ASGR1 is a promising target for lipid reduction in pigs with PON2 as its inhibitor.

Although the role of asialoglycoprotein receptor 1 (ASGR1) in lowering lipid levels is well established, recent studies indicate that ASGR1 inhibition can cause unexpected liver damage in pigs, raising a serious issue about whether ASGR1 can be a good target for treating ASCVD. Here, we utilized the CRISPR-Cas9 system to regenerate ASGR1-knockout pigs, who displayed decreased lipid profiles without observable liver damage. This was confirmed by the lower levels of serum ALT and AST, reduced expression of inflammation markers, and normal histological morphology. Also, we implemented immunoprecipitation combined with mass spectrometry (IP-MS) and discovered that paraoxonase-2 (PON2) can interact with and significantly degrade ASGR1 in a dose-dependent manner. This degradation reduced lipid levels in mice, accompanied by little inflammation. Our study highlights the effectiveness and safety of degrading ASGR1 to reduce lipid levels in pigs and provides a potential inhibitor of ASGR1.

Association between the systemic immune inflammation index and recurrence or metastasis after interventional therapy in patients with primary liver cancer- a retrospective cohort study.

Background: The systemic immune inflammation index has been used to evaluate the prognosis of patients with a variety of malignant tumors. However, studies were limited in primary liver cancer (PLC) patients. This study aimed to investigate the association between the systemic immune inflammation index and recurrence or metastasis after interventional therapy in patients with PLC. Methods: From January 2016 to December 2017, 272 patients with PLC admitted to the 941st Hospital of PLA Joint Logistics Support Force were retrospectively collected. All patients received interventional treatment, there were no residual lesions after interventional treatment. The patients were followed up for 5 years to monitor the rates of recurrence or metastasis. The patients were divided into a recurrence or metastasis group (n=112) and a control group (n=160). The differences in clinical features between the 2 groups were compared, and the predictive value of systemic immune inflammation index on recurrence or metastasis after interventional treatment in patients with PLC was analyzed. Results: Compared with the control group (8.12%), the proportion of patients with ≥2 lesions in the recurrence or metastasis group (19.64%) was significantly increased (P=0.005); the proportion of patients with vascular invasion was significantly increased in the recurrence or metastasis group (10.71% vs. 4.38%, P=0.044); albumin decreased significantly in the recurrence or metastasis group (39.69±6.17 vs. 41.69±6.82 g/L, P=0.014); neutrophils (%) were significantly increased in the recurrence or metastasis group (0.70±0.08 vs. 0.64±0.08, P<0.001); lymphocytes (%) were significantly reduced in the recurrence or metastasis group (0.25±0.06 vs. 0.30±0.06, P<0.001); and platelet count was significantly increased in the recurrence or metastasis group (179.22±39.52 vs. 160.81±34.13 109/L, P<0.001). The systemic immune inflammation index was significantly increased in the recurrence or metastasis group (535.23±174.05 vs. 357.84±120.21, P<0.001). Systemic immune inflammation index was valuable in predicting recurrence or metastasis, and the area under the curve was 0.795 (95% CI: 0.742-0.848, P<0.001). Systemic immune inflammation index >405.08 was an independent risk factor of recurrence or metastasis [relative risk (95% CI: 1.878-5.329), P=0.000]. Conclusions: Elevated systemic immune inflammation index is associated with recurrence or metastasis after interventional therapy in patients with PLC.

Cancer-associated fibroblasts induce immunotherapy resistance in hepatocellular carcinoma animal model.

