1.Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers
Zheyu JIN ; Chenlei XIE ; Xinqi FAN ; Shu YANG ; Ruiyi DONG ; Yanyu BAI ; Yarong DING ; Zhongzhi ZHOU ; Li CHEN
Journal of Army Medical University 2025;47(21):2678-2687
Objective To investigate the effects of cinnamic aldehyde(CA)on Bcl-2-associated X protein(Bax)and Bcl-2 homologous antagonist/killer(Bak)in vascular endothelial cells of diabetic ulcer wound tissues,as well as on cell apoptosis.Methods ① Forty-eight healthy SPF-grade male SD rats(5 weeks old,weighing 180~220 g)were randomly assigned to a control group(12 rats)and a diabetes group(36 rats).The diabetic model was established with an intraperitoneal injection of 50 mg/kg STZ-citrate sodium solution and high-fat diet feeding.The diabetes group was further randomly divided into Model group,CA group,and the rb-bFGF group,with 12 animals in each group.Wounds in the Con and Model groups were disinfected and topically treated with normal saline,CA group received topical application of 4 μmol/L CA in PEG 400 gel,and those of the rb-bFGF group were treated with bevacizumab gel.The wound healing rate of each group was calculated at 3,7 and 14 d after intervention.At 14 d after intervention,pathological changes in the wounds were observed with HE staining,and the expression levels of Bax and Bak were detected by Western blotting.② Human umbilical vein endothelial cell line EA.hy926 was treated with 175 mmol/L glucose for 48 h to establish a cell model of high glucose injury.The experimental cells were divided into control group,model group and CA treatment group.Cell scratch test and tube formation test were performed respectively to determine the migration ability and angiogenesis of the cells.The expression levels of Bax and Bak was detected with immunofluorescence assay,and cell apoptosis was detected by TUNEL staining.Results ①The diabetic rats in the Model group exhibited significantly higher blood glucose level(P<0.05),declined wound healing rate at 7 and 14 d after intervention(P<0.05),and enhanced expression levels of Bax and Bak(P<0.05)when compared with the control group.Pathological observation revealed that,at 14 d after intervention,accompanied with inflammatory reactions,dense infiltration of inflammatory cells,fewer new blood vessels,and continuous fluid exudation in the wound were observed in the Model group,but the control group presented complete epithelialization in full-thickness skin.Compared with the conditions in the Model group,both CA and rb-bFGF treatment improved the epithelialization process,with mature granulation tissues,showing good healing condition,promoted wound healing rate(P<0.05),and decreased the expression levels of Bax and Bak(P<0.05).② The results of cell experiments showed that the cells of the model group showed significantly reduced migration ability and tube formation ability(P<0.05),reduced protein levels of Bax and Bak(P<0.05),and lower apoptotic rate(P<0.05)when compared with the cells in the model group.Conclusion CA can inhibit the expression of apoptosis-related proteins Bax and Bak,promote the migration and tube formation of vascular endothelial cells,and inhibit the cell apoptosis under high glucose condition,which may be an important reason for its promoting wound healing in diabetic ulcer rats.
