OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective The researchers systematically retrieved,evaluated,and summarized the best evidence for the care of nebulized inhalation in adult patients on mechanical ventilation,to provide a basis for standardizing the care of nebulized inhalation in patients on mechanical ventilation.Methods We systematically searched the domestic and foreign databases to collect the evidence on the literature related to nebulization therapy for mechanical ventilation in adults.The time for the retrieval is from the inception of databases until February 2023.There were 3 researchers who evaluated the quality of the literature,and extracted and summarized the evidence based on this subject.Results A total of 19 articles were obtained in database.42 pieces of evidence were summarized,covering pre-assessment of nebulized inhalation,preparation before nebulized inhalation,medication management,selection and standardized use of nebulization devices,respiratory machine mode and parameter settings,equipment management during nebulized inhalation,evaluation of effect,management of adverse reactions,disposal of materials and environment after nebulized inhalation and management of nebulized inhalation for respiratory infectious diseases.Conclusion This study summarized the best evidence for nebulized inhalation nursing in adult patients with mechanical ventilation,so as to provide a reference of standardized nebulized inhalation therapy for such patients,which is conducive to ensuring the safety of patients.

Kidney Transplantation/adverse effects* ; Magnetics ; Anastomosis, Surgical ; Magnetic Phenomena

Background: and Purpose We aimed to determine the clinical features of Miller Fisher syndrome (MFS) in southern China and compare them with those presenting in other countries. Methods: We collected the medical records of patients diagnosed with MFS during 2013–2016.We analyzed the age, sex, onset season, precursor events, clinical symptoms and signs, findings of nerve conduction studies (NCS), cerebrospinal fluid (CSF), therapeutic remedies, nadir time, and length of hospital stay of patients with MFS in southern China. We concurrently compared the differences between urban and rural areas and between patients with incomplete ophthalmoplegia (IO) and complete ophthalmoplegia (CO). Results: The study enrolled 72 patients: 36 from rural areas and 36 from urban areas, and 50 males and 22 females. The mean age at onset was 47.72 years, and 30 (41.7%) and 21 (29.2%) patients developed MFS in spring and winter, respectively. The typical triad of ophthalmoplegia, ataxia, and areflexia was observed in 50 (69.4%) patients. A history of upper respiratory tract infection 1 week before onset was found in 52.8% of the patients, while 5.6% experienced gastrointestinal infections and 48 (73.8%) exhibited albuminocytological dissociation in the CSF study. Only 26 (36.1%) patients presented abnormalities in NCS. Moreover, restricted outward eyeball movement presented in 83.5% of the patients with classic MFS and acute ophthalmoplegia, and bilateral symmetrical ophthalmoplegia presented in 64.2%. With the exception of the higher proportion of NCS abnormalities in urban areas (47.2% vs. 25.0%), urban and rural differences were insignificant regarding sex ratio, age at onset, high-incidence season, precursor events, disease characteristics, and albuminocytological dissociation in the CSF. Furthermore, patients with CO were older than those with IO (64.53±7.69 vs. 43.19±14.40 years [mean±standard deviation], p<0.001). Conclusions The patients with MFS were mostly male and middle-aged, and most presented in winter and (especially) spring. More than half of the patients had clear precursor events, most of which were classic MFS with the typical triad. More than 70% of the patients presented albuminocytological dissociation in the CSF. NCS abnormalities were uncommon in MFS. The age at onset was lower in patients with IO than in patients with CO; bilateral symmetrical extraocular muscle paralysis was the most common symptom, and the external rectus was the most frequently involved muscle.

Objective:To explore the clinical efficacy of ceftazidime/avibactam(CZA)plus aztreonam(ATM)for New Delhi metallo-β-lactamase(NDM)carbapenem-resistant Klebsiella pneumoniae(CRKP)infection after kidney transplantation.Methods:Clinical data are retrospectively reviewed for 11 RT recipients infected with NDM metallo-β-lactamase CRKP admitted into First Affiliated Hospital of Xi 'an Jiaotong University and Affiliated Renji Hospital of Shanghai Jiao Tong University from November 2018 to December 2019.Based upon treatment protocol, they are divided into two groups of ceftazidime/avibactam plus aztreonam(CZA-ATM, 5 cases)and other effective antibiotics(OAA, 6 cases).Age, gender, infection type, drug resistance gene, changes in body temperature and leucocyte count, treatment course and prognosis are summarized.Results:A total of 11 patients with NDM-producing CRKP infection after RT are recruited.There are seven males and four females with an age range of(19~66)(38.9±14.4)years.There are mixed pulmonary and urinary tract infections(3 cases), urinary tract infection(2 cases), pulmonary infection(1 case)and perirenal infection(5 cases).All isolates harbore NDM carbapenemase gene, 5 isolates carry Klebsiella pneumoniae carbapenemase(KPC)gene and 1 isolate contained both imipenemase metallo-β-lactamase(IMP)and verona integron-encoded metallo-β-lactamase(VIM)gene concurrently.Ceftazidime-avibactam plus aztreonam(CZA-ATM)is prescribed in five patients while the remainders receive OAA.No adverse reactions occurred in individuals on CZA-ATM and 2 cases on OAA have adverse reactions with a poor appetite and diarrhea.After 30-day infection, the curative cases of CZA-ATM and OAAs groups reach 4 and 5 respectively.No death occurred in neither groups at Day 30.And 90-day mortality is 0 and 1 respectively.Conclusions:For RT patients infected with NDM-producing CRKP, CZA-ATM combination therapy may be another effective treatment.

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

Humans ; Living Donors ; Tissue and Organ Harvesting ; Nephrectomy ; Printing, Three-Dimensional ; Technology ; Laparoscopy

Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the β-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317-318 del/del), rs11467497 (163-166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.
Male ; Humans ; Asthenozoospermia/metabolism* ; Sperm Motility/genetics* ; Homozygote ; Polymorphism, Single Nucleotide ; Semen ; Sequence Deletion/genetics* ; Spermatozoa/metabolism* ; Nucleotides/metabolism* ; beta-Defensins/metabolism*