Hepatocellular carcinoma is known to be a common predominant cancer in adults, especially in eastern countries. Immune response and cancer-associated fibroblasts (CAFs) have significant influences on tumor development. However, the interaction between CAFs and immunotherapy is unclear in hepatocellular carcinoma. We measured the number of activated fibroblasts in hepatocellular carcinoma samples and samples taken from normal liver tissues. A total of 20 patients' fresh hepatocellular carcinoma and normal tissues which were surrounding the tumor were obtained from the surgery and used for evaluating alpha-SMA expression. We investigated the effects of CAFs in anti-tumor immunity in hepatocellular carcinoma animal model. The effects of CAFs in inducing anti-PD-1 treatment resistance were also measured in a preclinical animal model. Activated fibroblasts were highly accumulated in hepatocellular carcinoma tissues but not in surrounding normal tissues. CAFs showed a significant tumor-promoting effect in an immunocompetent model. The infiltration and function of some immune cells like myeloid-derived suppressive cells and T-cells were increased by CAFs. CAFs also reduced the number and activation of tumor-infiltrating cytotoxic T-cell in tumor tissue. In the treatment model, tumors with a higher amount of CAFs had been insensitive to therapy with anti-PD-1. CAFs are potent inducers of immunosuppression in hepatocellular carcinoma. Depleting CAFs rescued the antitumor immunity in the hepatocellular model and could be a novel treatment to combine with the existing immunotherapy.

Determination of glomerular filtration rate (GFR) from fractional renal accumulation of iodinated contrast material: a convenient and rapid single-kidney CT-GFR technique.

OBJECTIVES: To develop a convenient and rapid single-kidney CT-GFR technique. METHODS: One hundred and twelve patients referred for multiphasic renal CT and 99mTc-DTPA renal dynamic imaging Gates-GFR measurement were prospectively included and randomly divided into two groups of 56 patients each: the training group and the validation group. On the basis of the nephrographic phase images, the fractional renal accumulation (FRA) was calculated and correlated with the Gates-GFR in the training group. From this correlation a formula was derived for single-kidney CT-GFR calculation, which was validated by a paired t test and linear regression analysis with the single-kidney Gates-GFR in the validation group. RESULTS: In the training group, the FRA (x-axis) correlated well (r = 0.95, p < 0.001) with single-kidney Gates-GFR (y-axis), producing a regression equation of y = 1665x + 1.5 for single-kidney CT-GFR calculation. In the validation group, the difference between the methods of single-kidney GFR measurements was 0.38 ± 5.57 mL/min (p = 0.471); the regression line is identical to the diagonal (intercept = 0 and slope = 1) (p = 0.727 and p = 0.473, respectively), with a standard deviation of residuals of 5.56 mL/min. CONCLUSION: A convenient and rapid single-kidney CT-GFR technique was presented and validated in this investigation. KEY POINTS: • The new CT-GFR method takes about 2.5 min of patient time. • The CT-GFR method demonstrated identical results to the Gates-GFR method. • The CT-GFR method is based on the fractional renal accumulation of iodinated CM. • The CT-GFR method is achieved without additional radiation dose to the patient.

Percutaneous radiofrequency ablation guided by contrast-enhanced ultrasound in treatment of metastatic hepatocellular carcinoma after liver transplantation.

This study evaluated the advantages and applications of contrast-enhanced ultrasound (CEUS)-supported percutaneous radiofrequency ablation (RFA) in the treatment of metastatic hepatocellular carcinoma after liver transplantation, based on clinical details. CEUS-supported percutaneous RFA was adopted to treat 12 patients with hepatic metastatic carcinomas after liver transplantation. The diameters of the metastatic carcinomas varied from 1 cm to 5 cm, and the foci were discovered after 3 months to 12 months. Each focus was diagnosed and localised by CEUS for RFA once or twice. Curative effects were evaluated by CEUS or contrast-enhanced CT after the treatment. The re-examination results at 2 weeks post-treatment showed that the foci of 11 patients were ablated completely, whereas one patient with the largest focus required retreatment by RFA because of a partial residue. No local recurrence was found one month later in the re-examination. CEUS-supported percutaneous RFA in the treatment of hepatic metastatic carcinoma after liver transplantation has the advantages of accurate localisation, good efficacy, easy operation, and minimal invasion without any complications. Therefore, it can be recommended as the preferred therapy for hepatic metastatic carcinoma after liver transplantation.