2.Clinical efficacy of pan-immune inflammatory values in predicting prognosis of elderly patients with severe pneumonia
Mei YUAN ; Yarong XIE ; Lijun ZHENG ; Ming WU
International Journal of Laboratory Medicine 2025;46(11):1353-1357
Objective To investigate the clinical efficacy of pan-immune inflammatory value(PIV)in pre-dicting the prognosis of elderly patients with severe pneumonia(SP).Methods A total of 160 elderly patients with SP admitted to this hospital from January to June 2023 were selected as the study group,and 100 elderly patients with common pneumonia in the hospital in the same period were selected as the control group.Ac-cording to the prognosis at discharge,the patients were divided into good prognosis group(128 cases)and poor prognosis group(32 cases).Neutrophil count,platelet count,monocyte count and lymphocyte count were detected by automatic blood cell analyzer,and PIV was finally calculated.Receiver operating characteristic(ROC)curve was used to analyze the prognostic value of PIV in elderly patients with SP.Multivariate Logis-tic regression was used to analyze the prognostic factors in elderly patients with SP.Results The counts of neutrophil,monocyte and PIV in control group were lower than those in study group,and the counts of lym-phocytes,platelet in control group were higher than those in study group,the difference was statistically sig-nificant(P<0.05).Neutrophil,monocyte count and PIV in the good prognosis group were significantly lower than those in the poor prognosis group,and platelet count and lymphocyte count in the good prognosis group were higher than those in the poor prognosis group,with statistical significance(P<0.05).ROC curve analy-sis showed that the area under the curve of PIV in predicting poor prognosis in elderly SP patients was 0.941,which was larger than that of neutrophil,monocyte,platelet count and lymphocyte count(P<0.001).The proportion of mechanical ventilation,C rection protein(CRP)and procalcitonin(PCT)levels in poor progno-sis group were higher than those in good prognosis group(P<0.05).Multivariate Logistic regression analysis showed that mechanical ventilation,CRP,PCT and PIV were independent risk factors for the prognosis of eld-erly SP patients(P<0.05).Conclusion PIV is an independent risk factor for predicting the prognosis of eld-erly patients with SP.PIV is an important prognostic factor for elderly patients with SP.
3.Wenyang-Shengji ointment regulates GRP78/CHOP pathway to inhibit excessive endoplasmic reticulum stress for facilitating diabetic refractory wound repair
Yarong DING ; Shixu ZHENG ; Jun WANG ; Chenlei XIE ; Shuihua FENG ; Zhongzhi ZHOU ; Li CHEN
Chinese Journal of Pathophysiology 2024;40(3):493-501
AIM:To study the regulation of endoplasmic reticulum stress(ERS)using the glucose regulated protein 78(GRP78)/CCAAT/enhancer binding protein homologous protein(CHOP)pathway and explore the related mech-anism of Wenyang-Shengji ointment in facilitating the repair of diabetic refractory wounds.METHODS:To establish a rat model of diabetic refractory wound repair,Sprague-Dawley(SD)rats were fed a high-fat diet and intraperitoneally in-jected with streptozotocin.Subsequently,full-thickness skin defects were induced in the dorsal region of the rats.The ex-periment included 4 groups:normal,model(diabetic refractory wounds),Wenyang-Shengji ointment,and Beifuxin(re-combinant bovine basic fibroblast growth factor gel)groups.The normal and model groups were treated with normal saline after disinfection.In the Wenyang-Shengji ointment and Beifuxin groups,the wounds were topically treated with the re-spective ointments once daily.After 14 d of treatment,wound healing was assessed and quantified using the wound healing rate.Hematoxylin-eosin(HE)staining was employed to examine the micromorphology of the wound tissue.Western blot analysis was performed to measure GRP78,CHOP and caspase-12 levels in the wound tissue.Immunohistochemical analy-sis was used to detect the expression and distribution patterns of GRP78,CHOP and caspase-12 in the wounds.Transmis-sion electron microscopy was used to observe reticulum numbers and swelling.Enzyme-linked immunosorbent assay was used to determine interleukin-1β(IL-1β)level as a pro-inflammatory factor within the wound.RESULTS:Indexes of each group were assessed 14 d after the corresponding intervention.Compared with normal group,the rats in model group exhibited a significant decrease in the wound healing rate(P<0.01),accompanied by increased inflammatory exudation and poor granulation tissue growth.Additionally,there were increases in the expression levels of GRP78,CHOP and cas-pase-12 proteins(P<0.01),as well as a significant elevation in the content of inflammatory factor IL-1β(P<0.01).In contrast,compared with model group,treatment with Wenyang-Shengji ointment resulted in a significant improvement in wound healing rate(P<0.01),reduction in inflammatory exudation,and enhanced granulation tissue growth(P<0.01).Furthermore,there was a notable decrease in the protein expression of GRP78/CHOP/caspase-12 within the wound tissue following treatment with Wenyang-Shengji ointment(P<0.01).The levels of inflammatory factor IL-1β also showed a sig-nificant decrease(P<0.01).CONCLUSION:Wenyang-Shengji promotes the healing of diabetic refractory wounds,which may be associated with the downregulation of the GRP78/CHOP pathway,inhibition of excessive ERS,and reduc-tion in the level of wound cell apoptosis.
