epsis is a systemic inflammatory response syndrome triggered by infection， and its high mortality rate is closely associated with immune imbalance， particularly the imbalance in the differentiation of helper T cell （Th） cell subsets [Th1， Th2， Th17， regulatory T cell （Treg） ] . In recent years， traditional Chinese medicine （TCM）， with its characteristics of multi-component and multi-target actions， has demonstrated unique advantages in regulating Th cell differentiation and function， as well as correcting immune imbalances in sepsis， offering new perspectives for immunotherapy of sepsis. This review summarizes relevant studies on the regulation of Th cell differentiation for sepsis treatment by TCM monomers and active ingredients （such as Astragalus membranaceus ， Scutellaria baicalensis ， Coptis chinensis ， Rheum palmatum ， Ganoderma lucidum ， Ginkgo biloba ， and Cistanche deserticola ）， the alcohol extract of Dai Baijie， and TCM formulas and preparations categorized as blood-activating and stasis-removing， purgative and laxative， warming and tonifying yang， and tonifying qi and nourishing yin. The results indicate that these TCM monomers， active ingredients， extracts， formulas， and preparations can regulate the Th1/Th2 and Th17/Treg balance， target the differentiation balance of Th cell subsets， alleviate inflammatory responses， or improve immune suppression， thereby exerting therapeutic effects on sepsis.

Sepsis is a systemic inflammatory response syndrome triggered by infection. It progresses rapidly and tends to develop into multiple organ dysfunction. Tanshinone ⅡA， one of the core active ingredients of Salvia miltiorrhiza， exerts remarkable targeted protective effects against sepsis-induced multiple organ dysfunction. This paper reviews the mechanisms by which tanshinone ⅡA alleviates sepsis-induced multiple organ dysfunction. Tanshinone ⅡA can relieve sepsis-induced lung injury by inhibiting the activity of Toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor- κB， phosphatidylinositol 3-kinase/protein kinase B signaling pathways and maintaining mitochondrial homeostasis. It ameliorates sepsis- induced myocardial injury via suppressing the activation of NOD-like receptor family pyrin domain-containing 3/caspase-1 signaling pathway， downregulating the expression of inflammatory factors and regulating autophagy. It mitigates sepsis-induced renal injury by regulating oxidative stress imbalance and reducing the expression of apoptosis-related proteins. It alleviates sepsis-caused liver injury through inhibiting the release of inflammatory factors and hepatocyte apoptosis. It improves sepsis-induced intestinal barrier dysfunction by upregulating the expression of tight junction proteins and restraining inflammatory responses. Furthermore， it relieves sepsis-associated encephalopathy by activating peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A signaling pathway. Tanshinone ⅡA is expected to be a vital candidate drug for comprehensive prevention and treatment of sepsis. However， interdisciplinary research is required to break through current bottlenecks and realize the transformation from basic experiments to clinical application.

