Abstract:Objective：To investigate the effect of activation of alpha 7 nicotinic acetylcholine receptors（α7-nAChRs）combined with calcium ion（Ca²⁺ ）on the odontogenic/osteogenic differentiation of lipopolysaccharide（LPS）-stimulated human dental pulp stem cells （DPSCs）. Methods：DPSCs were isolated and cultured，and surface marker expression of DPSCs was identified by flow cytometry. The effect of α7-nAChRs agonist PNU-282987 and Ca²⁺ on DPSCs proliferation were detected by CCK-8. The optimal concentration of PNU- 282987 to promote alkaline phosphatase（ALP）activity in DPSCs was determined through ALP activity and staining. E.coli lipoplysaccharide（LPS）was used to simulate inflammatory microenvironment stimulation of DPSCs. The expression of proteins：type Ⅰ collagen（COL-I），dentin sialoprotein（DSPP），osteopontin（OPN），ALP，runt-related transcription factor2（RUNX2），osterix（OSX）， as well as the gene expression（COL-I，DSPP，OPN，ALP，RUNX2，OSX）and mineralized matrix related to odontogenic/osteogenic differentiation was examined by Western blot，quantitative real-time polymerase chain reaction（RT-qPCR）and Alizarin red staining.Fura-2 AM was used to detect intracellular Ca²⁺ flux. Results：The CCK-8 assay showed that PNU-282987 at a concentration of less than 10 μmol/L had no inhibitory effect on cell proliferation，and this concentration significantly increased ALP activity in LPS-stimulated DPSCs. Ca²⁺ at a concentration of less than 2 mmol/L had no inhibitory effect on cell proliferation；Western blot and RT-qPCR experiments showed that the expression of osteogenic/osteogenic related proteins（COL-I，DSPP，OPN，ALP，RUNX2，OSX）， genes（COL-I，DSPP，OPN，ALP，RUNX2，OSX），and mineralized matrix formation in LPS-stimulated DPSCs were significantly upregulated after treated with PNU-282987 and Ca²⁺ ，with the most significant upregulation observed when the two were combined（P < 0.001）. Fura-2 AM Ca²⁺ probe results revealed an increase in intracellular Ca²⁺ in DPSCs. Conclusion：10 μmol/L PNU-282987 combined with 2 mmol/L Ca²⁺ can promote the odontogenic/osteogenic differentiation of LPS-stimulated DPSCs.

Abstract:Objective：To validate the stability，tissue specificity，and sensitivity of circulating miR-124 for detecting lead neurotoxicity，so as to provide a basis for the evaluation of lead neurotoxicity using circulating miR-124. Methods：A rat middle cerebral artery occlusion model was established using Zea-Longa line plug method. Blood samples were collected，centrifuged，and aliquoted，then immediately tested or stored at different times under conditions of room temperature，2 ℃ to 8 ℃，and -70 ℃ to -90 ℃ the expression of miR-124 was detected by RT-qPCR method. Hepatotoxicity，cardiotoxicity and nephrotoxicity models were established with acetaminophen（1 250 mg/kg），isoprenaline（2.5 mg/kg）and gentamycin（80 mg/kg），respectively. The expression of circulating miR -124 was detected and compared in the collected pre -modeling and post -modeling blood samples. Rat neurotoxicity models were established with lead acetate（300 and 600 mg/kg）. ELISA method was used to detect the changes of IL-10，IL-1β，and TNF -α. The sensitivity was evaluated by comparing the time of changes detected of cytokines and circulating miR-124. Results： Compared with fresh blood samples，circulating miR-124 remained stable when the blood samples were stored at room temperature for 6 h，at 2 ℃ to 8 ℃ for 24 h，at -70 ℃ to -90 ℃ for 36 d，and for three freeze-thaw cycles. The stability could support the requirement so flaboratory. Circulating miR-124 has good tissue specificity since no significant changes were noted in rat hepatotoxicity， cardiotoxicity and nephrotoxicity models. Compared with the cytokines，circulating miR-124 could evaluate neuroinflammation caused by lead exposure with a more sensitive manner. Conclusion：Circulating miR-124 has good stability，tissue specificity and sensitivity， and can be used as a potential biomarker of evaluating lead neurotoxicity.