4.Mechanism of Wenyang Shengji Ointment in treating diabetic wounds based on network pharmacology and animal experiments
Yarong DING ; Chenlei XIE ; Shuihua FENG ; Zhonghang YUAN ; Wei WANG ; Mulin LIU ; Zhongzhi ZHOU ; Li CHEN
Digital Chinese Medicine 2024;7(1):79-89
Objective To explore the mechanism of Wenyang Shengji Ointment(温阳生肌膏,WYSJO)in the treatment of diabetic wounds from the perspective of network pharmacology,and to veri-fy it by animal experiments. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and related literature were used to screen active compounds in WYSJO and their corresponding targets.GeneCards,Online Mendelian Inheritance in Man(OMIM),DrugBank,PharmGkb,and Therapeutic Target Database(TTD)databases were employed to identify the targets associated with diabetic wounds.Cytoscape 3.9.0 was used to map the ac-tive ingredients in WYSJO,which was the diabetic wound target network.Search Tool for the Retrieval of Interaction Gene/Proteins(STRING)platform was utilized to construct protein-protein interaction(PPI)network.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed to identify signaling pathways be-tween WYSJO and diabetic wounds.AutoDock 1.5.6 was used for molecular docking of core components in WYSJO to their targets.Eighteen rats were randomly divided into control,model,and WYSJO groups(n=6).The model and WYSJO groups were used to prepare the model of refractory wounds in diabetes rats.The wound healing was observed on day 0,5,9,and 14 after treatment,and the wound tissue morphology was observed by hematoxylin-eosin(HE)staining.The expression levels of core genes were detected by quantitative real-time polymerase chain reaction(qPCR). Results A total of 76 active compounds in WYSJO,206 WYSJO drug targets,3 797 diabetic wound targets,and 167 diabetic wound associated WYSJO targets were screened out through network pharmacology.With the use of WYSJO-diabetic wound target network,core targets of seven active compounds encompassing quercetin,daidzein,kaempferol,rhamnetin,rham-nocitrin,strictosamide,and diisobutyl phthalate(DIBP)in WYSJO were found.GO enrich-ment analysis showed that the treatment of diabetes wounds with WYSJO may involve lipopolysaccharide,bacteria-derived molecules,metal ions,foreign stimuli,chemical stress,nutrient level,hypoxia,and oxidative stress in the biological processes.KEGG enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve advanced glycation end products(AGE-RAGE),p53,interleukin(IL)-17,tumor necrosis factor(TNF),hypoxia inducible factor-1(HIF-1),apoptosis,lipid,atherosclerosis,etc.The results of animal experiments showed that WYSJO could significantly accelerate the healing process of diabetic wounds(P<0.05),alleviate inflammatory response,promote the growth of granulation tis-sues,and down-regulate the expression levels of eight core genes[histone crotonyltrans-ferase p300(EP300),protoc gene-oncogene c-Jun(JUN),myelocytomatosis(MYC),hypoxia inducible factor 1A(HIF1A),mitogen-activated protein kinase 14(MAPK14),specificity pro-tein 1(SP1),tumor protein p53(TP53),and estrogen receptor 1(ESR1)]predicted by the net-work pharmacology(P<0.05). Conclusion The mechanism of WYSJO in treating diabetes wounds may be closely related to AGE-RAGE,p53,HIF-1,and other pathways.This study can provide new ideas for the phar-macological research of WYSJO,and provide a basis for its further transformation and appli-cation.