OBJECTIVE To explore the effect of Astragali Radix-Curcuma Zedoaria-Paridis Rhizoma(Qi-Zhu-Zao)combina-tion on inhibiting the growth and metastasis of colon cancer based on the PINK1/Parkin/EMT signaling pathway.METHODS Thirty male BALB/c mice were randomly assigned to five groups:sham operation group,model group,positive control group,high-dose Qi-Zhu-Zao group(5.85 g·kg-1),and low-dose Qi-Zhu-Zao group(2.925 g·kg-1),with six mice in each group.An orthotopic colon cancer model was established in the mice using CT26.WT cells.After 15 days of treatment,tumor and liver tissues were collected from each group.Hematoxylin and eosin(HE)staining was performed to assess tumor metastasis,and transmission electron microscopy was used to observe mitochondrial autophagy in tumor tissues.The expression of mitochondrial autophagy-related proteins PINK1,Parkin,p62,and LC3-Ⅱ/LC3-Ⅰ was analyzed using Western blot and immunohistochemistry(IHC).Additionally,the expression levels of epithelial-mesenchymal transition(EMT)-related proteins and mRNA,including E-cadherin,N-cadherin,Vimentin,and Snail,were detected using Western blot,qPCR,and IHC staining.RESULTS Compared to the model group,mice in the treatment groups exhibited significantly reduced tumor volumes and fewer metastatic foci.Additionally,liver tissues showed pathological changes,and the overall growth condition of the mice was markedly improved;the tumor tissues in the treatment groups displayed selective mitochon-drial autophagy,accompanied by the formation of autophagosomes.The treatment influenced the PINK1/Parkin pathway-mediated mi-tochondrial autophagy biological process,with PINK1,Parkin,p62,and LC3-Ⅱ/LC3-Ⅰ levels being significantly upregulated(P<0.05,P<0.01),the high-dose group exhibited a more significant impact than the low-dose group(P<0.05,P<0.01).Furthermore,the treatment groups also showed significant reductions in the protein and mRNA levels of N-cadherin,Vimentin,and Snail(P<0.05,P<0.01),along with significant increases in the protein and mRNA levels of E-cadherin(P<0.05,P<0.01),these effects were more pronounced in the high-dose group compared to the low-dose group(P<0.05,P<0.01).CONCLUSION The herbal combination of Qi-Zhu-Zao inhibits tumor growth and metastasis to a certain extent in a mouse model of orthotopic transplantation of colon cancer.The underlying mechanism may involve the restoration of mitochondrial function through the PINK1/Parkin signaling pathway and the inhibition of the epithelial-mesenchymal transition(EMT)process,thereby achieving a therapeutic effect on colon cancer.

Objective To compare and find an optimal model for predicting the risk of DKD occurrence in patients with type 2 diabetes mellitus(T2DM).Methods A total of 2005 patients with T2DM were enrolled in this study from The Second Hospital of Shijiazhuang City during December 2017 to December 2022.All the subjects were divided into a training set(n=1403)and a validation set(n=602)according to the ratio of 3∶1 by simple random sampling.With the occurrence of DKD as the outcome variablein the training set,important feature variables were screened by LASSO regression.Six different machine learning models were established according to the feature variables,thenthe optimal model was determined by comparison,and anonlinerisk predictor for DKD occurrence was constructed in patients with T2DM.Results Taking the occurrence of DKD as the outcome variable in the training set,the results of LASSO regression analysis showed that the optimal value of the model was 10-fold cross validation lambda.1se=0.01662473,and 15 characteristic variables with nonzero coefficient were screened out to be related to the occurrence of DKD.The data included sex,age,family history of DM,DM duration,LDL-C,HbA1c,WBC,PDW,Scr,urine α1-microglobulin,urine β2-microglobulin,urine microalbumin,hypertension,hypokalemia,and DR.In the training set and validation set,the prediction performance of XGBoost model was better than that of other models(AUC=0.872,0.893,95%CI 0.853～0.891,0.865～0.921),the sensitivity was 0.779,0.863,and the specificity was 0.721,0.758,respectively.The F1 scores were 0.774 and 0.787.DCA analysis showed that the XGBoost model had a greater net benefit and threshold probability.According to the XGBoost model,the online predictor of DKD risk in T2DM patients was laid out,and two patients were selected for application,the results showed that the predictive value of the model was 0.185 in non-DKD patients,and the predictive value was 0.510 in DKD patients.Conclusions The XGBoost model is the best model for predicting the occurrence of DKD in T2DM patients,and an online predictor was successfully built.

