Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice.

Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.

Baricitinib alleviates cardiac fibrosis and inflammation induced by chronic sympathetic activation.

Cardiac fibrosis is characterized by the over-proliferation, over-transdifferentiation and over-deposition of extracellular matrix (ECM) of cardiac fibroblasts (CFs). Cardiac sympathetic activation is one of the leading causes of myocardial fibrosis. Meanwhile, cardiac fibrosis is often together with cardiac inflammation, which accelerates fibrosis by mediating inflammatory cytokines secretion. Recently, the Janus kinase/signal transducer and activator of transcription (JAK/STAT3) signaling pathway has been confirmed by its vital role during the progression of cardiac fibrosis. Thus, JAK/STAT3 signaling pathway is thought to be a potential therapeutic target for cardiac fibrosis. Baricitinib (BR), a novel JAK1/2 inhibitor, has been reported excellent effects of anti-fibrosis in multiple fibrotic diseases. However, little is known about whether and how BR ameliorates cardiac fibrosis caused by chronic sympathetic activation. Isoproterenol (ISO), a ß-Adrenergic receptor (ß-AR) nonselective agonist, was used to modulate chronic sympathetic activation in mice. As expected, our results proved that BR ameliorated ISO-induced cardiac dysfunction. Meanwhile, BR attenuated ISO-induced cardiac fibrosis and cardiac inflammation in mice. Moreover, BR also inhibited ISO-induced cardiac fibroblasts activation and macrophages pro-inflammatory secretion. As for mechanism studies, BR reduced ISO-induced cardiac fibroblasts by JAK2/STAT3 and PI3K/Akt signaling, while reduced ISO-induced macrophages pro-inflammatory secretion by JAK1/STAT3 and NF-κB signaling. In summary, BR alleviates cardiac fibrosis and inflammation caused by chronic sympathetic activation. The underlying mechanism involves BR-mediated suppression of JAK1/2/STAT3, PI3K/Akt and NF-κB signaling.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

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.

Nonlinear Model Predictive Impedance Control of a Fully Actuated Hexarotor for Physical Interaction.

In this paper, the problem of a fully actuated hexarotor performing a physical interaction with the environment through a rigidly attached tool is considered. A nonlinear model predictive impedance control (NMPIC) method is proposed to achieve the goal in which the controller is able to simultaneously handle the constraints and maintain the compliant behavior. The design of NMPIC is the combination of a nonlinear model predictive control and impedance control based on the dynamics of the system. A disturbance observer is exploited to estimate the external wrench and then provide compensation for the model which was employed in the controller. Moreover, a weight adaptive strategy is proposed to perform the online tuning of the weighting matrix of the cost function within the optimal problem of NMPIC to improve the performance and stability. The effectiveness and advantages of the proposed method are validated by several simulations in different scenarios compared with the general impedance controller. The results also indicate that the proposed method opens a novel way for interaction force regulation.

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.

Diagnostic value of ultrasound-based hemodynamic examination of superior mesenteric artery for acute suppurative appendicitis / 医疗卫生装备

Objective To investigate the characteristics of hemodynamic changes in superior mesenteric artery(SMA)of patients with acute suppurative appendicitis(ASA)to facilitate the diagnosis of ASA.Methods Ninety-three ASA patients diagnosed by ultrasound and confirmed by pathology in some hospital from January 2015 to December 2022 were enrolled into an ASA group,and 88 soldiers without abnormalities in the annual physical examination at the hospital in 2021 were divided into a control group,and the two groups were compared in terms of SMA hemodynamic indexes including peak systolic velocity(PSV),end diastolic velocity(EDV),resistance index(RI)and systolic/diastolic ratio(S/D).The statistically significant data of the above indexes were selected to draw the ROC curve and obtain the cut-off values.SPSS 22.0 software was used for statistical analysis.Results The PSV was(212±69)cm/s in the ASA group and(118±26)cm/s in the control group,with statistically significant differences(P＜0.05),and the two groups had the differences in EDV,RI,and S/D not statistically significant(P＞0.05).The ROC curve was plotted based on the PSV data,and a cutoff value of 238 cm/s was obtained with an AUC of 0.714.Conclusion Ultrasound examination of SMA hemodynamic changes in suspected ASA patients facilitates a definitive diagnosis and is of guidance for clinical treatment.[Chinese Medical Equipment Journal,2023,44(10):64-67]

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.

PE-1, Encoding Heme Oxygenase 1, Impacts Heading Date and Chloroplast Development in Rice ( Oryza sativa L.).

The duration of the rice growth phase has always been an important target trait. The identification of mutations in rice that alter these processes and result in a shorter growth phase could have potential benefits for crop production. In this study, we isolated an early aging rice mutant, pe-1, with light green leaves, using γ-mutated indica rice cultivar and subsequent screening methods, which is known as the phytochrome synthesis factor Se5 that controls rice flowering. The pe-1 plant is accompanied by a decreased chlorophyll content, an enhanced photosynthesis, and a decreased pollen fertility. PE-1, a close homologue of HY1, is localized in the chloroplast. Expression pattern analysis indicated that PE-1 was mainly expressed in roots, stems, leaves, leaf sheaths, and young panicles. The knockout of PE-1 using the CRISPR/Cas9 system decreased the chlorophyll content and downregulated the expression of PE-1-related genes. Furthermore, the chloroplasts of pe-1 were filled with many large-sized starch grains, and the number of osmiophilic granules (a chloroplast lipid reservoir) was significantly decreased. Altogether, our findings suggest that PE-1 functions as a master regulator to mediate in chlorophyll biosynthesis and photosynthetic pathways.

An Intuitive End-to-End Human-UAV Interaction System for Field Exploration.

