AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

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.

Portal vein thrombosis (PVT) is one of the most common complications of liver cirrhosis. The formation of PVT can increase the mortality rate of cirrhotic patients and adversely affect the successful implementation and prognosis of liver transplantation. A hypercoagulable state is a unique mechanism underlying PVT formation in cirrhotic patients. In recent years, the pathogenesis of PVT has gradually been elucidated, with specific mechanisms including the following aspects: systemic and local inflammatory responses lead to vascular endothelial cell dysfunction, thereby promoting the activation of the coagulation system; abnormal activation of the monocyte-macrophage system exacerbates local inflammation, enhancing platelet adhesion and aggregation, and facilitating thrombus formation; an imbalance between the coagulation and fibrinolytic systems results in a sustained hypercoagulable state; and intestinal microbiota dysbiosis induces inflammation and metabolic disturbances, thereby increasing the risk of PVT. This article summarizes the latest research progress on these key mechanisms and their interactions, providing new insights into the molecular and cellular mechanisms of PVT. It also offers directions for the early diagnosis of PVT and the exploration of novel intervention strategies in the future.

Objective A survival outcome prediction model for postoperative pancreatic cancer patients was constructed by applying large-scale data based on the new version of American Joint Committee on Cancer(AJCC)staging using different machine learning algorithms.Methods Based on the Surveillance,Epidemiology,and End Results(SEER)database,synthetic minority over-sampling technique(SMOTE)and synthetic minority over-sampling technique and edited nearest neighbors(SMOTE-ENN)algorithms were used to process unbalanced data,random forest,support vector machine,decision tree,and extreme gradient boosting(XGBoost)algorithms were used to build and compare prognostic models,and Shapley additive explanation(SHAP)was introduced to interpret the models.Results The SMOTE-ENN combined with XGBoost model had the best performance(accuracy rate was 86.2％,precision rate was 95.2％,recall rate was 71.2％,F1 value was 0.762,area under the curve was 0.884,Brier score was 0.108).The calibration curve and decision curve respectively showed that this model had good calibration effect and high clinical application value.In addition,SHAP analysis showed that the most important impact on prognostic outcomes was N stage.Conclusion The XGBoost model has the best performance and can be used as a new high-performance postoperative prognosis prediction model under AJCC staging that conforms to the current clinical staging system,providing theoretical support for predicting postoperative patient survival outcomes and formulating personalized treatment plans.

Objective A survival outcome prediction model for postoperative pancreatic cancer patients was constructed by applying large-scale data based on the new version of American Joint Committee on Cancer(AJCC)staging using different machine learning algorithms.Methods Based on the Surveillance,Epidemiology,and End Results(SEER)database,synthetic minority over-sampling technique(SMOTE)and synthetic minority over-sampling technique and edited nearest neighbors(SMOTE-ENN)algorithms were used to process unbalanced data,random forest,support vector machine,decision tree,and extreme gradient boosting(XGBoost)algorithms were used to build and compare prognostic models,and Shapley additive explanation(SHAP)was introduced to interpret the models.Results The SMOTE-ENN combined with XGBoost model had the best performance(accuracy rate was 86.2％,precision rate was 95.2％,recall rate was 71.2％,F1 value was 0.762,area under the curve was 0.884,Brier score was 0.108).The calibration curve and decision curve respectively showed that this model had good calibration effect and high clinical application value.In addition,SHAP analysis showed that the most important impact on prognostic outcomes was N stage.Conclusion The XGBoost model has the best performance and can be used as a new high-performance postoperative prognosis prediction model under AJCC staging that conforms to the current clinical staging system,providing theoretical support for predicting postoperative patient survival outcomes and formulating personalized treatment plans.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Chronic hepatitis B virus(HBV)infection is a major global public health threat.In areas with moderate to high prevalence of HBV,mother-to-child transmission(MTCT)remains the main source of chronic HBV infection.With the application of combined immunization of hepatitis B vaccine and hepatitis B immunoglobulin in neonates,there has been a significant reduction in the incidence rate of HBV MTCT,but there is still a high risk of HBV MTCT in infants born to mothers with positive HBeAg and high viral loads.Although antiviral therapy for pregnant women with high HBV viral loads in late pregnancy can further reduce the risk of HBV MTCT,it is still difficult to completely block HBV MTCT.A deep understanding of the molecular virological mechanisms of HBV MTCT can provide clear ideas for blocking HBV MTCT,which is of great significance for the prevention and management of HBV MTCT.

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.