ObjectiveThis paper aims to study the potential active compound components and action mechanism of Shenqi Dihuangtang in the treatment of diabetic kidney disease （DKD） through network pharmacology and in vivo experimental verification. MethodsUltra-high-performance liquid chromatography-Q-exactive orbitrap mass spectrometry （UPLC-Q-Exactive Orbitrap MS） technology was used to clarify the main active chemical components of Shenqi Dihuangtang， and it was combined with network pharmacology methods such as gene ontology （GO） functional annotations and Kyoto encyclopedia of genes and genome （KEGG） to predict the potential action mechanism of Shenqi Dihuangtang in treating DKD. Subsequently， the DKD model of db/db male mice was established， and the mice were randomly divided into model group， low-dose Shenqi Dihuangtang group （6.10 g·kg^-1）， medium-dose Shenqi Dihuangtang group （12.19 g·kg^-1）， high-dose Shenqi Dihuangtang group （24.38 g·kg^-1）， and daplizin group （1.25 mg·kg^-1）. During the same period， C57BL/6J male mice were selected into normal group and received drug intervention for 8 weeks， respectively. During this period， the body weight and fasting blood glucose （FBG） of the mice were dynamically monitored， and oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed at the end of dosing. The levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， uric acid （UA）， albumin （ALB）， and total protein （TP） were measured by an automatic biochemical analyzer， and 24-hour urine protein was measured by a urine protein quantitative kit. Hematoxylin-eosin （HE）， periodic-acid Schiff （PAS）， and Masson staining were employed to observe the renal histopathology. The expression of nephrotic protein Nephrin was observed by immunohistochemistry. Western blot was used to detect the expression of epithelial-mesenchymal transition （EMT）-related proteins such as TGF-β₁， Smad2/3， α-smooth muscle actin （α-SMA）， neural-cadherin （N-Cadherin）， and snail protein. ResultsUPLC-Q-Exactive Orbitrap MS identified 384 active compounds in the aqueous extract of Shenqi Dihuangtang. According to oral bioavailability≥30% and the five drug-like principles， 44 key active ingredients were screened out， and 169 intersection targets highly correlated with DKD were matched. Among them， there was a significant interaction relationship between tumor necrosis factor（TNF）， interleukin（IL）-6， protein kinase B（Akt）1， Caspase-3， Jun proto-oncogene （JUN）， hypoxia inducible factor-1α（HIF-1α）， B cell lymphoma-2（Bcl-2）， matrix metallopeptidase-9（MMP-9）， IL-1β， and TGF-β₁. GO functional annotations were significantly enriched in cellular components such as membrane rafts， membrane microdomains， and collagen-containing extracellular matrix， molecular functions such as DNA-binding transcription factor binding， R-Smad binding， and Smad protein binding， as well as biological processes such as reactions to lipopolysaccharides（LPS）， reactions to bacteria-derived molecules， and wound healing. The KEGG pathway was significantly enriched in lipids and atherosclerosis， TGF-β signaling pathway， phosphatidylinositol 3 kinase （PI3K）/Akt signaling pathway， etc. In vivo experimental results showed that the high-dose Shenqi Dihuangtang group could significantly reduce FBG levels in db/db mice （P<0.01）， improve OGTT （P<0.01） and ITT （P<0.01） levels， reduce SCr （P<0.01）， BUN （P<0.01）， UA （P<0.01） and 24-hour BUN （P<0.01）， and increase ALB （P<0.01） and TP （P<0.01） levels. Pathological staining confirmed that the high-dose Shenqi Dihuangtang group could significantly reduce the glomerular mesangial matrix area and collagen deposition （P<0.01） and upregulate the positive expression rate of Nephrin （P<0.01）. Western blot results showed that the high-dose Shenqi Dihuangtang group significantly downregulated the expression of TGF-β₁ （P<0.01） and Smad2/3 （P<0.01） signal molecules and inhibited the protein levels of α-SMA （P<0.01）， N-Cadherin （P<0.01）， and Snail （P<0.01）. ConclusionShenqi Dihuangtang can inhibit the TGF-β₁/Smad signaling axis and block the renal EMT process， thereby improving DKD renal fibrosis damage. Further analysis of its key active components and clinical transformation pathways is needed in the future.

ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

In order to establish a competitive chemiluminescent enzyme-linked immunoassay for rapid and quantitative detection of Senecavirus A antibodies,the polystyrene plate was coated with inactivated Senecavirus A antigen,and the monoclonal antibodies against Senecavirus A VP2 and VP3 proteins labeled by horseradish peroxidase(HRP)were used as the competitive enzymic anti-bodies of the antibodies in the serum samples.The standard curve of the calibrator prepared by di-lution of positive serum was drawn to achieve quantitative detection.The successfully established SVA competitive CLEIA reported the result within 45 minutes.The maximum dilution of 1∶2 048 for calibrator serum was still detectable with no cross-reaction with the standard positive serum of other five kinds of virus antigens such as foot-and-mouth disease.The coefficient of variation within batches was less than 10％,and the coefficient of variation between batches was less than 15％,which showed good repeatability and stability.The positive and negative coincidence rates were 95.30％and 97.57％,respectively,and the total coincidence rate was 96.88％,showing high consistency.The SVA competitive CLEIA assay established in this study can be used for the rapid quantitative detection of Senecavirus A antibodies,filling the gap in the domestic rapid quantitative detection of SVA antibodies.

Hepatocellular carcinoma(HCC)is a cancer with extremely high mortality and incidence rates.In recent years,with the development of multidisciplinary approaches,key characteristics of cancer have gradually been revealed.Studies have shown that dysregulated energy metabolism and metabolic reprogramming in tumor cells form the basis for tumor cell growth and are critical factors in shaping the tumor microenvironment,immune evasion,and drug resistance.Non-coding RNAs(ncRNAs),as important regulatory factors,play a crucial role in the metabolic reprogramming of HCC.This article focuses on summarizing the mech-anisms by which ncRNAs regulate metabolic repro-gramming in HCC and explores their applications in clinical diagnosis,treatment,and prognostic assess-ment,aiming to provide new perspectives for effec-tive HCC treatment and the development of novel drug targets.

Objective To carry out emergency medical system modification design for EC135 P3H helicopter without compromising the original airframe structure so as to enhance aeromedical rescue capabilities.Methods Firstly,the original cabin seats were removed and medical floor was installed in the cabin;secondly,the medical chair,medical stretcher trolley and its fixing components,storage boxes and oxygen cylinders were mounted onto the floor;finally,a medical equipment fixing frame was formed based on the original helicopter sill structure so as to accommodate medical devices such as defibrillators,ventilators and injection pumps.The modification design scheme had its effectiveness verified with overall aircraft load balance analysis,mechanical analysis,dynamic impact tests of seats and actual modification and flight tests.Results EC135 P3H helicopter proved to meet all the airworthiness certification requirements after emergency medical system modification.Conclusion The proposed modification scheme enables EC135 P3H helicopter to rapidly transition between standard and medical configurations,enhancing its emergency medical rescue capabilities and providing references for medical modifications of helicopters with similar configurations.