Objective To perform an economic evaluation of ilaprazole in the treatment of patients with peptic ulcer bleeding and low-risk stigmata,and to provide a reference for drug selection.Methods From a societal perspective,we used decision analysis to evaluate the cost and effectiveness of ilaprazole and omeprazole in treating peptic ulcer bleeding patients dur-ing hospital stays.The probabilities of model nodes were taken from phase Ⅲ clinical trial research results,while cost data came from national medical insurance prices,published literature,and hospital databases.Sensitivity analysis and scenario analysis were performed to test the stability of the results.Results A cost minimization analysis was performed.Under the basic setting,the cost of the ilaprazole group was 4 038.99 yuan,and that of the omeprazole group was 3 837.61 yuan,which means that the cost of the ilaprazole group was 201.38 yuan higher.Sensitivity analysis showed that the results were stable.Scenario analysis showed that ilaprazole was more cost-effective than the innovator drug of omeprazole.Conclusion Ilaprazole was less economical than ome-prazole in the treatment of peptic ulcer bleeding patients with low-risk stigmata.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

BACKGROUND:Currently,the mandibular joint prosthesis manufactured at home and abroad needs to rely on screws to fix the condylar part of the prosthesis during the replacement process,and the retention hole is reserved to facilitate the operation during the operation.However,due to the lack of personalized jaw design,the reattachment plate may not fit the jaw,resulting in screw loosening and dislocation.Therefore,personalized condylar prosthesis replacement is of great value in the repair of the temporomandibular joint.OBJECTIVE:To design a personalized condylar prosthesis with an internal GYROID for mandibular condylar repair and reconstruction.METHODS:The GYROID structure was selected in the Rhinoceros 7 software with the single cell size of 6 mm and the wall thickness of 0.2,0.3,0.4,0.5,0.6,0.7,0.8 mm.The mechanical properties of the GYROID structure were analyzed by finite element method.3D printing of GYROID structural test specimens with different wall thickness(0.2,0.3,0.4,0.5,0.6,0.7,and 0.8 mm)was performed to test the mechanical properties of the specimens through room temperature compression experiments.A wall thickness value conforming to the range of mandibular mechanical properties was selected through finite element analysis and room temperature compression test results.An adult male mandibular CT data were used for inverse modeling to design a condylar prosthesis with an internal GYROID.Finite element analysis was used to simulate the movement of the apical staggered position and the opposite-blade jaw position after condylar prosthesis replacement.RESULTS AND CONCLUSION:(1)The results of finite element analysis and room temperature compression experiment showed that the elastic modulus of the GYROID structure increased with the increase of wall thickness.The elastic modulus of the GYROID structure with wall thickness of 0.5-0.7 mm was within the range of the elastic modulus of the mandible(1.5-4.0 GPa).Therefore,the 6 mm monocellular GYROID structural model with a wall thickness of 0.6 mm was selected for the design of the condylar prosthesis.(2)The results of finite element analysis showed that the stress distribution of mandibular model was symmetrical.The stress distribution of the two types of occlusion was roughly the same,and the stress peak was not significantly different.The stress concentrated in the neck of the condylar prosthesis,and the stress on the replacement side was slightly larger than that on the healthy side.The maximum equivalent stress of the whole internal fixation model was 269.34 MPa,and the maximum equivalent stress of the screw was 20.14 MPa.The equivalent stress and equivalent strain values of the prosthesis were greater than that of the opposite edge jaw position when the tooth tip was interlaced.The equivalent stress and equivalent strain values of the screw were smaller than that of the opposite edge jaw position when the tooth tip was interlaced.(3)The results showed that the design and retention of the personalized GYROID condylar prosthesis were good,which was consistent with the mechanical conduction of the mandible.

