Cardiac progenitors instruct second heart field fate through Wnts.

The heart develops in a synchronized sequence of proliferation and differentiation of cardiac progenitor cells (CPCs) from two anatomically distinct pools of cells, the first heart field (FHF) and second heart field (SHF). Congenital heart defects arise upon dysregulation of these processes, many of which are restricted to derivatives of the FHF or SHF. Of the conserved set of signaling pathways that regulate development, the Wnt signaling pathway has long been known for its importance in SHF development. The source of such Wnts has remained elusive, though it has been postulated that these Wnts are secreted from ectodermal or endodermal sources. The central question remains unanswered: Where do these Wnts come from? Here, we show that CPCs autoregulate SHF development via Wnt through genetic manipulation of a key Wnt export protein (Wls), scRNA-seq analysis of CPCs, and use of our precardiac organoid system. Through this, we identify dysregulated developmental trajectories of anterior SHF cell fate, leading to a striking single ventricle phenotype in knockout embryos. We then applied our findings to our precardiac organoid model and found that Wnt2 is sufficient to restore SHF cell fate in our model of disrupted endogenous Wnt signaling. In this study, we provide a basis for SHF cell fate decision-proliferation vs. differentiation-autoregulated by CPCs through Wnt.

Changes in clinical outcomes and alignment of the ipsilateral knee and ankle after supramalleolar osteotomy in patients with varus osteoarthritis of the ankle: a short-term follow-up study.

PURPOSE: The purpose of this study was to investigate the changes in clinical outcomes and alignment of the ipsilateral knee and ankle in patients with varus ankle osteoarthritis after supramalleolar osteotomy (SMO). METHODS: We retrospectively reviewed 23 patients (24 ankles) with Takakura II, IIIa and IIIb ankle osteoarthritis treated with SMO between May 2017 and March 2022. The radiologic parameters of ankles contained medial distal tibial angle (TAS), tibiotalar angle (TT), tibial lateral surface (TLS), tibial plafond inclination (TPI) and talar inclination (TI). The radiologic parameters of knees contained medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), the knee joint line orientation relative to ground (G-KJLO) and WBL. Hip-knee-ankle angle (HKA) was also collected. The Takakura system was used for evaluating the ankle osteoarthritis and the Kellgren-Lawrence (KL) system was used for evaluating the knee osteoarthritis. Clinical evaluation of the ankle joints contained American Orthopedic Foot and Ankle Society (AOFAS), range of motion (ROM) and visual analogue scale (VAS). Clinical evaluation of the knee joints contained Japanese Orthopaedic Association Scores (JOA), ROM, VAS. RESULTS: The mean follow-up times were 20.3 ± 7.3 months (range 12-38). According to the radiologic evaluation, the TAS increased from preoperative 84.7° ± 2.0° to 91.2° ± 1.8° at the last follow-up (P < 0.001). The TPI and TI decreased from 4.4° ± 4.2° and 11.0° ± 5.2° to 0.1° ± 4.7° and 4.1° ± 4.8° (P < 0.001 for both). The TT angel improved from 9.5° ± 4.1° to 4.9° ± 3.3° (P < 0.001). No significant differences were found regarding MPTA, JLCA, G-KJLO, knee WBL and HKA (P > 0.05 for all). The Takakura stage improved after SMO (P < 0.001) whilst the KL stage maintains the similar lever (P > 0.05). According to the clinical evaluation, the AOFAS significantly increased from 67.5 ± 10.6 to 88.5 ± 9.3 and the VAS of the ankle decreased from 4.7 ± 1.6 to 1.2 ± 1.1, whilst there were no changes on VAS and even the JOA and knee ROM after SMO (P > 0.05 for all). CONCLUSIONS: SMO can alleviate the symptoms of varus ankle osteoarthritis and delay the time for ankle replacement or arthrodesis by redistributing the abnormal stress of the ankle and restoring the congruence of the tibiotalar joint. In addition, it did not induce the clinical symptoms of knee without compromising lower limb alignment or knee joint line orientation in the short term. LEVEL OF EVIDENCE: Level IV case series.

Mesendodermal cells fail to contribute to heart formation following blastocyst injection.

