ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD⁺) metabolic remodeling playing a pivotal role. Dysregulation of NAD⁺ and its associated metabolic pathways sustains increased intracellular NAD⁺ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD⁺ metabolic remodeling in GBM, elucidates the mechanisms by which NAD⁺ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD⁺-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

AIM:To investigate the effects of sodium selenite(SS)on viability,migration and angiogenesis of human non-small-cell lung cancer(NSCLC)H520 and A549 cells.METHODS:The H520 cells,A549 cells,and hu-man umbilical vein endothelial cells(HUVEC)were divided into control group(0 μmol/L SS),low dose group(5 μmol/L SS),middle dose group(10 μmol/L SS),and high dose group(20 μmol/L SS).Cell viability was assessed using the CCK-8 assay,and the half-maximal inhibitory concentration(IC50)was calculated.Cell migration and invasion abilities were determined through wound healing and Transwell assays.The regulatory effects of SS on angiogenesis,vasculogenic mimicry and"mosaic"vascular formation between HUVEC and NSCLC cells were detected using vessel forming assays.The expression of vascular endothelial growth factor(VEGF)in the supernatant of lung cancer cells in each group was de-tected using chemiluminescence.RT-qPCR was used to assess the mRNA expression of VEGF,vascular endothelial growth factor receptor 2(VEGFR2)and angiotensin II(Ang II).Western blot was used to examine the protein levels of VEGF,p-PI3K,and p-Akt in H520 and A549 cells.RESULTS:The IC50 values of SS to HUVEC,A549 cells and H520 cells for 48 h were 6.762,9.003 and 7.356 μmol/L,respectively.Compared with control group,the wound healing rate was significantly decreased in each group treated with SS for 48 h(P<0.01).In HUVEC,the number of migrating cells in middle dose and high dose groups decreased(P<0.01),whereas in lung cancer cells,the number of migrating cells in each group decreased after SS treatment(P<0.01).The mRNA expression levels of VEGF,VEGFR2 and Ang II were lower in high-dose SS group than those in control group(P<0.05 or P<0.01).In H520 cells,compared with control group,the protein levels of VEGF,p-PI3K and p-Akt in SS treatment groups were significantly decreased(P<0.05 or P<0.01).CONCLUSION:Sodium selenite inhibits the viability and migration of HUVEC,H520 cells and A549 cells,and inhibits the formation of vasculogenic mimicry and mosaic vessels in NSCLC cells.This mechanism may be related to the inhibition of PI3K-Akt signaling pathway activation and regulation of VEGF.

Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Objective:To explore the clinical and genetic characteristics of three children with Leguis syndrome.Methods:Three children suspected as Legius syndrome at the Henan Children′s Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c. 751C>T (p.Arg251Ter194) in child 1, c. 229A>T (p.Lys77Ter368) in child 2, and c. 1044_1046delinsC (p.R349fs *11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. Conclusion:All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

Objective:To summarize the best evidence for the use of ankle pump exercises in preventing perioperative lower limb deep vein thrombosis (DVT) in patients undergoing joint replacement surgery and to evaluate its clinical application.Methods:This study utilized an evidence-based continuous quality improvement model. A systematic search was conducted for relevant clinical practice guidelines, expert consensus, systematic reviews, and randomized controlled trials (RCTs) from both domestic and international sources. The best evidence was evaluated and summarized, and audit indicators were developed for baseline assessments. Facilitating and hindering factors were analyzed based on the baseline results. From December 2022 to April 2023, the evidence was applied in the Department of Orthopedics at Henan Provincial People's Hospital. The pre-evidence group for baseline assessments included 36 joint replacement patients and 18 nurses from the orthopedic unit between December 2022 and January 2023, while the post-evidence group included 36 joint replacement patients and the same 18 nurses between March and April 2023. The knowledge level of nurses, the effectiveness of ankle pump exercises, the execution rate, and patient compliance were compared before and after evidence-based practice.Results:A total of 12 articles were included in the study, comprising one clinical practice guideline, five expert consensus papers, one systematic review, and five RCTs. Ten best practices were summarized in terms of applicable populations, exercise assessment, exercise positions, timing, methods, frequency, and patient education. After implementing evidence-based practice, the knowledge scores of nurses on ankle pump exercises significantly improved from (70.56±9.98) to (82.78±8.26) ( P<0.01). The compliance rates of audit items 2, 3, 4, 5, and 6 among nurses increased from 0, 22.2%, 0, 27.8%, and 11.1% respectively, to 94.4%, 94.4%, 83.3%, 100.0%, and 100.0% respectively ( P<0.01). On the patient side, the compliance rates for audit items 7 and 8 increased from 5.6% and 0 to 86.1% and 94.4%, respectively ( P<0.01) . Conclusions:Implementing evidence-based ankle pump exercises to prevent DVT in joint replacement patients can significantly improve nurses' knowledge of evidence-based practice, standardize the practice of ankle pump exercises, and explore balanced educational strategies that enhance patient compliance, ensuring clinical practices are evidence-based.

Objective To investigate the effect of fear-induced stress during pregnancy on the expression of glucose transporters(GLUT)in the placenta,providing evidence for the theory of fetal damage caused by fear-induced stress during pregnancy.Methods Twenty pregnant Wistar rats were randomly divided into a control group and a model group of 10 rats each.In the model group,a fear-induced stress model was established using the modified bystander electroshock method for 20 days.After the experiment,the number of offspring and the weights of the placenta and fetal rats were measured,and the placental efficiency was calculated.Transmission electron microscopy was used to observe the morphological changes of placental cells.Bioinformatics analysis was performed to screen for differential genes in placentas affected by pregnancy stress-phobia,and gene set enrichment analysis was performed.Protein immunoblotting(Western Blot),Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR),and immunohistochemistry were used to detect the expression levels of GLUT1,GLUT3,GLUT6,and GLUT7 proteins and genes.Results The placental efficiency was significantly reduced in the model group compared with that in the control group.The result of transmission electron microscopy in the model group showed that the placental microvilli were sparse and short and that the mitochondria and endoplasmic reticulum were swollen.Gene set enrichment analysis revealed that placental genes were significantly enriched in cellular glucose homeostasis in the model group compared with those in the control group.The result of Western Blot,Real-time PCR,and immunohistochemistry indicated a decrease in both the protein and gene expression levels of GLUT1,GLUT6,and GLUT7 in the placenta of pregnant rats.Conclusions Prenatal exposure to fear-induced stress may lead to adverse pregnancy outcomes.These adverse outcomes are potentially associated with reduced levels of three key GLUTs in the placenta:GLUT1,GLUT6,and GLUT7.

Klebsiella pneumoniae is one of the common pathogens causing hospital-acquired infection. With the wide use of carbapenem in recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged around the world. Carbapenemase production is the main cause of resistance to carbapenem antibiotics in Klebsiella pneumoniae. More than 70% of Klebsiella pneumoniae strains produce carbapenemase. Ceftazidime/avibactam (CAZ/AVI) can effectively treat CRKP infection, especially those caused by CRKP that can produce Klebsiella pneumoniae carbapenemase (KPC) or oxaclillinase (OXA)-48. However, it has been reported that CAZ/AVI-resistant CRKP strains have emerged. In this paper, the epidemiology, risk factors, resistance mechanism and treatment of CAZ/AVI-resistant CRKP were summarized to provide reference for clinical treatment.