OBJECTIVE To investigate the ameliorative effect of ursolic acid on skin inflammation in rats with allergic contact dermatitis （ACD）， and explore its mechanism of action based on the Notch1/hairy and enhancer of split 1 （Hes1） signaling pathway. METHODS The ACD model was established by skin application of 2， 4-dinitrochlorobenzene. Forty successfully modeled rats were randomly divided into model control group （MC group）， ursolic acid low-dose group （UA-L group， 50 mg/kg）， ursolic acid high-dose group （UA-H group， 100 mg/kg）， and ursolic acid high-dose+Notch1 activator group （UA-H+Jagged1 group， 100 mg/kg ursolic acid+50 ng/kg Jagged1）， with 10 rats in each group. Another 10 rats with only hair shedding were selected as the normal control group. Rats in the administration groups were given the corresponding dose of ursolic acid intragastrically or/and Jagged1 by intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last treatment， the skin inflammation status and dermatitis scores of rats in each group were detected. The levels of interleukin-6 （IL-6）， IL-17 and IL-10 in serum and skin tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the pathological morphology of the skin tissue. Immunohistochemical staining and immunoblotting assay were used to detect the protein expressions of Notch1 and Hes1 in skin tissues. RESULTS Compared with the MC group， both the UA-L group and UA-H group exhibited significantly lower dermatitis scores， along with varying degrees of reduction in histopathological skin damage such as inflammatory cell infiltration. Additionally， the levels of IL-6 and IL-17 in serum and skin tissues were markedly decreased， while the levels of IL-10 were significantly increased in both groups； protein expressions of Notch1 and Hes1 were decreased significantly （P＜0.05）， and the improvements in the aforementioned indicators were more significant in the UA-H group （P＜0.05）. Jagged1 could significantly weaken the improvement effects of UA-H on the above indicators （P＜0.05）. CONCLUSIONS Ursolic acid may attenuate the expression of pro-inflammatory cytokines and enhance the expression of anti-inflammatory factors by blocking Notch1/Hes1 signaling pathway， thereby improving dermatitis symptoms in ACD rats.

Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.

ObjectiveBased on network pharmacology and transcriptomics， the mechanism of Zishen Qinggan prescription （ZSQGF） in improving glucose and lipid metabolism in type 2 diabetes （T2DM） model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM， gene ontology（GO）analysis and Kyoto encyclopedia of genes and genomes（KEGG） analysis were conducted， and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin （STZ）. The rats were randomly divided into the control group， model group， metformin （Met， 72 mg·kg^-1） group， and ZSQGF high-， medium-， and low-dose groups （ZSQGF-H， ZSQGF-M， and ZSQGF-L， with 4.8， 2.4， and 1.2 g·kg^-1 raw drug in the solution）. The living status of rats was monitored and the levels of total cholesterol （TC）， total triglycerides （TG）， high density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin（HE） staining and oil red O staining. The differential genes were analyzed through transcriptomics， GO and KEGG analysis， and the protein-protein interaction（PPI） network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results， the protein pathways were identified. The expression levels of nuclear factor-κB （NF-κB）， matrix metalloproteinase（MMP）-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2（Bcl-2） modifying factor（BMF）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， and fatty acid synthase（FASN） was detected by real-time polymerase chain reaction（Real-time PCR）. The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration， the body weight， blood sugar， serum indicators， and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB， MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF， NOX4， and FASN in the ZSQGF-H group， while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN， reducing lipid synthesis， and regulating the NF-κB signaling pathway.