Blastocyst complementation offers an opportunity for generating transplantable whole organs from donor sources. Pluripotent stem cells (PSCs) have traditionally served as the primary donor cells due to their ability to differentiate into any type of body cell. However, the use of PSCs raises ethical concerns, particularly regarding their uncontrollable differentiation potential to undesired cell lineages such as brain and germline cells. To address this issue, various strategies have been explored, including the use of genetically modified PSCs with restricted lineage potential or lineage-specified progenitor cells as donors. In this study, we tested whether nascent mesendodermal cells (MECs), which appear during early gastrulation, can be used as donor cells. To do this, we induced Bry-GFP+ MECs from mouse embryonic stem cells (ESCs) and introduced them into the blastocyst. While donor ESCs gave rise to various regions of embryos, including the heart, Bry-GFP+ MECs failed to contribute to the host embryos. This finding suggests that MECs, despite being specified from PSCs within a few days, lack the capacity to assimilate into the developing embryo.

Acupuncture alleviates acute peritonitis: A case report.

Many inflammatory and infectious entities can affect the peritoneum acutely, and patients with peritonitis often have painful expressions. Abdominal pain can be aggravated by coughing, breathing, and turning the body. Here we report the case of an 88-year-old patient with acute gastrointestinal perforation. The patient has been experiencing pain in the right lower abdomen, presenting persistent colic. The X-ray of abdomen and abdominal computed tomography showed perforation of digestive tract. In addition to the use of anti-infection and stomach protection agents, we use different analgesic injections, but the effect on reducing the pain was not obvious. After acupuncture treatment, the patient quickly relieved the pain of acute peritonitis in 1 minute. However, to our knowledge, there is few literature showing that acupuncture relieves preoperative opioid-induced hyperalgesia in patients with acute peritonitis. Based on this case, we suggest acupuncture as an option in the management of relieving the pain of acute peritonitis when opioid therapy is ineffective.

A neutrophil extracellular traps-associated lncRNA signature predicts the clinical outcomes in patients with lung adenocarcinoma.

Backgrounds: Neutrophil extracellular traps (NETs) play an important role in the occurrence, metastasis, and immune escape of cancers. We aim to investigate Long non-coding RNAs (lncRNAs) that are correlated to NETs to find some potentially useful biomarkers for lung adenocarcinoma (LUAD), and to explore their correlations with immunotherapy and chemotherapy, as well as the tumor microenvironment. Methods: Based on the The Cancer Genome Atlas (TCGA) database, we identified the prognosis-related lncRNAs which are associated with NETs using cox regression. The patients were then separated into two clusters based on the expression of NETs-associated lncRNAs to perform tumor microenvironment analysis and immune-checkpoint analysis. Least absolute shrinkage and selection operator (LASSO) regression was then performed to establish a prognostic signature. Furthermore, nomogram analysis, tumor mutation burden analysis, immune infiltration analysis, as well as drug sensitivity analysis were performed to test the signature. Results: Using univariate cox regression, we found 10 NETs-associated lncRNAs that are associated with the outcomes of LUAD patients. Also, further analysis which separated the patients into 2 clusters showed that the 10 lncRNAs had significant correlations with the tumor microenvironment. Using LASSO regression, we finally constructed a signature to predict the outcomes of the patients based on 4 NETs-associated lncRNAs. The 4 NETs-associated lncRNAs were namely SIRLNT, AL365181.3, FAM83A-AS1, and AJ003147.2. Using Kaplan-Meier (K-M) analysis, we found that the risk model was strongly associated with the survival outcomes of the patients both in the training group and in the validation group 1 and 2 (p < 0.001, p = 0.026, and p < 0.01). Using receiver operating characteristic (ROC) curve, we tested the sensitivity combined with the specificity of the model and found that the risk model had a satisfactory level of 1-year, 3-year, and 5-year concordance index (C-index) (C = 0.661 in the training group, C = 0.679 in validation group 1, C = 0.692 in validation group 2). We also explored the immune microenvironment and immune checkpoint correlation of the risk model and found some significant results. Conclusion: We constructed a NETs-associated lncRNA signature to predict the outcome of patients with LUAD, which is associated with immunephenoscores and immune checkpoint-gene expression.