Pulmonary lymphangioleiomyomatosis is a rare disease characterized by the abnormal proliferation of pulmonary lymphatic smooth muscle cells. It is common in women and often accompanied by recurrent pneumothorax, chylothorax and progressive dyspnea, imaging characterized by diffuse cystic lesions in both lungs. Pulmonary lymphangioleiomyomatosis progresses aggressively and has a very poor prognosis, with a lack of effective medical treatment options in the advanced stages. Lung transplantation is a safe and effective method for the treatment of advanced pulmonary lymphangioleiomyomatosis, which may significantly improve the survival rate and quality of life of patients. The median survival period after surgery can reach 12 years. This article reviews the pathogenesis, diagnosis, treatment of pulmonary lymphangioleiomyomatosis, and the current status and existing problems of lung transplantation in pulmonary lymphangioleiomyomatosis, aiming to provide a reference for the clinical treatment and subsequent research of pulmonary lymphangioleiomyomatosis.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

ObjectiveTo investigate the effects of licoflavone A on the proliferation and glycolysis of gastric cancer cells in the hypoxic environment. MethodHuman gastric cancer AGS cells were classified into five groups： Normoxia， hypoxia， and low-， medium-， and high-dose （25， 50， 100 μmol·L^-1， respectively） licoflavone A. The cells in other groups except the normoxia group were cultured in the environment with 5% O₂ for 48 h. The cell counting kit-8 （CCK-8） and colony formation assay were employed to examine the proliferation of AGS cells. Cell migration was detected by the scratch assay. The protein and mRNA levels of hypoxia-inducible factor 1-alpha （HIF-1α）， glucose transporter 1 （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and hexokinase Ⅱ （HK2） in AGS cells were measured by Western blotting and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. The corresponding kits were used to determine glucose uptake and HK activity. ResultThe CCK-8 results showed that compared with the hypoxia group， the high- and medium-dose licoflavone A groups showed decreased proliferation rate of AGS cells at the time point of 24 h （P<0.01） and all the licoflavone A groups demonstrated decreased proliferation rate at the time point of 48 h （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased number of clone formation of AGS cells （P<0.01）， which was decreased after the treatment with licoflavone A at high， medium， and low doses （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased migration of AGS cells （P<0.01）， which was attenuated by the high， medium， and low doses of licoflavone A （P<0.01）. Compared with the normoxia group， the hypoxia group showed up-regulated mRNA levels of GLUT1， LDHA， PKM2， and HK2 （P<0.05， P<0.01）. Compared with those in the hypoxia group， the mRNA levels of GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group， GLUT1， LDHA， and HK2 in the medium-dose licoflavone A group， and HK2 in the low-dose licoflavone A group were down-regulated （P<0.05， P<0.01）. The protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the hypoxia group were higher than those in the normoxia group （P<0.05， P<0.01）. Compared with those in the hypoxia group， the protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group and HK2 in the medium- and low-dose licoflavone A groups were down-regulated （P<0.05， P<0.01）. The glucose uptake and HK activity were elevated in the hypoxia group compared with those in the normoxia group （P<0.01）. Compared with the hypoxia group， high-dose licoflavone A decreased the glucose uptake and HK activity， and medium-dose licoflavone A decreased the HK activity （P<0.01）. ConclusionLicoflavone A inhibits the proliferation of AGS cells under hypoxic conditions by regulating glycolysis in gastric cancer.

ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）. MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg^-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg^-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L^-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot. ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）. ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.

Objective:Exploring the dilemmas faced by adolescents with type 1 diabetes mellitus in self-management during the transition to adult healthcare, to inform healthcare professionals in the delivery of transitional care interventions.Methods:Using descriptive qualitative research methods, in-depth interviews were conducted from August to December 2023 to adolescents with type 1 diabetes mellitus (selected by objective sampling) who met the inclusion and exclusion criteria in the Department of Endocrinology of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and the Shenzhen Children′s Hospital, and the data were analysed inductively using directed content analysis.Results:A total of 12 adolescents with type 1 diabetes mellitus were included for interview, 6 males and 6 females, aged 12-18 years. The self-management dilemmas for adolescents with type 1 diabetes in the transition to adult healthcare can be summarised into 4 themes and 10 sub-themes: disease management dilemmas (weak awareness of disease management, insufficient disease-related knowledge and competence, low adherence to disease management, and restriction of daily activities), role adaptation difficulties (lack of perceived transition to the healthcare role, difficulty in transitioning to the family role, and maladaptation to the social role), negative emotions Inadequate social support system (lack of school support, limited accessibility of social organisations, insufficient socio-economic support).Conclusions:Adolescents with type 1 diabetes mellitus face multiple dilemmas in disease self-management during the transition to adult healthcare, and healthcare professionals should pay attention to transition self-management education, improve patients′ awareness of transition self-management and their ability to participate in it, formulate a transition preparation plan, build an emotional support network, and improve the social security system, so as to help juvenile patients with type 1 diabetes master the method of self-management and make a successful transition to adulthood.

Existing studies have shown that Astragalus membranaceus(AM)and its active ingredients astragalus polysaccharides,oninon,and astragalus methyl glycosides can attenuate X-ray radiation-induced injury.However,there are no studies on how isoliquiritigenin(ISL)attenuate the bystander effect of bone marrow mesenchymal stem cells(BMSCs)induced by carbon ion radiation therapy for lung cancer.This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect(RIBE)in BMSCs to elucidate its mecha-nism of action.In this study,we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro,and the models were successfully treated with carbon ions.In further work,we used flow cytometry,immunofluorescence,Western blot,enzyme-linked immunosorbent assay(ELISA),inhibitor,short hairpin RNA(shRNA),Cell Counting Kit-8(CCK-8),and other methods to illustrate the mechanism.In the next experiments,we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage.The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings.Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer.These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.

OBJECTIVE To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method. METHODS To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism. RESULTS Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC. CONCLUSION This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.

Objective To illuminate the benefit finding experience of maintenance hemodialysis patients,and to provide a reference for promoting their mental health.Methods From March to May 2023,the purposive sampling was used to select 13 maintenance hemodialysis patients in a tertiary hospital in Shanghai for semi-structured interviews.The data were organized with the help of Nvivo software,and the Colaizzi's seven-step method was used to analyze the data.Results 3 themes were extracted:①the search of meaning,including approved hemodialysis,the desire to live;②gaining a sense of mastery,including adjusting self-psychology,developing healthy living habits,and learning hemodialysis related behavior management;(3)self-enhancement,including excavating external resources and affirming self-worth.Conclusion Maintenance hemodialysis patients have benefit finding experience in many aspects.Medical staff can guide patients to carry out positive psychological construction by strengthening disease knowledge education,building a psychological mutual assistance platform,forming a multidisciplinary nursing team,excavate and provide effective social support resources,and cultivate patients'self-health management,so as to improve the level and ability of benefit finding of patients,experience positive incentives,promote physical and mental health,and improve the quality of life of hemodialysis patients.