Objective:This study aimed to analyze the genomic characteristics of Varicella-Zoster Virus (VZV) strains circulating in Jilin province from 2010 to 2023.Methods:Vesicle fluid from 78 sporadic cases with VZV infection were collected in Jilin province from 2010 to 2023, after detecting by Real-time PCR, 26 specimens (CT<25) were detected by PCR. Open reading frame 22(ORF22), ORF38 and ORF62 were amplified and analyzed. Genotyping was confirmed by SNPs ORF22 (37902, 38019, 38055, 38081 and 38177) and ORF38 (69424). Vaccine strains were indentified from wild-type strains according to ORF38 (69349) and ORF62 (106262, 107252, and 108111). Sequences were analyzed by homologous comparison and phylogenetic analysis.Results:The comparison with Dumas sequence revealed that SNPs (37902, 38055, 38081 and 38177) in ORF22 and ORF38 (69424) have mutations similar to the pOka strain, which belong to clade 2. Compared to the Dumas and Baike strains, all 26 samples were wild-type strains. JL2016-4 strain changes from threonine to asparaginyl at position 38059, JL2021-4 strain changes from arginine to proline at position 37933, from aspartic acid to tyrosine at position 37935, and from aspartic acid at base 38031 to tyrosine. JL2023-1 strain changes from arginine to leucine at position 37933.Conclusions:VZV has been prevalent for 14 years in Jilin province. The main epidemic strains belong to the clade 2. We should strengthen the monitoring of VZV outbreaks and raise the coverage rate of VZV vaccination.

Purpose To investigate the diagnostic value of multimodal imaging in cardiac lipoma.Materials and Methods The clinical symptoms,echocardiography,CT and cardiac magnetic resonance images of 14 patients with cardiac lipoma diagnosed in Xijing Hospital of Air Force Military Medical University from July 2016 to November 2022 were retrospectively analyzed.Results Five patients with lipoma had symptoms of chest tightness and shortness of breath.A total of 18 lesions were found in 14 cases with cardiac lipoma.The locations of cardiac lipomas were widely distributed in the heart,of which 9 were located under the inner lining of the ventricular lumen(6 in the left ventricle,3 in the right ventricle),5 in the myocardium(4 in the left ventricle wall,1 in the right ventricle wall),3 in the pericardium,and 1 in the right ventricle.Echocardiography of 12 cases showed strong echoic mass image,and CT of 7 cases showed uniform low-density mass image.All patients cardiac magnetic resonance showed high signal of T1WI,and the tumor signal of lipid-pressure sequence decreased significantly.T2WI showed high signal and low signal ring around the tumor,indicating a chemical shift artifact.In the film sequence of heart,the mass could be seen to wobble gently and change in the shape of spontaneous motion cycle.The first perfusion scan did not show perfusion elevation.No enhancement was observed on the delayed enhanced scan.Native T1 mapping showed that the T1 value of mass was significantly lower than that of normal myocarda[(255.9±48.4)ms vs.(994.2±66.4)ms],and the difference was statistically significant(t=-32.5,P<0.001).Conclusion Multimodal imaging can provide objective evidence for clinical diagnosis of cardiac lipoma.Lipomas with extremely low T1 values were found,which is helpful to assist in the diagnosis of cardiac lipoma,clearer observation of the lesions,accurate localization,and strong ability to detect small lesions.Therefore,when cardiac lipoma is suspected,T1 mapping can be used as a routine examination method for the diagnosis and differential diagnosis of cardiac masses.