Abstract:Objective：This study aimed to investigate the physicochemical properties of a three-dimensional（3D）composite scaffold loaded with curculigoside（CUR）and assess its potential impact on promoting angiogenesis and osteogenic induction in human umbilical vein endothelial cells（HUVEC）and mouse bone marrow mesenchymal stem cells（BMSC）. Methods：Polycaprolactone microspheres loaded with Curculigoside（CUR-PM）were prepared using an emulsion/solvent evaporation technique. We successfully engineered a 3D composite scaffold comprising hydroxyapatite（HA），gelatin（GEL），and sodium alginate（SA）with the assistance of 3D bioprinting technology，denoted as HGS. Furthermore，we established a polycaprolactone-based microsphere scaffold，referred to as HGSC，for the purpose of CUR loading. The scaffold was characterized by scanning electron microscopy，infrared spectroscopy， rheology，mechanical properties，drug release，and degradation experiments. The biocompatibility of the scaffold was verified using CCK-8 and EdU fluorescence staining experiments. The potential of the HGSC scaffold to promote cell vascularization and bone regulation was assessed through HUVEC tube formation experiments and alkaline phosphatase（ALP）staining. Results：The HGSC exhibited a uniform grid-like structure with appropriate mechanical properties and degradation compared to HGS. The CCK-8 and EdU fluorescence staining demonstrated excellent biocompatibility of the HGSC scaffold. The outcomes of HUVEC tube formation experiments and BMSC ALP staining provided evidence that the HGSC scaffold exhibited the potential in promoting angiogenesis and osteogenesis. Conclusion：The HGSC scaffold has shown excellent biocompatibility and has a clear promoting effect on the osteogenic potential of BMSC and angiogenesis of HUVEC. This study offers a promising therapeutic strategy for bone defect repair.

Abstract:Objective：To explore the potential mechanisms of Chouchunpi San（CCPS）on colorectal cancer based on cell experiments and network pharmacology. Methods：The targets of CCPS active compounds and colorectal cancer were screened by network pharmacology. The protein-protein interaction（PPI）network were constructed，and the potential targets of CCPS were predicted. Enrichment analysis was conducted to predict pathways through which CCPS may exert its anti-colorectal cancer effects. The effect of CCPS on the viability of colorectal cancer cells was detected by CCK-8 assay，and the effects of different concentrations of CCPS on apoptosis of colorectal cancer cells were detected by flow cytometry. Wounding-healing assay was employed to investigate the impact of CCPS on the migration capacity of colorectal cancer cells. The expression of STAT3 protein in colorectal cancer cells after CCPS induction was determined by Western blot. Results：There are 117 active components，920 potential targets，and 787 drug and disease intersection targets of CCPS were retrieved through the database. Protein-protein interaction（PPI）network analysis identified core targets such as STAT3，MAPK1，AKT1，and MYC.The results of GO enrichment and KEGG pathway analysis indicated that CCPS in mainly involved in biological processes relalted to cell apoptosis and oxidative stress response，and the pathways involved included cancer pathway，AGE-RAGE signaling pathway，and PI3K-Akt signaling pathway.Molecular docking results showed that STAT3 had a highly binding affinity with its core compound licochalcone A. Cell experiments demonstrated that CCPS inhibited the proliferation and migration capacity of colorectal cancer cells and significantly promoted cell apoptosis. Western blot results showed that the expression of STAT3 protein in cells significantly decreased after treatment with different concentrations of CCPS，and the decrease was concentration-dependent. Conclusion：This study revealed the multi-component，multi-target，and multi-pathway mechanisms of CCPS in the treatment of colorectal cancer. CCPS significantly inhibited the proliferation and migration capacity of colorectal cancer cells and its mechanism may be related to the targeted reduction of STAT3 protein levels.