5.Analyze the risk factors of secondary myocardial injury to acute organophosphorus pesticide poisoning and the predictive value of serum Furin and sTWEAK for it
Rui LI ; Wei ZHU ; Jie XU ; Yarong XIE
International Journal of Laboratory Medicine 2024;45(20):2480-2484
Objective To investigate the risk factors of myocardial injury secondary to acute organophos-phorus pesticide poisoning(AOPP)and the predictive efficacy of serum Furin and soluble tumor necrosis fac-tor-like weak inducer of apoptosis(sTWEAK).Methods A total of 146 AOPP patients admitted to this hos-pital from February 2021 to February 2023 were selected as the research objects.Three days after admission,they were divided into non-myocardial injury group(84 cases)and myocardial injury group(62 cases)accord-ing to whether they had secondary toxic heart disease.The clinical data of all patients were collected.Univari-ate and multivariate Logistic regression analysis were used to explore the risk factors of secondary myocardial injury in AOPP patients.The serum Furin and sTWEAK levels of all patients were detected by enzyme-linked immunosorbent assay.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum Furin and sTWEAK for secondary myocardial injury in AOPP patients.Results Myocardial injury occurred in 62 of 146 AOPP patients,with an incidence of 42.47%.Univariate analysis showed that there were no statistically significant differences in gender,time from medication to admission,and pesticide type between the two groups(P>0.05).Compared with the non-myocardial injury group,the myocardial in-jury group had significantly higher levels of tropomin Ⅰ and creatine kinase isoenzyme and a significantly high-er proportion of patients with age ≥60 years,severe poisoning,and acute physiology and chronic health evalu-ation(APACHE)Ⅱ score ≥20(P<0.05).The serum levels of Furin and sTWEAK in the myocardial injury group were higher than those in the non-myocardial injury group(P<0.05).The area under curve(AUC)of serum Furin and sTWEAK in predicting secondary myocardial injury in AOPP patients was 0.813 and 0.744,respectively.The AUC of combined prediction of the two was 0.896,which was higher than that of each index alone.Multivariate Logistic regression analysis showed that severe poisoning degree(OR=2.054,95%CI 1.256-3.360),APACHE Ⅱ score ≥20 points(OR=2.323,95%CI 1.334-4.046),serum Furin≥129.48 ng/L(OR=3.380,95%CI 1.689-6.766),serum sTWEAK≥845.86 ng/L(OR=4.988,95%CI 2.057-12.097)were risk factors for secondary myocardial injury in AOPP patients(P<0.05).Conclusion Seconda-ry myocardial injury in AOPP patients is related to the degree of poisoning and APACHE Ⅱ score,and the ser-um Furin and sTWEAK levels increase in patients with secondary myocardial injury in AOPP,which have im-portant clinical significance in predicting patients with secondary myocardial injury in AOPP.
6.Analysis of novel gene mutations in a family with hereditary coagulation factor XI deficiency
Rui LI ; Yarong XIE ; Wei ZHU ; Xiaoyan LI ; Hao LIU
Chinese Journal of Laboratory Medicine 2024;47(8):952-957
Objective:To explore the molecular mechanism of clinical bleeding in a family with hereditary coagulation factor Ⅺ (FⅪ) deficiency caused by a novel mutation of the coagulation factor Ⅺ (FⅪ) gene.Methods:A male proband with hereditary coagulation factor XI deficiency who was admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University due to "adenoid hypertrophy" on February 23, 2023 and his family members (5 people in 3 generations) were selected as research subjects. The clinical data of the proband and family members were collected; the relevant coagulation indexes of all members were tested; those with abnormal coagulation indexes (prolonged activated partial thromboplastin time (APTT), normal thrombin time (PT) and fibrinogen (Fib)) were selected for APTT correction experiment; those with corrected Rosner index (RI) less than 10% were selected to detect FⅪ activity (FⅪ:C) by one-step method, FⅪ antigen (FⅪ:Ag) by ELISA method, and whole exon sequence by Illumina sequencing method. New mutation sites were rated according to the American College of Medical Genetics and Genomics (ACMG) related variation rating guidelines, and bioinformatics software was used to predict the impact of new mutations on protein structure and function.Results:The APTT of the proband, his father and his daughter were all prolonged and their RI were all less than 10%. Further tests revealed that FⅪ:C and FⅪ:Ag of the three were all decreased. Illumina sequencing revealed a new frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ of the three people, and a missense mutation c.G1253T (p.Gly418Val) in exon 11 of FⅪ of the proband′s father. ACMG rated the new mutation as pathogenic, and c.G1253T was a reported possible pathogenic mutation.Conclusion:The heterozygous frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ may be the main molecular mechanism of the disease in this family.