OBJECTIVE To establish a risk prediction model for antibiotic-associated diarrhea(AAD)in intensive care unit(ICU)patients receiving mechanical ventilation so as to provide bases for early identification of high-risk population and formulation of corresponding individualized prevention strategies.METHODS A total of 1016 pa-tients who received mechanical ventilation and were treated with antibiotics in the ICU of The First Medical Center of Chinese PLA General Hospital from Jan.1,2020 to Jun.30,2022 were retrospectively enrolled in the study and were divided into the AAD group with 200 cases and the non-AA group according to the diagnostic criteria for AAD.Multivariate logistic regression analysis was performed for risk factors for AAD in the ICU patients receiv-ing mechanical ventilation,and the nomogram prediction model was established with R software.The performance of the model was evaluated by means of receiver operating characteristic(ROC)curves and calibration curves.RESULTS Among the 1016 patients who underwent mechanical ventilation,200 had AAD,and the incidence rate of AAD was 19.69％.Multivariate logistic regression analysis showed that hemoglobulin[OR=0.990,95％CI(0.983 to 0.997)],C-reactive protein[OR=1.046,95％CI(1.009 to 1.085)],serum phosphorus[OR=0.498,95％CI(0.328 to 0.755)],serum lipase[OR=1.001,95％CI(1.000 to 1.002)],ceftriaxo ne sodium[OR=2.331,95％CI(1.253 to 4.334)],linezolid[OR=2.387,95％CI(1.329 to 4.289)],fluconazole[OR=2.083,95％CI(1.238 to 3.505)]and sedatives[OR=0.307,95％CI(0.160 to 0.590)]were the risk factors for the AAD in the ICU patients receiving mechanical ventilation.The area under ROC curve(AUC)of the predic-tion model established based on the risk factors was 0.705 for the training set,0.751 for the validation set.Hos-mer-Lemeshow test indicated that the predicated probability of the model was consistent with the actual risk for the occurrence(x2=6.057,5.304,P=0.641,0.725).CONCLUSION The nomogram model that is established based on the above influencing factors can quantitatively predict the risk for AAD in the ICU patients undergo-ing mechanical ventilation,and it has certain clinical predictive efficiency.

Objective:To investigate the enhancement effect of deep progressive reconstruction (DPR) algorithm on image quality and standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in obese patients. Methods:The images of a total of 27 obese patients,who underwent 18F-FDG PET/CT in Affiliated Nanjing Hospital of Nanjing Medical University from September 2023 to May 2024,were retrospectively enrolled. The images of all patients were collected by using uMI 780 PET/CT. Ordered subset expectation maximization (OSEM) iterative algorithm and DPR algorithm were adopted to reconstruct PET images,and measure counting rate of scattering coincidence of PET/CT images,counting rate of true coincidence,noise equivalent counting rate (NECR) and scattering fraction (SF). The quality indicators of PET images included signal-to-noise ratio (SNR),the maximum SUV (SUVmax) of lesions,the tumor-to-background ratio (TBR),the contrast-to-noise ratio (CNR) and the visual scores of 18F-FDG PET/CT images on livers were evaluated. The differences and consistency of various indicators between DPR and OSEM reconstruction algorithms were further analyzed. Results:The average 18F-FDG PET/CT injection activity of 27 patients was (0.12±0.01) mCi (1 mCi=37 MBq)/kg,and the counting rate of true coincidence,NECR and SF of PET images were respectively (153.73±25.09),(44.81±8.47) kcps and (36.77±1.91)％. The SNR of liver obtained by DPR algorithm was (15.83±3.60),which was significantly higher than that (9.06±1.87) of OSEM algorithm,with statistically significant (t=20.6,P<0.05),and there was significantly correlation in liver SNR between two algorithms (R2=0.91,P<0.05). In 27 uptake 18F-FDG PET/CT lesions,the SUVmax,TBR and CNR of lesions that were obtained from OSEM algorithm were respectively (5.86±1.49),(1.95±0.49) and (17.74±4.77),which were lower than corresponding those of DPR algorithm,and the differences were significant (t=9.03,8.79,15.49,P<0.05),respectively. There were significant correlations in SUVmax,TBR and CNR between the two algorithms (R2=0.71,0.70,0.76,P<0.05),respectively. The visual scores of PET images obtained from the DPR algorithm was 4 (3,5) scores,which was significantly higher than 3 (2,4) scores of OSEM algorithm,and the difference of that between two algorithms was significant (U=396,P<0.05). Conclusion:The scattering effect of 18F-FDG PET/CT imaging is stronger in obese patients,whose counting rate of equivalent effect of noise is lower. The DPR reconstruction algorithm can significantly improve the SNR and lesion contrast of PET images than the OSEM algorithm,which has significant gain effect on the SUVmax of lesions,and it can significantly improve the quality of 18F-FDG PET/PET images in obese patients.