ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment （温阳生肌膏， WSO） in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group （n=6） and modeling group （n=18）. The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection， full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet， and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups， the model group， the WSO group， and the Beifuxin （Recombinant Bovine Basic Fibroblast Growth Factor Gel， BX） group， 6 rats in each group. The WSO group was given the ointment to the wound， the Beifuxin group was givne BX gel， and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0， 3， 7， and 14， and the wound healing rate was calculated on day 3， 7， and 14. On day 14 after treatment， HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF）. Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue， and ELISA was used to detect the methylglyoxal （MGO） content in the wound tissue. ResultsCompared with the normal group， the model group showed poor wound healing on day 3， 7， and 14， with a low wound healing rate （P＜0.01）. HE staining showed scab coverage on the wound， with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced， while the relative protein levels of HIF-1α and the MGO content significantly increased （P＜0.01）， and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group， the WSO group and Beifuxin group showed better wound healing on day 3， 7， and 14， with an increased wound healing rate （P＜0.01）. The wound tissue showed clear and complete epithelial structure， reduced inflammatory cells， mature granulation tissue， and organized collagen arrangement. MGO content was significantly reduced （P＜0.01）. The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group， while only VEGF increased in the Beifuxin group （P＜0.05 or P＜0.01）. Compared with the Beifuxin group， the WSO group had a thicker epidermal layer， prominent collagen formation， significantly increased HIF-1α fluorescence expression， reduced MGO content in the wound tissue， and higher relative protein levels of HIF-1α （P＜0.05）. ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway， which could be one of the mechanisms for promoting wound healing.

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.

Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.

Objective:To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline.Methods:This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2± 10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index.Results:The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration [0(0, 0) mm] ( Z=-1.03, P=0.394; Z=-2.05, P=0.065). Conclusions:Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.

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.

To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis.

To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis.

Objective Clarify the basis of the commonly used Tibetan medicinal material"YeGexing",the chemical structure and pharmacological activity were investigated,then provide a basis for standardizing clinical medication,quality control,and rational use of resources.Methods Using literature research;plant taxonomy identification summary of chemical composition investigation and pharmacological activity identification,combined with resource distribution,clinical use status investigation and analysis.Results Tibetan medicine"Yegexing"involved 7 species in 2 families,4 genera,that is Sambucus Linn.from Caprifoliaceae,Senecio L.,Synotis(C.B.Clarke)C.Jeffrey et Y.L.Chen,Saussurea DC.from Compositae.The earliest used"Yegexinggabao"or"white"should be Senecio dianthus.and Senecio solidagineus.in the literature;"Yegexingnabao"or"black"should be Saussurea epilobioides.and Sambucus adnate.;S.raphanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.).S.chinensis.are the main substitutes used in Yunnan,Gansu,and western Sichuan,and are commonly used in the market.YeGexing mainly contains terpenes,flavonoids,alkaloids,phenolic acids and other chemical components;YeGexing black is mainly used for"healing",white is mainly used for"anti-inflammatory",which corresponds to modern pharmacological research on anti-inflammatory,antioxidant,antibacterial and other activities.Conclution In view of the fact that the origin of"Yegexing"involves a variety of plants from different families and genera,"Yegexing"has become a collective name for these plant medicinal materials.According to the lextual results and the research progress on chemical structure and pharmacological activity,from the perspective of conducive to standardizing clinical medication,ensuring efficacy and quality of medicinal materials,its name and variety should be standardized as:"??????(???????????????????/)Yegexinggabao"(that is,the white one),the source is S.dianthus.(S.erythropappa.),S.solidagineus.(S.solidaginea.),S.raphalanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.);"(???????????????????????/)Yegexingnabao"(that is,the black one),the source is S.epilobioides.and S.adnata.and S.chinensis are independent medicines.We should strengthen the investigation of the resources and use status of substitutes in various places,the comparative research on the medicinal material basis and biological activity of different resource species,and standardize their varieties-names-bases to make rational use of their resources.

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.