7.Compound ANBP promotes diabetic wound healing by regulating TCA circulation-related enzymes
Wei WANG ; Qian HOU ; Xinling HUANG ; Jun WANG ; Meilin ZOU ; Yarong DING ; Letian GUO ; Chenlei XIE ; Xinyu HUANG ; Li CHEN ; Zhongzhi ZHOU
Chinese Journal of Pathophysiology 2024;40(7):1283-1291
AIM:To investigate the effects of the compound ANBP on wound healing in diabetic rats and ex-plore its mechanism of action.METHODS:Ninety male SD rats were randomly divided into blank,model,compound ANBP,Beifuxin,and nicotinamide mononucleotide(NMN)groups,with 16 rats in each group.Wound healing in each group was observed and samples were taken on days 3,7 and 14 to analyze the wound healing rate.Local histopathological changes were observed using HE and Masson staining.The expressions of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),citrate synthase(CS),isocitrate dehydrogenase(IDH1)and oxoglutarate dehydrogenase(OGDH)were de-tected through immunofluorescence and Western blot.The number and morphology of mitochondria in the wound tissue were observed using transmission electron microscopy.RESULTS:Histomorphological changes revealed significant im-provement in diabetic wound healing in the blank and compound ANBP groups compared to that of the model group.The wound healing rates of the blank,compound ANBP,Beifuxin,and NMN groups were significantly increased on days 3,7,and 14(P<0.01).Compared to the model group,granulation tissue generation was higher in the other groups,cover-ing the wound defect and producing abundant collagen fibers.At 3,7,and 14 days after intervention,the blank,com-pound ANBP,Beifuxin,and NMN groups showed significantly enhanced fluorescence intensities of TCA cycling-related enzymes PDHA1,CS,IDH1,and OGDH indicating increased expression of these enzymes.The levels of the TCA cy-cling-related enzymes were significantly increased(P<0.01)in the compound ANBP,Beifuxin and NMN groups but were significantly decreased(P<0.01)in the model group.An increase in the number and density of mitochondria and a de-crease in the cavitation rate of mitochondria with improved morphology(P<0.05)was observed in the group treated with compound ANBP.CONCLUSION:Compound ANBP may increase the number of mitochondria,improve mitochondrial morphology and function,upregulate the expression levels of PDHA1,CS,IDH1,and OGDH proteins,and accelerate the regeneration of wound granulation tissue,thus promoting the healing of diabetic wounds in rats.