Objective:To investigate the effects of anterolateral thigh chimeric perforator flap in repairing complex wounds of foot and ankle.Methods:A retrospective observational study was conducted. From May 2018 to June 2022, 23 patients who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University to repair complex wounds of foot and ankle with anterolateral thigh chimeric perforator flaps, including 15 males and 8 females, aged from 20 to 66 years. The wounds were all accompanied by bone exposure and defects, and were complicated with varying degrees of infection. All patients underwent debridement and continuous vacuum sealing drainage treatment for 1 week in stage Ⅰ, with the skin and soft tissue defect area after debridement being 10 cm×5 cm to 22 cm×7 cm. In stage Ⅱ, the anterolateral thigh chimeric perforator flap was used to cover the defective wound, of which the muscle flap was used to fill the deep invalid cavity of the ankle joint or cover bone and internal fixation exposures, and the skin flap was used to cover the superficial wound, with the area of the skin flap ranging from 11 cm×6 cm to 23 cm×8 cm, and the area of the muscle flap ranging from 4.0 cm×2.5 cm to 8.0 cm×5.0 cm. The survival of the flap was observed after operation. During follow-up, the color, texture, appearance, and complications of the flap were observed, the function of ankle joint and its range of dorsiflexion motion and plantar flexion motion were measured, and the scar hyperplasia and muscular hernia in donor area were observed.Results:Ecchymosis and epidermal necrosis occurred at the tip of the flap in 1 patient on 5 days after operation and healed after dressing change for 1 week; the other flaps of patients survived successfully. After 6 to 40 months of follow-up, the color, texture, and shape of flaps were good, but 1 patient was not satisfied with the shape of the flap because of flap swelling; the ankle joint movement was basically normal, the dorsiflexion motion was 15-30°, and the plantar flexion motion was 20-45°; the scar hyperplasia in the donor area of the flap was not obvious, and no muscular hernia occurred.Conclusions:The anterolateral thigh chimeric perforator flap can effectively fill the deep invalid cavity of ankle joint and cover the superficial wound at the same time, with minimal damage to the donor site. So it is an ideal flap for repairing the complex wounds of foot and ankle.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) in the treatment of Crohn′s disease (CD), and to analyze the predictive factors of ADA efficacy.Methods:From January 2020 to December 2020, 49 CD patients treated with ADA at the Department of Gastroenterology, Tenth People′s Hospital of Tongji University of Shanghai were enrolled. The clinical data before treatment were collected. During 12 weeks of ADA treatment, the patients were followed up every 2 weeks, the laboratory examinations were conducted every 4 weeks, and colonoscopy examination was rechecked at the 12th week. The improvement of the main symptoms of patients was assessed at 2nd, 4th, and 6th week during ADA treatment. At the 12th week after ADA treatment, the clinical response (Crohn′s disease activity index (CDAI) score decreased ≥70 points from baseline), clinical remission (CDAI score < 150 points), endoscopic response (simple endoscopic score for Crohn′s disease (SES-CD) decreased >50% from baseline) and endoscopic remission (SES-CD ≤2 points or Rutgeerts score ≤1 point), closure of anal fistula of CD patients complicated with anal fistula and occurrence of adverse reactions during treatment were recorded. The predictive factors of clinical remission of CD patients after ADA treatment for 12 weeks were analyzed. The Mann-Whitney U test and binary logistic regression analysis were used for statistical analysis. Results:The main symptom improved rates of 49 CD patients received ADA treatment at 2nd, 4th and 6th week were 75.5% (37/49), 95.9% (47/49) and 98.0% (48/49), respectively, and the main symptom improved time was 14.0 d (7.0 d, 17.0 d). After ADA treatment for 12 weeks, the clinical remission rate was 55.1% (27/49), the clinical response rate was 73.5% (36/49), the endoscopic remission rate was 43.3% (13/30), the endoscopic response rate was 55.6% (15/27), the anal fistula closure rate was 7/18, and the overall incidence of adverse reactions was 24.5% (12/49). The baseline of fecal calprotectin (FC) level of patients in the clinical remission group (27 cases) was lower than that of the patients in the active disease group (22 cases) (111.0 μg/g, 26.3 μg/g to 125.6 μg/g vs. 540.5 μg/g, 420.2 μg/g to 866.9 μg/g), and the difference was statistically significant ( Z=-4.44, P<0.001). The results of binary logistic regression analysis showed that baseline FC level was an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks ( OR=1.08, 95%confidence interval 1.02 to 1.14, P=0.013). When the baseline FC cut-off value was 172.39 g/g, the sensitivity and specificity of it in predicting clinical remission in CD patients treated with ADA for 12 weeks were 81.48% and 90.91%, and the area under the receiver operator characteristic curve was 0.87 ( P<0.001). Conclusions:ADA is safe and effective in the treatment of CD. The baseline FC level is an independent predictive factor of clinical remission in CD patients treated with ADA for 12 weeks.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

