OBJECTIVE: To evaluate the diagnostic accuracy of a dual-source computed tomography (DSCT) coronary angiography, with a particular focus on the effect of heart rate and calcifications. MATERIALS AND METHODS:One hundred and nine patients with suspected coronary disease were divided into 2 groups according to a mean heart rate (< 70 bpm and > or = 70 bpm) and into 3 groups according to the mean Agatston calcium scores (< or = 100, 101-400, and > 400). Next, the effect of heart rate and calcification on the accuracy of coronary artery stenosis detection was analyzed by using an invasive coronary angiography as a reference standard. Coronary segments of less than 1.5 mm in diameter in an American Heart Association (AHA) 15-segment model were independently assessed. RESULTS: The mean heart rate during the scan was 71.8 bpm, whereas the mean Agatston score was 226.5. Of the 1,588 segments examined, 1,533 (97%) were assessable. A total of 17 patients had calcium scores above 400 Agatston U, whereas 50 had heart rates > or = 70 bpm. Overall the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) for significant stenoses were: 95%, 91%, 65%, and 99% (by segment), respectively and 97%, 90%, 81%, and 91% (by artery), respectively (n = 475). Heart rate showed no significant impact on lesion detection; however, vessel calcification did show a significant impact on accuracy of assessment for coronary segments. The specificity, PPV and accuracy were 96%, 80%, and 96% (by segment), respectively for an Agatston score less than 100% and 99%, 96% and 98% (by artery). For an Agatston score of greater to or equal to 400 the specificity, PPV and accuracy were reduced to 79%, 55%, and 83% (by segment), respectively and to 79%, 69%, and 85% (by artery), respectively. CONCLUSION: The DSCT provides a high rate of accuracy for the detection of significant coronary artery disease, even in patients with high heart rates and evidence of coronary calcification. However, patients with severe coronary calcification (> 400 U) remain a challenge to diagnose.
Calcinosis/*radiography ; Coronary Angiography/methods/*standards ; Coronary Disease/*radiography ; Coronary Vessels/*pathology ; Female ; *Heart Rate ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; Tomography, X-Ray Computed/methods/*standards

Hepatocellular carcinoma(HCC)is a serious neoplastic disease with increasing incidence and mortality,accounting for 90%of all liver cancers.Hepatitis viruses are the major causative agents in the development of HCC.Hepatitis A virus(HAV)primarily causes acute infections,which is associated with HCC to a certain extent,as shown by clinicopathological studies.Chronic hepatitis B virus(HBV)or hepatitis C virus(HCV)infections lead to persistent liver inflammation and cirrhosis,disrupt multiple pathways associated with cellular apoptosis and proliferation,and are the most common viral precursors of HCC.Mutations in the HBV X protein(HBx)gene are closely associated with the incidence of HCC,while the expression of HCV core proteins contributes to hepatocellular lipid accumulation,thereby promoting tumorigenesis.In the clinical setting,hepatitis D virus(HDV)frequently co-infects with HBV,increasing the risk of chronic hepatitis.Hepatitis E virus(HEV)usually causes acute infections.However,chronic infections of HEV have been increasing recently,particularly in immuno-compromised patients and organ transplant recipients,which may increase the risk of progression to cirrhosis and the occurrence of HCC.Early detection,effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer,while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies.This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

Objective: To observe content of cytokine in human stromal vascular fraction gel (SVF-GEL) and effect of SVF-GEL on biological behaviors of epidermal and dermal cells in vitro and clinical efficacy of SVF-GEL. Methods: (1) SVF-GEL was prepared using liposuction aspirates harvested from females who received abdomen liposuction in author′s unit. SVF-GEL (1 mL) and high-glucose Dulbecco′s modified eagle medium (DMEM, 1 mL) were respectively cultured for 24 h with high-glucose DMEM containing 10% fetal calf serum, 10 g/L penicillin, and 10 g/L streptomycin, denoted as SVF-GEL group and negative control group, with 6 samples in each group. Content of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in the supernatant was determined by enzyme-linked immunosorbent assay. (2) A number of 5×10⁵ human skin fibroblasts (HSF) and HaCaT cells in logarithmic phase were inoculated and cultured in Transwell chambers for 12 h. All Transwell chambers containing cells were divided into SVF-GEL group (0.5 mL SVF-GEL was added for co-culture) and control group (0.5 mL high-glucose DMEM was added for co-culture), with 9 samples in each group for HSF and HaCaT cells. Scratch assay was performed after culture for 24 h, and residual scratch width was observed at post scratch hour (PSH) 0 (immediately), 24, and 48. Cell migration distance was measured at PSH 24 and 48. After culture for 24, 48, and 72 h, the number of living cell was counted using cell counter. (3) From June 2018 to June 2019, SVF-GEL was applied clinically to treat 15 patients with depressed scars on face, including 2 males and 13 females, aged 19 to 42 years. Survival condition of SVF-GEL and whether complications or not were observed 6 months after surgery. Before surgery and 6 months after surgery, depressed degree, color, and pliability of scar were compared. Vancouver Scar Scale (VSS) was employed to access color, vascularity, and pliability before surgery and 6 months after surgery, and total score was calculated. The number of patients with complete satisfaction or satisfaction was counted six months after surgery. Data were processed with analysis of variance of factorial design, paired samples t test, and Wilcoxon rank sum test. Results: (1) The content of EGF in SVF-GEL group and negative control group was (316.6±12.8) and (3.4±0.6) pg/mL, and the content of VEGF in SVF-GEL group and negative control group was (568.67±12.19) and (4.93±0.16) pg/mL, with statistically significant differences between the two groups (t=48.777, 92.485, P<0.01). (2) Residual scratch widths of HSF and HaCaT in SVF-GEL group and control group were decreased gradually along with time elapse, in which those in SVF-GEL group at PSH 24 and 48 were less than those in control group. At PSH 24 and 48, cell migration distances of HSF and HaCaT in SVF-GEL group were more than those in control group (t_HSF=-20.304, -43.516, t_HaCaT=-15.060, -8.684, P<0.01). After culture for 24, 48, and 72 h, the number of living cell of HSF and HaCaT in SVF-GEL group was significantly more than that in control group (t_HSF=-3.374, -6.809, -18.036, t_HaCaT=-4.793, -6.028, -8.141, P<0.05 or P<0.01). (3) Six months after surgery, SVF-GEL grafted into patients survived well without complications, and depressed degree of scar ameliorated obviously with lightened pigmentation and softer texture as compared with before surgery. Compared with those before surgery, VSS scores of color, vascularity, and pliability, and total score of 15 patients with depressed scars on face were obviously decreased 6 months after surgery (Z=-2.06, -2.07, -2.07, t=-15.811, P<0.05 or P<0.01). One patient was satisfied with the clinical outcome, and the rest 14 patients were completely satisfied with the clinical outcomes. Conclusions SVF-GEL contains cytokines EGF and VEGF, which can enhance cell migration ability and proliferation ability of HSF and HaCaT cells and have obvious effects on depressed scars for clinical application.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.