8.Mechanism of Cinnamaldehyde in Promoting Wound Healing in Diabetes Rats via PINK1/Parkin-mediated Mitochondrial Autophagy
Kaiqi HONG ; Li CHEN ; Zhenhua ZHU ; Yumeng WANG ; Zhonghang YUAN ; Wei WANG ; Yarong DING ; Chenlei XIE ; Zhongzhi ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):134-143
ObjectiveTo establish a rat model of diabetic wound by feeding on a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) and surgical preparation of full-thickness skin defects, observe the effect of cinnamaldehyde on the wound healing of diabetes rats, and explore the therapeutic mechanism of cinnamaldehyde in improving wound healing of diabetes rats based on the PTEN-induced putative kinase (PINK1)/Parkin pathway-mediated mitochondrial autophagy. MethodForty-eight male SD rats were randomly divided into blank group (n=12) and diabetes group (n=36). The diabetes group was further randomly divided into model group, cinnamaldehyde group, and Beifuxin group, with 12 rats in each group. The blank group and the model group received routine disinfection with physiological saline after creating the wounds, while the cinnamaldehyde group received topical application of polyethylene glycol 400 (PEG 400) gel containing 4 μmol·L-1 cinnamaldehyde, and the Beifuxin group received topical application of Beifuxin gel. Dressings were changed once daily. The wound healing rate of each group was observed. On the 7th and 14th days after intervention, the wound tissues of the rats were collected. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the local tissues. Immunohistochemistry (IHC) was used to detect the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and collagen fibers. Immunofluorescence (IF) and Real-time polymerase chain reaction (Real-time PCR) were used to detect the protein, and mRNA expression of PINK1, Parkin, microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ). ResultAfter intraperitoneal injection of STZ, compared with the blank group, the random blood glucose values of rats in the diabetic group increased significantly (P<0.01), all higher than 16.7 mmol·L-1, and persistently hyperglycemic for some time after modeling. Compared with the blank group, the model group showed poor growth and healing of granulation tissue in the wounds, and the wound healing rate decreased (P<0.01). On the 7th day after intervention, the blank group had squamous epithelial coverage on the wounds. Compared with the blank group, the model group only had a small amount of scab at the wound edges, with a large number of infiltrating inflammatory cells in the wounds. The protein expression levels of IL-6 and TNF-α in the tissues increased (P<0.01), and the protein and mRNA levels of PINK1, Parkin, and LC3Ⅱ decreased (P<0.01). On the 14th day after the intervention, the granulation tissue in the wounds of the blank group was mature and well-healed. Compared with the blank group, the model group still had infiltrating inflammatory cells and red blood cell exudation. The protein expression levels of VEGF and collagen fibers in the tissues decreased (P<0.01), and the protein and mRNA expression levels of PINK1, Parkin, and LC3Ⅱ increased (P<0.01). Compared with the model group, the cinnamaldehyde group and the Beifuxin group showed better wound healing, with increased wound healing rates (P<0.01). On the 7th day after intervention, the protein expression levels of IL-6 and TNF-α in the tissues decreased (P<0.01), and the protein and mRNA expression levels of PINK1, Parkin, and LC3Ⅱ increased (P<0.01). On the 14th day after intervention, the protein expression levels of VEGF and collagen fibers in the tissues increased (P<0.01), and the protein and mRNA expression levels of PINK1, Parkin, and LC3Ⅱ decreased (P<0.01). ConclusionCinnamaldehyde can promote the wound healing of diabetes rats by increasing the wound healing rate, reducing the levels of inflammatory factors IL-6 and TNF-α, and increasing the levels of VEGF and collagen fibers. Its mechanism may be related to the regulation of the PINK1/Parkin signaling pathway, activation of mitochondrial autophagy, inhibition of inflammatory responses, and promotion of angiogenesis and collagen synthesis, thereby promoting the wound healing of diabetes rats.
9.Research hotspots of atrial fibrillation and stroke-related nursing based on CiteSpace
Yanrong LI ; Wenting XIE ; Lijun HAN ; Yarong WANG
Chinese Journal of Modern Nursing 2022;28(27):3729-3734
Objective:To explore the research hotspots and trends of nursing related to atrial fibrillation and stroke.Methods:Searched on the Web of Science core collection database, CiteSpace.5.8.R3 software was used to analyze the authors, publishing institutions, reference co-citations, and keyword clustering of the retrieved article.Results:A total of 241 articles were included. The number of published papers was increasing year by year, but the overall number of published papers was relatively small. There were many co-authors and close cooperation between institutions. Stroke, anticoagulant therapy, impact, guideline, disease management and nursing homes had become research hotspots.Conclusions:CiteSpace software can intuitively analyze the nursing research hotspots related to atrial fibrillation and stroke, and can provide a research reference for the nursing of atrial fibrillation and stroke-related brain-heart comorbid diseases in China.

Result Analysis
Print
Save
E-mail