Abstract:Objective：To investigate the effects and underlying mechanism of cryptotanshinone（CTS）on pulmonary fibrosis in rats with hyperoxia-induced bronchopulmonary dysplasia（BPD）. Methods：50 newborn male Sprague-Dawley rats were randomly divided into air group，hyperoxia group，low-dose CTS（7.5 mg/kg）group，medium-dose CTS（15.0 mg/kg）group and high-dose CTS（30 mg/kg） group. Rats in hyperoxia and three CTS treatment groups were exposed to 95% oxygen（O₂）for 7 d after birth，and the air group were exposed to a room environment（21% O₂）. 7 days later，all rats were euthanized. The alveolar morphology and lung fibrosis were evaluated using hematoxylin-eosin（HE）staining and Masson staining. The mRNA levels of transforming growth factor beta1（TGF-β1） and alpha-smooth muscle actin（α-SMA）were detected by RT-qPCR. The protein expression of cell signaling molecules small mother against decapentaplegic（Smad）2/3 and p -Smad2/3 was detected by Western blot. In vitro experiments：Human fetal lung fibroblasts （HFL-1）cells were selected and divided into air group，hyperoxia group and CTS intervention group according to the culture conditions. The air group was cultured under conventional conditions，while the hyperoxia and intervention groups were incubated in a 95% O₂ incubator for 24 h. 10 μmol/L CTS was added to the intervention group. Cell viability was measured by CCK-8 assay，and protein expression of TGF-β1，α-SMA，p-Smad2/3 and Smad2/3 were detected by Western blot. Results：Compared with the control group，rats in the hyperoxia group had disorderd alveolar morphology，widened alveolar septa，decreased RAC values and increased fibrosis scores（P < 0.05）；increased the mRNA levels of TGF-β1 and α-SMA（P < 0.05）；and up-regulated p-Smad2/3 expression（P < 0.05）. Different doses of CTS could improve the above indicators（P < 0.05）. Meanwhile，CTS also reduced TGF-β1，α-SMA，p-Smad2/ 3，and Smad2/3 protein expression levels in HFL-1 cells after hyperoxia（P < 0.05）. Conclusion：CTS ameliorates the fibrotic process of hyperoxia-induced lung injury via the TGF-β/Smad pathway.

Abstract:Objective：To evaluate the application value of early subclinical myocardial damage in patients with long COVID using two-dimensional speckle tracking imaging（2D-STI）technology. Methods：Fifty-nine patients with post-COVID infection after the unsealing of the COVID epidemic in China on December 7，2022 were enrolled as the observation group，and 60 pre-epidemic healthy people who were screened in the out patient department were selected as the healthy control group. Basic clinical data，markers of myocardial injury and other laboratory indicators of patients were collected. Two-dimensional echocardiography and 2D-STI were used to evaluate left ventricular ejection fraction（LVEF），left ventricular diastolic function（E/A，E/e’），global longitudinal strain（GLS）， and segmental strain values，and the heart rate，LVEF，E/A，E/e’，GLS，and segmental strain values were calculated and compared between the groups. Results：The study found that the left ventricular diastolic function E/A（1.14±0.34 vs. 1.46±0.44，P<0.001），E/e’ （8.01±2.08 vs. 7.21±1.53，P<0.05），and GLS［（-20.57±2.15）% vs.（-21.90±1.73）%，P<0.001］of patients with long COVID syndrome were significantly decreased compared to healthy control individuals. Further segmental strain analysis revealed significant decreases in ten segments，including basal anteroseptal，mid anterior，mid anteroseptal，mid inferolateral，mid anterolateral，apical anterior，apical anteroseptal，apical inferior，apical inferolateral and apical anterolateral in the COVID group（P<0.05）. Subgroup analysis based on post-infection time found that as the recovery time from COVID prolonged，the GLS of patients showed a gradual improvement trend. Conclusion：Patients after COVID infection often experience a decrease in left ventricular diastolic function and GLS. With the prolongation of COVID recovery time，the above indicators show a gradual improvement trend. The application of 2D-STI technique can quantitatively evaluate early subclinical myocardial injury in patients with long novel coronavirus syndrome，which may provide evidence for clinical diagnosis and treatment of COVID patients.