BACKGROUND:Condylar prosthesis replacement,as one of the surgical methods for the treatment of temporomandibular joint diseases,not only needs to restore the morphology and function,but also needs to ensure long-term stable application.OBJECTIVE:To design finite element analysis of a customized Gyroid condylar prosthesis.METHODS:Gyroid structure specimens with different wall thicknesses(250,350,450,550,650,and 750 μm)were designed by software.Finite element simulation compression experiments were carried out to test the elastic modulus of the specimens.The Gyroid structure wall thickness range that matches the elastic modulus of mandibular cancellous bone and whose pore size meets the osteogenesis conditions was screened out.This range was subdivided and Gyroid structure specimens were made using 3D printing technology.Mechanical compression experiments were carried out on a universal testing machine.The Gyroid structure wall thickness that meets the mechanical properties of mandibular bone,has an easier osteogenesis and a smaller strength was screened out by elastic modulus and compressive strength,and subsequent experiments were carried out.A three-dimensional model of a customized Gyroid condylar prosthesis was designed,and the finite element analysis of the blade jaw position and cusp interdigitation position of the model under natural occlusion was simulated.RESULTS AND CONCLUSION:(1)Finite element analysis results showed that with the increase of wall thickness,the elastic modulus of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 350,450,550,650,and 750 μm matched the elastic modulus of mandibular cancellous bone.Since the subsequent experiments needed to be subdivided into groups and the pore size of the 550,650,and 750 μm wall thickness group(pore size 800-1 000 μm)was within the osteogenesis range.Gyroid structure specimens with wall thickness of 550,600,650,700,and 750μm were selected for mechanical compression experiments on a universal testing machine.(2)The results of mechanical compression experiments showed that with the increase of wall thickness,the elastic modulus and compressive strength of Gyroid structure specimens increased.The elastic modulus of Gyroid structure specimens with wall thickness of 550,600,and 650 μm was within the elastic modulus of the mandibular cancellous bone.Finally,the wall thickness of 650 μm and the pore size of 900 μm were selected to construct the three-dimensional model of the mandibular customized Gyroid condylar prosthesis.(3)The results of finite element analysis of three-dimensional model of the mandibular customized Gyroid condylar prosthesis showed that the stress of the articular disc in the edge-to-edge occlusion was mainly concentrated on the lower surface of the anterior middle band,and the stress of the articular disc in the interposition of tooth tips was mainly concentrated on the lateral surface of the lower surface.The maximum displacement and the maximum equivalent stress of the left and right articular discs in the edge-to-edge occlusion and the interposition of tooth tips were similar.The maximum displacement was 0.031,0.030,0.028,and 0.018 mm,and the maximum equivalent stress was 2.87,2.30,2.73,and 1.71 MPa,respectively.(4)The results showed that the Gyroid structure with a wall thickness of 650 μm was consistent with the mechanical properties of the mandible,which reduced the strength of the titanium alloy and reduced the damage of the articular disc caused by the customized Gyroid condylar prosthesis.

Objective To perform an economic evaluation of ilaprazole in the treatment of patients with peptic ulcer bleeding and low-risk stigmata,and to provide a reference for drug selection.Methods From a societal perspective,we used decision analysis to evaluate the cost and effectiveness of ilaprazole and omeprazole in treating peptic ulcer bleeding patients dur-ing hospital stays.The probabilities of model nodes were taken from phase Ⅲ clinical trial research results,while cost data came from national medical insurance prices,published literature,and hospital databases.Sensitivity analysis and scenario analysis were performed to test the stability of the results.Results A cost minimization analysis was performed.Under the basic setting,the cost of the ilaprazole group was 4 038.99 yuan,and that of the omeprazole group was 3 837.61 yuan,which means that the cost of the ilaprazole group was 201.38 yuan higher.Sensitivity analysis showed that the results were stable.Scenario analysis showed that ilaprazole was more cost-effective than the innovator drug of omeprazole.Conclusion Ilaprazole was less economical than ome-prazole in the treatment of peptic ulcer bleeding patients with low-risk stigmata.

The most common site of bone metastasis in advanced bladder cancer is spine，and jaw metastasis is rare. This article reports a 77-year-old male patient who had a solitary metastatic lesion in the left jaw 1 year after radical cystectomy for bladder cancer. The pathological features of the metastasis were consistent with bladder urothelial carcinoma metastasis. The patient received a GC regimen combined with toripalimab immunotherapy for 4 cycles，followed by maintenance of immunotherapy and anti-bone metastasis protection therapy. No new metastasis was found during the 6-month follow-up.