Novel organoid construction strategy for non-involuting congenital hemangioma for drug validation.

BACKGROUND: Non-involuting congenital hemangiomas (NICHs) are fully formed vascular tumors at birth with distinctive clinical, radiologic, and histopathological profiles. In the literature, there is no effective therapy strategy for patients with NICH except surgery. Currently, no cell line or animal model exists for studying the mechanism of NICH and drug validation. We plan to construct a new strategy by constructing NICH organoids for further study. RESULT: Here, we report a novel NICH organoid system construction and optimization process. Both HE and immunohistological staining exactly matched NICH tissue. We further performed transcriptome analysis to elucidate the characteristics of NICH organoids. Both NICH tissue and NICH organoids manifested similar trends in download sites. NICH organoids display novel features to new cells derived from organoids and show spectacular multiplication capacity. In the preliminary verification, we found that cells splitting from NICH organoids were human endothelial cells. Drug validation demonstrated that trametinib, sirolimus, and propranolol showed no inhibitory effects on NICH organoids. CONCLUSION: Our data show that this new NICH-derived organoid faithfully captured the features of this rare vascular tumor. Our study will boost further research on the mechanism of NICH and drug filtering in the future.

IPACK (Interspace between the Popliteal Artery and the Capsule of the Posterior Knee) Block Combined with SACB (Single Adductor Canal Block) Versus SACB for Analgesia after Total Knee Arthroplasty.

OBJECTIVES: To evaluate the combination of the infiltration between the popliteal artery and the posterior capsule of the knee (iPACK) block and single adductor canal block (SACB) versus SACB for motor-sparing knee analgesia effects after total knee arthroplasty (TKA). METHODS: PubMed, Ovid, Cochrane Library, and other databases were searched from the inception to January 2021. Randomized controlled trials (RCTs) comparing patients receiving iPACK plus SACB with patients receiving SACB after TKA were included. The included studies were assessed by two reviewers according to the Cochrane risk of bias criteria. Meta-analysis was performed with STATA 13.0 software, the risk ratios (RR) and mean differences (MD) were used to compare dichotomous and continuous variables. The primary outcome was ambulation pain and secondary outcomes were rest pain, opioid consumption, function ability, clinical outcomes, and complications. RESULTS: Seven RCTs (304 knees in iPACK + SACB group; 305 knees in SACB group) were included. The follow-up periods ranged from 2 days to 3 months. Pooled data indicated lower pain scores at ambulation (p < 0.0001) for iPACK + SACB. When comparing the pain scores of subgroups analyzed at specific periods, lower scores in subgroups within 12 h (at rest and ambulation) and after 48 h (at ambulation) were observed in the iPACK + SACB group. Analysis demonstrated greater reduction in morphine consumption (p = 0.007) in the iPACK + SACB group. The iPACK + SACB group is also superior to the SACB group regarding function ability, which included range of motion (ROM) (p = 0.001), time up to go (TUG) test (p = 0.030), and ambulation distance (p < 0.0001). No difference was found in clinical outcomes or complications. CONCLUSIONS: With the iPACK added to SACB, pain scores, morphine consumption, functional ability were improved. Additional high-quality studies are required to further address this topic.

Green Plant Pigment, Chlorophyllin, Ameliorates Non-alcoholic Fatty Liver Diseases (NAFLDs) Through Modulating Gut Microbiome in Mice.

Non-alcoholic fatty liver diseases (NAFLDs) along with metabolic syndrome and Type-2 diabetes (T2D) are increasingly prevalent worldwide. Without an effective resolution, simple hepatic steatosis may lead to non-alcoholic steatohepatitis (NASH), characterized by hepatocyte damage, chronic inflammation, necrosis, fatty degeneration, and cirrhosis. The gut microbiome is vital for metabolic homeostasis. Conversely, dysbiosis contributes to metabolic diseases including NAFLD. Specifically, diet composition is critical for the enterotype of gut microbiota. We reasoned that green pigment rich in vegetables may modulate the gut microbiome for metabolic homeostasis. In this study, C57BL/6 mice under a high fat diet (HFD) were treated with sodium copper chlorophyllin (CHL), a water-soluble derivative of chlorophyll, in drinking water. After 28 weeks of HFD feeding, liver steatosis was established accompanied by gut microbiota dysbiosis, intestinal impairment, endotoxemia, systemic inflammation, and insulin resistance. Administration of CHL effectively alleviated systemic and intestinal inflammation and maintained tight junction in the intestinal barrier. CHL rebalanced gut microbiota in the mice under high fat feeding and attenuated hepatic steatosis, insulin resistance, dyslipidemia, and reduced body weight. Fecal flora transplants from the CHL-treated mice ameliorated steatosis as well. Thus, dietary green pigment or the administration of CHL may maintain gut eubiosis and intestinal integrity to attenuate systemic inflammation and relieve NASH.