Introduction Liver fibrosis is a common response to liver injury and, in severe cases, leads to cirrhosis. The hepatic stellate cells (HSC) become activated after liver injury and play a significant role in fibrogenesis. The activated HSC is characterized by increased proliferation, overexpression of α-smooth muscle actin (α-SMA), and excessive production of extracellular matrix (ECM) proteins. Oridonin, a naturally occurring diterpenoid, has been shown to induce apoptosis in liver and gastric cancer cells. However, its effects on HSC are unknown. Methods We tested the effects of oridonin on the activated human and rat hepatic stellate cell lines LX-2 and HSC-T6 as well as the human hepatocyte cell line C3A. Transforming growth factor β1 (TGF-β1) was used to stimulate LX-2 cells. Results Oridonin significantly inhibited LX-2 and HSC-T6 proliferation. In contrast, Oridonin had no anti-proliferative effect on C3A cells at our tested range. Oridonin induced apoptosis and S phase arrest in LX-2 cells. These findings were associated with an increase in p53, p21, p16, and cleaved PARP, and with a decrease in Cdk4. Oridonin markedly decreased expression of α-SMA and ECM protein type I collagen and fibronectin, blocked TGF-β1-induced Smad2/3 phosphorylation and type I Collagen expression. Conclusions Oridonin induces apoptosis and cell cycle arrest involving the p53/p21 pathway in HSC, and appears to be non-toxic to hepatocytes. In addition, oridonin suppressed endogenous and TGF-β-induced ECM proteins. Thus, oridonin may act as a novel agent to prevent hepatic fibrosis.

COVID-19, caused by the novel coronavirus strain SARS-CoV-2 that emerged in late 2019, has resulted in a global pandemic. COVID-19 was initially believed to occur less frequently in children with relatively mild disease. However, severe disease and varied presentations have been reported in infected children, one of such being intussusception. There have only been three reported cases of intussusception in the pediatric population infected with COVID-19. In this paper, we will discuss the management and treatment of a novel fourth case of COVID-19-associated intussusception. This case is the first reported in the USA and suggests that COVID-19 may be implicated in the development of intussusception. Pediatricians should consider the possibility of intussusception when a child with COVID-19 presents with abdominal pain.

Background Sepsis remains the largest preventable source of neonatal mortality in the world. Heart rate variability (HRV) analysis and noninvasive cardiac output, have been shown to be useful adjuncts to sepsis detection in many patient groups. Methods With IRB approval, 4 septic and 6 nonseptic ELBW patients were enrolled. Data from septic and healthy patients were collected for 5 hours. ECG waveform and traditional vital signs were collected and the RR intervals were calculated, then heart rate variability analysis was performed in both the time- and frequency-domain. Results HRV measurements in time-domain, HR, and Sp02 were significantly different in septic patients vs. nonseptic controls Conclusion These results indicate that nonconventional vital signs such as HRV are more sensitive than traditionally used vital signs, such as CO and MAP, in the confirmation of sepsis in ELBW neonates. HRV may allow for earlier identification of septic physiology.

Background/Objectives:Phenylketonuria (PKU) is an autosomal recessive disease caused by deficient activity of phenylalanine hydroxylase. A low phenylalanine (Phe) diet is used to treat PKU. The diet is very restrictive, and dietary adherence tends to decrease as patients get older. Methods to improve dietary adherence and blood Phe control are continuously under investigation.Subjects/Methods:A new formula Phe-neutral amino acid (PheLNAA) has been tested in this study with the purpose of improving the compliance and lowering blood phenylalanine. The formula has been tested for nitrogen balance, and it is nutritionally complete. It is fortified with more nutritional additives that can be deficient in the PKU diet, such as B12, Biotin, DHA, Lutein and increased levels of large neutral amino acids to help lower blood Phe. The new formula has been tested on 12 patients with a loading test of 4 weeks.Results:Fifty-eight percent of patients had a significant decline in blood Phe concentration from baseline throughout the study. The PheLNAA was well tolerated with excellent compliance and without illnesses during the study.Conclusions:In conclusion, the new formula is suitable for life-long treatment of PKU, and it offers the PKU clinic a new choice for treatment.

Aim Oridonin, isolated from Rabdosia rubescens, has been proven to possess various anti-neoplastic and anti-inflammatory properties. Previously, we reported the anti-fibrogenic effects of oridonin for liver in vitro. In the present study, we investigated the effects of a newly designed analogue CYD0692 in vitro. Methods Cell viability was measured by Alamar Blue assay. Cell apoptosis was assessed by Cell Death ELISA and Yo-Pro-1 staining. Western Blots were performed for cellular proteins. Flow Cytometry was used to measure cell cycle regulation. Results CYD0692 significantly inhibited LX-2 cells proliferation in a dose- and time-dependent manner with an IC50 value of ~0.7 μM for 48 hours, ~10 –fold greater potency than oridonin. Similar results were observed in HSC-T6 cells. In contrast, on the human hepatocyte cell line C3A, only 12% of the cell growth was inhibited with 5 μM of CYD0692 treatment for 48h, while 30% inhibited at 10 μM. After CYD0692 treatment on LX-2 cells, apoptosis and S-phase cell cycle arrest were induced; cleaved-PARP, p21, and p53 were activated while cyclin-B1 levels declined. In addition, α-smooth muscle actin, type I Collagen, and fibronectin (FN) were markedly down regulated. Transforming growth factor β1 (TGF β1) has been identified as a dominant stimulator for ECM production in HSC. Our results indicated that pre-treatment with CYD0692 blocked TGF β1-induced FN expression, thereby decreasing the downstream factors of TGF β1 signaling, such as Phospho-Smad2/3 and phospho-ERK. Conclusion In comparison with oridonin, its novel derivative CYD0692 has demonstrated to be a more potent and potentially safer anti-fibrogenic agent for the treatment of hepatic fibrosis.