OBJECTIVE：To study the improvement effects of paeon iflorin（PF）on myocardial injury in type 2 diabetes mellitus（T2DM）model rats and its mechanism. METHODS ：The experiment was set up in the normal group ，model group ， positive control group （metformin 90 mg/kg），PF high-dose ，medium-dose and low-dose groups （90，60，30 mg/kg），with 8 rats in each group. Except for normal group ，other groups were given high-glucose and high-fat diet and intraperitoneal injection of streptozotocin （30 mg/kg） to induce T 2DM model. After modeling ， administration groups were given relevant medicine intragastrically，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. The body weight ，fasting blood glucose and oral glucose tolerance were measured ；serum levels of glycosylated serum protein （GSP），total cholesterol （TC），triacylglycerol（TG），glutathione peroxidase （GSH-Px），superoxide dismutase（SOD），malondialdehyde（MDA），creatine kinase isoenzyme-MB （CK-MB） and troponin Ⅰ （cTn Ⅰ） were determined. The pathomorphological changes of myocardium were observed. The apoptosis index of rat cardiomyocytes was （ detected. The protein expression of B-cell lymphoma 2 （Bcl-2），Bcl-2 related X protein （Bax）and caspase- 3 in rat myocardium were detected by immunohistochemistry and Western blot. RE SULTS：Compared with normal group ，the body weight ，serum levels of GSH-Px and SOD ，protein expression of Bcl- 2 in myocardium were decreased significantly in model group（P＜0.01）；while fasting blood glucose ，area under blood glucose curve ，serum levels of biochemical indexes （GSP，TC， TG，MDA，CK-MB，cTnⅠ），cardiomyocyte apoptosis index ，protein expression of Bax and caspase- 3 in myocardium were increased significantly （P＜0.05 or P＜0.01）. The arrangement of myocardium was relatively irregular ，and some muscle fibers were broken. Compared with model group ，except for body weight ，serum levels of SOD and MDA ，the protein expression of Bax in myocardium in PF low-dose group ， above indexes of PF groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：PF can regulate glycolipid metabolism ，enhance antioxidant ability ，inhibit cardiomyocyte apoptosis and improve myocardial injury in T 2DM model rats ；the mechanism may be associated with increasing the protein expression of Bcl- 2 and down-regulating the protein expression of Bax and caspase- 3 in myocardium.

Objective:To explore the mediating effect of psychological capital between occupational fatigue and occupational burnout in nurses of the Operating Room, so as to provide a reference for alleviating nurses' occupational burnout.Methods:From October to December 2020, convenience sampling was used to select 230 nurses of Operating Room from 5 ClassⅢ hospitals in Changchun City as the research object. The General Information Questionnaire, Occupational Fatigue Scale, Psychological Capital Scale, and Occupational Burnout Scale were used to evaluate nurses in the Operating Room. The influence of psychological capital and occupational fatigue on occupational burnout was analyzed. Taking occupational fatigue as the independent variable, psychological capital as the mediating variable, and occupational burnout as the dependent variable, the structural equation model was used to test the mediating effect of psychological capital.Results:A total of 230 questionnaires were distributed, and 212 questionnaires were effectively returned. Among 212 nurses in the Operating Room, the scores of occupational fatigue, psychological capital and occupational burnout were (18.27±4.16) , (80.16±14.48) and (68.48±12.82) respectively. Occupational fatigue and occupational burnout of nurses in the Operating Room were positively correlated ( r=0.648, P<0.01) , psychological capital was negatively correlated with occupational burnout ( r=-0.589, P<0.01) , and occupational fatigue was negatively correlated with psychological capital ( r=-0.584, P<0.01) . The hierarchical linear regression results showed that occupational fatigue had a positive predictive effect on occupational burnout ( P<0.01) , while psychological capital had a negative predictive effect ( P<0.01) . The mediating effect of psychological capital between occupational fatigue and occupational burnout of nurses in the Operating Room was 0.18, accounting for 34.61% of the total effect. Conclusions:The psychological capital of nurses in the Operating Room plays a part of the intermediary role between occupational fatigue and occupational burnout. Improving the psychological capital of nurses in the Operating Room can help reduce their level of occupational burnout.