Selpercatinib attenuates bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß1 signaling pathway.

IPF is a chronic, progressive, interstitial lung disease with high mortality. Current drugs have limited efficacy in curbing disease progression and improving quality of life. Selpercatinib, a highly selective inhibitor of receptor tyrosine kinase RET (rearranged during transfection), was approved in 2020 for the treatment of a variety of solid tumors with RET mutations. In this study, the action and mechanism of Selpercatinib in pulmonary fibrosis were evaluated in vivo and in vitro. In vivo experiments demonstrated that Selpercatinib significantly ameliorated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro, Selpercatinib inhibited the proliferation, migration, activation and extracellular matrix deposition of fibroblasts by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathway, and suppressed epithelial-mesenchymal transition (EMT) like process of lung epithelial cells via inhibiting TGF-ß1/Smad pathway. The results of in vivo pharmacological tests corroborated the results obtained from the in vitro experiments. Further studies revealed that Selpercatinib inhibited abnormal phenotypes of lung fibroblasts and epithelial cells in part by regulating its target RET. In short, Selpercatinib inhibited the activation of fibroblasts and EMT-like process of lung epithelial cells by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathways, thus alleviating BLM-induced pulmonary fibrosis in mice.

A 3-DOF electromotor-driven external fixator for foot and ankle deformity correction based on X-ray digital measurement.

BACKGROUND: The use of external fixators to treat foot and ankle deformities remains a challenge in orthopedic surgery due to their diversity. We hope to improve the automation and accuracy of the correction process. METHODS: A three-degree-of-freedom (3-DOF) electromotor-driven external fixator for uniplanar foot and ankle deformities was proposed. Computer-assisted correction software was developed to help surgeons use digital technology to measure the required parameters from patients' X-ray radiographs. The correction trajectory and the prescriptions were generated in the software based on the proposed correction strategy. RESULTS: Two clinical cases were simulated to verify the correction ability of the developed external fixator. The results showed that the angular and displacement deformities were well corrected. CONCLUSIONS: The developed external fixator can accurately and automatically correct foot and ankle deformities with the help of computer-assisted correction software, which significantly reduces the burden on surgeons and patients.

Ultrasound-Guided Quadratus Lumborum Block Combined with General Anaesthesia or General Anaesthesia Alone for Laparoscopic Radical Gastrectomy for Gastric Adenocarcinoma: A Monocentric Retrospective Study.

Purpose: To investigate, in patients with gastric carcinoma undergoing laparoscopic radical gastrectomy, the effects of ultrasound-guided quadratus lumborum block (UG-QLB) combined with general anaesthesia (GA) on the postoperative recovery compared with GA alone. Patients and Methods: The retrospective study enrolled 231 patients with gastric carcinoma undergoing laparoscopic radical gastrectomy, including 119 patients who received UG-QLB combined with GA (Group QG), and 112 patients undergoing GA alone (Group GA). The primary endpoint was the postoperative 3-year recurrence-free survival (RFS). The secondary endpoints were the average visual analogue scale (VAS) scores within 48 h after surgery, the first time of postoperative ambulation, the first time of flatus, postoperative hospitalization, perioperative opioid requirement and adverse effects after surgery. Results: UG-QLB combined with GA did not affect the 3-year RFS in patients undergoing laparoscopic radical gastrectomy (HR 0.659, 95% CI 0.342-1.269, P=0.212). However, the VAS ranking analysis implicated that it could significantly alleviate the postoperative pain in laparoscopic radical gastrectomy patients (P<0.01). In addition, it dramatically facilitated the early recovery of postoperative ambulation and flatus, while shortening the duration of postoperative hospitalization (P<0.01). The most important was it could remarkably reduce the opioid consumption (P<0.01), which in the meanwhile, reduced the incidence of postoperative nausea and vomiting (PONV) (P=0.01). Conclusion: Although UG-QLB combined with GA did not improve the 3-year RFS for patients with gastric carcinoma undergoing laparoscopic radical gastrectomy, it could provide satisfactory postoperative pain relief, reduce opioid consumption and adverse effects, which subsequently facilitates postoperative early rehabilitation.

Updates on the pathogenesis of advanced lung cancer-induced cachexia.

Advanced lung cancer is becoming a chronic disease threatening human life and health. Cachexia has been recognized as the most common problem associated with advanced lung cancer. Lung cancer-induced cachexia seriously affects patients' quality of life. The present article summarizes the pathogenesis of advanced lung cancer-induced cachexia from three aspects: anorexia, cytokines, and energy and metabolic abnormalities. In addition, the present article proposes corresponding nursing measures based on cachexia pathogenesis to improve the quality of life and survival rate of cachectic patients with advanced lung cancer by combining continuously advancing treatment regimens and effective nursing. The present article also provides references for healthcare professionals when administering related treatments and nursing care.

Three goose-type lysozymes in the gastropod Oncomelania hupensis: cDNA sequences and lytic activity of recombinant proteins.

Three goose-type (g-type) lysozymes, designated as OHLysG1, OHLysG2 and OHLysG3 were identified from expressed sequence tags (ESTs) of a gastropod Oncomelania hupensis, the intermediate host of Schistosoma japonicum. The full cDNA sequences of OHLysG1, OHLysG2 and OHLysG3 consisted of 735, 909 and 808 nucleotides, with an open reading frame of 198, 214 and 249 codons containing a 21, 7 and 8 amino acid (aa) signal peptide at the N-terminus, respectively. The three g-type lysozymes shared conserved features with other g-type lysozymes, such as the substrate binding sites, the catalytic residues critical for the fundamental structure and function of g-type lysozymes. It seems possible that g-type lysozymes in molluscs shared one conserved cysteine with those in birds and mammals, and six conserved cysteines were observed for mollusc g-type lysozymes, with two unique cysteines present in the g-type lysozymes of O. hupensis. The three lysozyme genes were expressed mainly in hepatopancreas, with relatively low expression level observed in head-foot muscle and intestine. When comparing S. japonicum-infected and uninfected snails, significant increase (P<0.05) was observed for all the three lysozymes in infected snails, with the highest increase detected in hepatopancreas, and lowest in intestine, implying their defensive role in the host-parasite, i.e. snail-trematode system. The three recombinant lysozymes expressed in Escherichia coli strain M15 showed lytic activity against Aeromonas hydrophila, Vibrio fluvialis, Aeromonas sobria and Micrococcus lysodeikticus. In conclusion, the finding of three g-type lysozymes in O. hupensis provides structural and functional evidence of multiple g-type lysozymes in gastropod, which may have evolutional implication in the snail-trematode system.