HCC patients treated with TACE.

Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion.

In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies.

Efficacy of cytokine-induced killer cell-based immunotherapy for hepatocellular carcinoma.

In attempts to delay tumor progression after surgery or minimally invasive local treatments, multidisciplinary strategies have been broadly studied in patients with hepatocellular carcinoma (HCC). The objective of this present study was to evaluate the efficacy of autologous transplantations of cytokine-induced killer (CIK) cells as an adjuvant therapy for patients with HCC. A total of 264 patients with HCC were enrolled in this retrospective study. Of these patients, 165 received either CIK cell therapy alone or as adjuvant therapy to surgery, transcatheter arterial chemoembolization (TACE), or TACE-based comprehensive treatments (CT). The remaining 99 patients received only surgery or TACE. Kaplan-Meier analysis and the Chi-squared test were used to analyze the overall survival (OS), progression-free survival (PFS), and clinical characteristics of the patients in the different treatment subgroups. Kaplan-Meier analysis suggested that patients in the Surgery+CIK group had a significantly improved OS compared with those in the other three groups (P < 0.001). Furthermore, patients who developed a fever after the CIK cell treatments manifested a likely better OS (P = 0.028). Subgroup analysis indicated that patients in the Surgery+CIK group likely had an improved PFS but a similar OS compared with the patients in the Surgery-alone group (P = 0.055 for PFS, and P = 0.746 for OS). Further subgroup analysis showed that the OS in both the TACE+CIK and CT+CIK groups was prolonged significantly compared with that in the TACE-alone group (P = 0.015 and P = 0.018, respectively). However, similar OS was observed between the TACE+CIK and CT+CIK groups (P = 0.686). Autologous transplantation of CIK cells as an adjuvant therapy was associated with better survival for patients with HCC, especially for those who had also undergone TACE. A fever reaction might be a potential event for assessing the curative effect of the CIK treatment.

The Prognostic Value of aspartate aminotransferase to lymphocyte ratio and systemic immune-inflammation index for Overall Survival of Hepatocellular Carcinoma Patients Treated with palliative Treatments.

Background: Lymphocytes were reported to play a significant part in host anticancer immune responses and influence tumour prognosis. Few studies have focused on the prognostic values of aspartate aminotransferase (AST) to lymphocyte ratio (ALRI), aspartate aminotransferase to platelet count ratio index (APRI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) treated with palliative treatments. Methods: Five hundred and ninety-eight HCC patients treated with palliative therapies were retrospectively analysed. We randomly assigned patients into the training cohort (429 patients) and the validation cohort I (169 patients). Receiver operating characteristic (ROC) curves were used to identify the best cut-off values for the ALRI, APRI and SII in the training cohort and the values were further validated in the validation cohort I. Correlations between ALRI and other clinicopathological factors were also analysed. A prognostic nomogram including ALRI was established. We validated the prognostic value of the ALRI, SII and APRI with two independent cohorts, the validation cohort II of 82 HCC patients treated with TACE and the validation cohort III of 150 HCC patients treated with curative resection. In the training cohort and all the validation cohorts, univariate analyses by the method of Kaplan-Meier and multivariate analysis by Cox proportional hazards regression model were carried out to identify the independent prognostic factors. Results: The threshold values of ALRI, APRI and SII were 86.3, 1.37 and 376.4 respectively identified by ROC curve analysis in the training cohort. Correlation analysis showed that ALRI>86.3 was greatly associated with higher rates of Child-Pugh B&C, portal vein tumor thrombosis (PVTT) and ascites (P < 0.05). Correspondingly, ALRI level of HCC patients with Child-Pugh B&C, PVTT and ascites was evidently higher than that of HCC patients with Child-Pugh A, without PVTT and without ascites (P < 0.001). In the training cohort and the validation cohort I, II, III, the OS of patients with ALRI >86.3 was obviously shorter than patients with ALRI ≤86.3 (P <0.001). We identified ALRI as an independent prognostic factor by univariate and multivariate analyses both in training Cohort (HR=1.481, P=0.004), validation cohort I (HR=1.511, P=0.032), validation cohort II (HR=3.166, P=0.005) and validation cohort III (HR=3.921, P=0.010). The SII was identified as an independent prognostic factor in training cohort (HR=1.356, P=0.020) and the validation cohort II (HR=2.678, P=0.002). The prognostic nomogram including ALRI was the best in predicting 3-month, 6-month, 1-year, 2-year survival And OS among TNM, ALRI, ALRI-TNM and nomogram. Conclusions: The ALRI was a novel independent prognostic index for the HCC patients treated with palliative treatments.

Cancer incidence in patients with type 2 diabetes mellitus: a population-based cohort study in Shanghai.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been suggested to increase the risk of cancers. The aim of this study was to investigate the risk of common cancers in Chinese patients with T2DM. METHODS: A population-based retrospective cohort study including 36,379 T2DM patients was conducted in Minhang District of Shanghai, China, during 2004 to 2010. All T2DM patients were enrolled from the standardized management system based on local electronic information system. Newly-diagnosed cancer cases were identified by record-linkage with the Shanghai Cancer Registry. Standardized incidence ratios (SIR) and 95% confidence interval (CI) were used to estimate the risk of cancers among T2DM patients. RESULTS: Overall crude incidence rate (CIR) of cancers was 955.21 per 105 person-years in men and 829.57 per 105 person-years in women. Increased risk of cancer was found in both gender, with an SIR being 1.28 (95% CI = 1.17-1.38) in men and 1.44 (95% CI =1.32-1.55) in women. Increased risk of colon (SIR = 1.97; 95% CI = 1.49 to 2.46), rectum (1.72; 1.23 to 2.21), prostate (2.87; 2.19 to 3.56), and bladder cancers (1.98, 1.28 to 2.68) were observed in men and elevated risk of colon (1.67; 1.25 to 2.08), breast (1.66; 1.38 to 1.95), and corpus uteri cancers (2.87; 2.03 to 3.71) were observed in women. CONCLUSIONS: Our results indicate that Chinese patients with T2DM may have an increased risk of some cancers, and the increase may vary by sub-sites of cancers.

[Combination of morphine with low-dose naloxone for intravenous patient-controlled analgesia].

OBJECTIVE: To compare the analgesic effect and side effects of morphine for intravenous patient-controlled analgesia (PCA) with or without low-dose naloxone after abdominal surgery. METHODS: Fifty-nine ASA I - II patients undergoing elective abdominal surgery were randomly divided into two groups: group morphine received postoperative PCA with 0.4 mg/ml morphine (a 1 mg bolus with a 5 min lockout), group naloxone received morphine 0.4 mg/ml with 6 microg/kg naloxone. Blood pressure, heart rate, respiratory rate, and pulse oxygen saturation were monitored. Visual analogue scale (VAS), nausea/vomiting, pruritus, sedation and consumption of morphine were recorded for 24 hours. RESULTS: VAS had no difference between group morphine and group naloxone, but group naloxone had significantly lower VAS for pain at rest or movement (beyond 4-8 h), and the incidence of nausea/vomiting significantly decreased in group naloxone (P < 0.05). No differences existed in pruritus, sedation, respiratory rate, and hemodynamic parameters between these two groups. The 24 hours postoperative morphine consumption was (36.6 +/- 13.5) mg in group naloxone and (43.7 +/- 14.6) mg in group morphine (P < 0.05). CONCLUSION: For morphine PCA, morphine with 6 microg/kg naloxone is effective in preventing some PCA morphinerelated side effects. Naloxone not only reduces postoperative morphine requirements but also improves the analgesic effect.