Abstract:Objective：To evaluate the feasibility of interventional closure in migraine patients with moderate right -to -left shunt patent foramen ovale（RLS-PFO）by comparing the surgical difficulty and short-term efficacy between patients with moderate or large RLS-PFO. Methods：A total of 95 patients with migraine accompanied by moderate or large RLS-PFO who underwent interventional closure were selected. The differences inmigraine symptoms，closure success rate，closure difficulty，postoperative RLS volume and postoperative headache relief level were analyzed. Results：There was no significant difference in preoperative headache impact test-6 （HIT-6）and migraine disability assessment questionnaire（MIDAS）scores between the two groups（P＞0.05）. There was no difference in closure success rate between the two groups（92.00% vs. 98.57%，P=0.137），but the usage rate of the second guidewire，intracardiac ultrasound utilization rate，and X-ray exposure time were significantly higher in the moderate RLS-PFO group than in the large RLS- PFO group（P < 0.01）. The effective closure rate at 3 days after the procedure was higher in the moderate RLS-PFO group than in the large RLS-PFO group（86.96% vs. 56.52%，P=0.008），but there were no differences in RLS volume and effective closure rate at 1 month，3 months and 6 months after operation between the two groups（P＞0.05）. The HIT-6 and MIDAS scores were improved at 6 months after the procedure compared to before the procedure in both groups（P<0.001），but the decrease in HIT-6 score at 6 months after the procedure was smaller in the moderate RLS-PFO group than in the large RLS-PFO group（P=0.012），while there was no difference in MIDAS score. Conclusion：The surgical difficulty of interventional closure in migraine patients with moderate RLS-PFO is higher than in patients with large RLS-PFO，but the efficacy of headache relief after interventional closure is similar between the two groups.

Abstract:Objective：To explore the genetic alterations and metabolite changes in pediatric acute lymphoblastic leukemia（ALL）. Methods：From September 2021 to May 2022，4 children with ALL who were treated for the first time in the Department of Pediatrics of the First Affiliated Hospital of Nanjing Medical University were selected as the experimental group，and 4 healthy children who underwent physical examination in this hospital at the same time were selected as the control group. Clinical data and serum samples were collected. Serum metabolite profiling was performed by liquid chromatography-mass spectrometry，and genetic variations were analyzed by exome sequencing. Results：Metabolomics revealed that 61 metabolites have difference，with 37 showing increased expression in ALL. The most significant upregulated metabolites were identified as cresol and deoxycholic acid. Additionally，24 metabolites exhibited decreased expression，with 1-pyrroline-5-carboxylic acid and serotonin，etc.，being the most significantly downregulated metabolites. Exonomics has revealed that among the top ten genes ranked by protein interactions include MUC17. Conclusion：There are obvious differences in serum metabolites between children with ALL and healthy children，involving a variety of metabolic pathway changes，and the differential metabolites identified are of great significance for the diagnosis and treatment of ALL. Exome sequencing suggests that genes such as MUC17 may play a certain role in the occurrence of ALL，providing novel concepts and approaches for the study and clinical pharmacotherapy of ALL.

