Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4/NF-κB/IKKα and JAK2/STAT3 signaling pathways.

OBJECTIVE: Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ's cardio-protection during sepsis and the mechanisms. METHODS: In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue. RESULTS: The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1ß, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group (p<0.05). TUNEL staining's results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl (p <0.05). CONCLUSIONS: In here, we observed that XBJ's cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.

Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report and review of the literature.

RATIONALE: Presence of synchronous double hepatocelluar carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (sdpHCC-ICC) located separately within a single liver is extremely rare. The purpose of this study is to investigate the clinical, imaging, pathological characteristics, and prognosis of patients with sdpHCC-ICC, in order to enhance our understanding of the disease and improve diagnostic and therapeutic effect. PATIENT CONCERNS: A 49-year-old, female with the diagnosis of hepatitis B virus with obvious liver cirrhosis, was admitted to our hospital. On admission, the levels of α-fetoprotein and carbohydrate antigen 19-9 were found to be elevated. Abdominal ultrasonography and enhanced computed tomography revealed 2 solid masses located in segments (S) 4 and 6 of the liver, with malignant behaviors. DIAGNOSES: In the light of above investigations, preoperative diagnosis of multiple primary hepatocellular carcinomas was made. INTERVENTION: Hepatic resection of both segments was done. The resected specimens revealed the presence of well-defined tumors in segments 4 and 6 measuring 5.0 cm and 2.5 cm respectively. OUTCOMES: Histopathological examination confirmed the tumor of the 4th segment to be moderately and poorly differentiated ICC, and the tumor of the 6th segment to be poorly differentiated HCC. Immunohistochemically, the ICC in S4 was positive for CK19 and negative for Heppar-1, whereas the HCC in S6 was positive for Heppar-1 and negative for CK19. Unfortunately, metastasis to multiple organs and lymph nodes were observed 3 months later. The patient died of liver failure 16 months after surgery. LESSONS: The clinical characteristics of sdpHCC-ICC are usually atypical and nonspecific making its preoperative diagnosis quite difficult. Hepatitis B virus and hepatitis C virus infection were both the independent risk factor for the development of sdpHCC-ICC. In patients with chronic liver disease, careful observation with imaging is of utmost necessity. Tumor markers may also play a valuable role in the diagnosis. The definite diagnosis depends on pathological examination. Hepatic resection is considered the most effective mode of treatment. The prognosis of synchronous occurrence of double hepatic cancers is worse than either HCC or ICC, and the origin of the disease needs further study.

The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma.

ABSTRACT: The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan-Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867-5.198] and pathological grades (OR = 1.437, 95% CI: 1.042-1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.

Whole-lesion histogram analysis metrics of the apparent diffusion coefficient: a correlation study with histological grade of hepatocellular carcinoma.

PURPOSE: The study evaluated the relationship between the histological grade of hepatocellular carcinoma (HCC) and the histogram-derived parameters of apparent diffusion coefficient (ADC) obtained from the whole-lesion assessment of diffusion-weighted magnetic resonance (MR) imaging in the liver. METHODS: A total of 51 patients were included. The parameters were correlated with the Edmondson-Steiner grades by using the Spearman correlation coefficient (ρ). The differences of ADC parameters between different tumor histological grades were compared using the Mann-Whitney U test. The extent to which each parameter aided in differentiating tumors with poor performance (III, IV) and fair performance (I, II) was assessed by using the area under the receiver operating characteristic curve (Az). RESULTS: The 25th percentile ADC exhibits the most negative correlation with histological grade (ρ = - 0.397), followed by the 30th percentile ADC (ρ = - 0.395), the minimum ADC value (ρ = - 0.390) and the 20th percentile ADC (ρ = - 0.385), whereas the minimum ADC value yielded the highest Az (0.763) in the discrimination of tumor foci with poor differentiation from fairly differentiated HCCs. The minimum ADC of 4.15 × 10-3 mm2/s or lower was considered to indicate poorly differentiated performance, and the corresponding sensitivity and specificity were 66.7 and 90.9%, respectively. CONCLUSION: The 25th percentile ADC showed a stronger correlation with the histological grade of HCC than other ADC parameters, and the minimum ADC value might be an optimal metric for determining poor and fair differentiations of HCC in DWI.

Synergistic antioxidant activities of eight traditional Chinese herb pairs.

Many Chinese therapeutic herbs that are traditionally used in combination demonstrate significantly better pharmacological effects when used in the combination than when used alone. However, the pharmacological mechanism for this synergism is still not well understood. In the present study, the antioxidant activities of six herbs ((Paeonia lactiflora (PL), Atractylodes macrocephala (AMA), Angelica sinensis (AS), Astragalus membranaceus (AME), Glycyrrhiza uralensis (GU) and Rheum officinale (RO)), which were historically combined into eight traditional Chinese herb pairs (TCHPs) (AME-AS, AME-AMA, AME-RO, AME-GU, AME-PL, PL-AS, PL-AMA and PL-GU), were investigated in vitro by assessing the 1,1-diphenyl-2-picryl hydrazine (DPPH)-radical scavenging abilities of the herbs. The results of this study showed that all eight TCHPs had a significantly larger scavenging capacity than would be expected from the theoretical sum of those of the respective constituent herbs (p<0.05). Furthermore, the AME-GU, AME-PL and AME-AMA pairs not only showed a significant synergistic effect in the DPPH scavenging assay, but they also demonstrated similar results in hydroxyl radical and superoxide radical anion scavenging assays. Interestingly, the AME-AMA combination had a significantly higher superoxide anion (0.2 g/ml) and hydroxyl radical scavenging ability than the AME or AMA. The changes in the total phenolic and flavonoid contents were also investigated. Our study showed a significant correlation between the rate of enhancement in antioxidant capacity and the rate of increase in flavonoid content. Thus, the flavonoids are likely responsible for the synergistic effects present in TCHPs.