This paper presents an intuitive end-to-end interaction system between a human and a hexacopter Unmanned Aerial Vehicle (UAV) for field exploration in which the UAV can be commanded by natural human poses. Moreover, LEDs installed on the UAV are used to communicate the state and intents of the UAV to the human as feedback throughout the interaction. A real time multi-human pose estimation system is built that can perform with low latency while maintaining competitive performance. The UAV is equipped with a robotic arm, kinematic and dynamic attitude models for which are provided by introducing the center of gravity (COG) of the vehicle. In addition, a super-twisting extended state observer (STESO)-based back-stepping controller (BSC) is constructed to estimate and attenuate complex disturbances in the attitude control system of the UAV, such as wind gusts, model uncertainties, etc. A stability analysis for the entire control system is also presented based on the Lyapunov stability theory. The pose estimation system is integrated with the proposed intelligent control architecture to command the UAV to execute an exploration task stably. Additionally, all the components of this interaction system are described. Several simulations and experiments have been conducted to demonstrate the effectiveness of the whole system and its individual components.

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.

Effect of Dezocine on IL-12 and IL-10 secretion and lymphocyte activation by culturing dendritic cells from human umbilical cord blood.

Dezocine has been generally utilized for pain therapy and auxiliary anesthesia. Although it has some advantages on the prevention of some anesthesia related complications, its effect on immune responses remains unclear. Our study investigated the effects of Dezocine on IL-10 and IL-12 secretion and lymphocytes activation by culturing dendritic cells (DCs), and revealed the underlying mechanism. Mononuclear cells were divided into negative control group (GN), positive control group (GP), experimental group (GD; GD5, D7, D9). DCs morphological structure was performed by microscope and its phenotypes were evaluated by flow cytometry. IL-12 and IL-10 levels were determined by ELISA and lymphocyte proliferation capacity was performed by MTT assay. Results showed that typical morphological characters of DCs were observed in GP and GD. The positive cell percentages of CD83, HLA-DR, CD80, CD86 and CD40 in GD were lower than those in GP, but higher than the GN group (P<0.01). IL-12 level in GD was higher than in GP, however, IL-10 was opposite (P<0.01). The optical density in GD was lower than in GP (P<0.05). There were no dose-dependent relationships correlated with DCs phenotypes, IL-12 and IL-10 secretion and lymphocytes activation (P>0.05). Our conclusion was that Dezocine might play a role in immunity by regulating IL-12 and IL-10 secretion, and affecting lymphocyte activity in process of DCs maturation. Our findings reveal an unexpected immuno-regulatory function of Dezocine in DCs and provide an important insight for investigating the effect of opioid drugs in immunologic responses.

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.

[Relationship between the growth rate of corpus callosum and neuromotor delay in premature infants].

OBJECTIVE: To study the relationship between the growth rate of the corpus callosum and neurological motor development in premature infants. METHODS: Fifty infants whose gestational ages were less than 34 weeks and who were admitted to the neonatal intensive care unit from March 2007 to August 2007 were enrolled. From 0 to 6 weeks of postnatal age, the sagittal midline cranial sonography via anterior fontanel was performed, once weekly. The length and the morphology of the corpus callosum were measured. The 52-neuromotor examinations were performed at 3 months of corrected gestational age. RESULTS: The mean length of the corpus callosum was 39.16 mm at birth. The mean growth rate of the corpus callosum during the first 6 weeks of life was 1.05 mm/week. Fourteen infants showed abnormal neuromotor development and 36 had normal-neuromotor function at 3 months of corrected gestational age. A decreased growth rate of the corpus callosum was observed in the abnormal nervimotion group between 2 and 3 weeks (0.68 mm/week vs 1.17 mm/week) and between 4 and 5 weeks (0.86 mm/week vs 1.12 mm/week) after birth compared with that in normal nervimotion group (p<0.05). The total growth rate of the corpus callosum from 2 to 6 weeks after birth in the abnormal nervimotion group was also lower than that in the normal nervimotion group (0.91 mm/week vs 1.15 mm/week; p<0.01). CONCLUSIONS: A neuromotor delay at 3 months of corrected gestational age may be associated with the decreased growth rate of the corpus callosum between 2 and 6 weeks of life in premature infants.

Relationship between the growth rate of corpus callosum and neuromotor delay in premature infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the relationship between the growth rate of the corpus callosum and neurological motor development in premature infants.</p><p><b>METHODS</b>Fifty infants whose gestational ages were less than 34 weeks and who were admitted to the neonatal intensive care unit from March 2007 to August 2007 were enrolled. From 0 to 6 weeks of postnatal age, the sagittal midline cranial sonography via anterior fontanel was performed, once weekly. The length and the morphology of the corpus callosum were measured. The 52-neuromotor examinations were performed at 3 months of corrected gestational age.</p><p><b>RESULTS</b>The mean length of the corpus callosum was 39.16 mm at birth. The mean growth rate of the corpus callosum during the first 6 weeks of life was 1.05 mm/week. Fourteen infants showed abnormal neuromotor development and 36 had normal-neuromotor function at 3 months of corrected gestational age. A decreased growth rate of the corpus callosum was observed in the abnormal nervimotion group between 2 and 3 weeks (0.68 mm/week vs 1.17 mm/week) and between 4 and 5 weeks (0.86 mm/week vs 1.12 mm/week) after birth compared with that in normal nervimotion group (p<0.05). The total growth rate of the corpus callosum from 2 to 6 weeks after birth in the abnormal nervimotion group was also lower than that in the normal nervimotion group (0.91 mm/week vs 1.15 mm/week; p<0.01).</p><p><b>CONCLUSIONS</b>A neuromotor delay at 3 months of corrected gestational age may be associated with the decreased growth rate of the corpus callosum between 2 and 6 weeks of life in premature infants.</p>