Abstract:Objective：To investigate the safety and efficacy of thoracic endovascular aortic repair（TEVAR）in patients with stent induced new entry（SINE）in the distal aortic dilation following surgical repair of type A aortic dissection（TAAD）. Methods：A retrospective analysis was performed on 27 consecutive patients who underwent TEVAR for stent graft-induced distal aortic dilation in Nanjing Medical University First Affiliated Hospital from January 2018 to March 2023. The intraoperative data of 27 patients with Sun’s surgery（total aortic arch replacement plus stented elephant trunk implantation），early postoperative follow-up results of Sun’s surgery， intraoperative data of 27 patients with TEVAR and postoperative follow-up results were statistically analyzed. Results：The follow-up rate after TEVAR was 92.3%，with a mean follow-up time of（35±21）months. There were two cases of long-term mortality，resulting in a mortality rate of 7.4%，with no deaths related to aortic complications. No stent graft leak，displacement，paraplegia，new-onset dialysis （post-TEVAR new-onset renal dysfunction），intestinal ischemia，or necrosis was observed after TEVAR. Among the follow-up cases， preoperative and postoperative computed tomographic angiography（CTA）of the thoracoabdominal vessels were successfully obtained in 25 cases（92.3%）. At 6 months postoperatively，CTA revealed that the rupture was completely covered，the distal true cavity opening of the thoracic aorta was satisfactory，and the vascular patency of the internal organs and lower limbs was 100% . 19 patients were followed up 1 year after surgery. Among them，there were 13 cases（68.4%）of complete thrombolysis and 6 cases（31.6%）of partial thrombolysis，the true lumen was effectively opened，the true lumen of the stent covered area was significantly enlarged，and the false lumen was reduced. Conclusion：TEVAR treatment of distal aorta after acute type A aortic dissection is effective without significant adverse events，making it a recommended surgical approach .

Abstract:Objective：To explore the clinical application effects of del Nido and histidine-tryptophan-ketoglutarate（HTK） cardioplegia in patients with left ventricular hypertrophy（LVH）undergoing open-heart surgery. Methods：A total of 75 LVH patients who underwent cardiopulmonary bypass（CPB）surgery in our hospital from January 2021 to December 2022 were retrospectively collected and were divided into del Nido group（group D，39 cases）and HTK group（group H，36 cases）according to the type of cardioplegia used during open-heart surgery. General information，interoperative anesthesia and cardiopulmonary bypass data， postoperative clinical information，and changes in perioperative myocardial markers were compared between the two groups. Results： After releasing aortic cross-clamp（ACC），the incidence of ventricular fibrillation（VF）was lower in the group D than in the group H （P< 0.01）. Among patients with VF，the duration of VF，defibrillation times，and defibrillation energy were lower in the group D than in the group H（P< 0.05）. The group D had a longer time for spontaneous heart rhythm recovery than the group H（P< 0.05），and the temporary pacemaker usage rate was higher in the group D than in the group H（P< 0.05）.The group D had a higher vasoactive-inotropic score（VIS）score 15 minutes after the end of CPB than the group H（P< 0.001），while there was no significant difference in VIS scores between the two groups 15 minutes before the end of the operation and 6 hours after the operation（P > 0.05）. In terms of myocardial markers，only at 24 hours after surgery，the levels of creatine kinase isoenzymes-MB（CK-MB）and cardiac troponin T（cTnT） were higher in the group H than in the group D（P< 0.05）；there was no significant difference in myocardial markers between the two groups at 48 hours after surgery（P > 0.05）. Conclusion：Both del Nido and HTK cardioplegia can be safely used for myocardial protection in patients with LVH during surgery. However，the use of HTK cardioplegia is associated with a higher incidence of VF after ACC removal and higher levels of CK-MB and cTnT at 24 hours after surgery compared to del Nido cardioplegia. On the other hand，the use of del Nido cardioplegia is associated with a longer time to recovery of spontaneous heart rhythm，a higher temporary pacemaker usage rates，and a higher doses of vasoactive drugs at 15 minutes after ACC removal compared with HTK cardioplegia.

Abstract:Objective：To investigate the value of a model based on multi -parameter magnetic resonance imaging（MRI）radiomics features in predicting the expression status of human epidermal growth factor receptor-2（HER -2）in invasive breast cancer patients. Methods：A retrospective analysis was conducted on baseline MRI images and clinical data of 401 breast cancer patients from January 2018 to December 2019 at the First Affiliated Hospital of Nanjing Medical University. The 2D region of interest（ROI）were segmented manually on ITK-SNAP software at the maximum tumor level of turbo inversion recovery magnitude（TIRM），dynamic-contrast enhanced magnetic resonance imaging phase 2（DCE2），dynamic -contrast enhanced magnetic resonance imaging phase 4（DCE4）， diffusion-weighted imaging（DWI）and apparent diffusion coefficient（ADC）. Feature extraction and dimensionality reduction screening were performed on the delineated ROIs. Logistic regression（LR）algorithm was used to construct single-parameter，combination and multi-parameter models for predicting HER-2 expression status. Results：A total of 26 optimal radiomics features were selected，with DCE2_original_shape_SurfaceVolumeRatio ranking first in terms of weight. Among the single-parameter models，the DCE2 model showed the best prognostic efficacy（AUC values of 0.907 and 0.879 for the training and test sets，respectively）. Among the combined models，the combined with DCE model had better predictive performance than the models without DCE（all P values ≤0.001）. The multi-parameter model had the best predictive performance（AUC values of 0.932 and 0.906 for the training and test sets， respectively）. Conclusion：The radiomics model based on multi-parameter radiomics features has certain clinical value in evaluating the HER-2 expression status in invasive breast cancer，with higher predictive value for early enhancement features.

Abstract:Objective：To predict the risk of initial esophageal variceal bleeding in patients with liver cirrhosis accompanied by esophageal varices. Methods：Clinical data of patients diagnosed with liver cirrhosis accompanied by esophageal varices at the First Affiliated Hospital of Nanjing Medical University from January 2016 to March 2019 were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to determine the independent prognostic factors for the occurrence of initial esophageal variceal bleeding in patients with liver cirrhosis and esophageal varices. R software was used to construct the nomogram model. Receiver operating characteristic（ROC）curve was used to assess the prediction ability of the nomogram model. Bootstrap method was used for in-model validation and concordance index（C-index）was calculated to evaluate the discrimination of the model. Calibration curve was plotted to assess the calibration of the model. Results：The maximum diameter of esophageal varices，spleen longitudinal diameter，and total bilirubin（TBIL）were independent risk factors for the occurrence of initial esophageal variceal bleeding in patients with liver cirrhosis and esophageal varices. Based on this，a nomogram prediction model was constructed，with an area under the ROC curve（AUC）of 0.918 for no initial bleeding within 1 year and an AUC of 0.893 for no initial bleeding within 2 years. After internal verification，the C-index of the model was 0.852. The calibration curve shows good consistency between the nomogram prediction results and actual results. Conclusion：The maximum diameter of esophageal varices and TBIL have good predictive value of the occurrence of initial variceal bleeding in patients with liver cirrhosis and esophageal varices. The prediction model based on the three indicators of the maximum diameter of esophageal varices，spleen longitudinal diameter，and TBIL has good discrimination and accuracy.

Abstract:Objective：To describe the preparation process of domestic carrier -free lutetium［¹⁷⁷Lu］and the method for labeling of ¹⁷⁷Lu with 1，4，7，10-tetraazacyclododecane-1u-，4，7，10-tetraacetic acid conjugated Tyr3-octreotide（DOTA-TOC），and to explore the safety and efficacy of the preliminary clinical application of domestically produced ¹⁷⁷Lu-DOTA-TOC. Methods：Domestic carrier-free lutetium［¹⁷⁷Lu］was prepared by multistage sequential isolation and purification，and fully automated modular labeling was used to synthesize ¹⁷⁷Lu -DOTA -TOC. The data of 4 patients with neuroendocrine neoplasms（NEN）in Naning Hospital Affiliated to Nanjing Medical University who only received domestic carrier-free lutetium［¹⁷⁷Lu］labeled DOTA-TOC peptide receptor radionuclide therapy （PRRT）were retrospectively analyzed. Results：The domestic carrier-free lutetium［¹⁷⁷Lu］had good quality control，with copper（Cu）< 0.01，zinc（Zn）<0.01，iron（Fe）<0.01，lead（Pb）<0.15，and thulium（Yb）undetectable，radiochemical purity >99%，and bacterial endotoxin <2 EU/mL. The yield of domestic automated labeling of ¹⁷⁷Lu-DOTA-TOC was（98.85±0.97）%，and the specific activity of the product was（80.96 ± 7.47）GBq/μmol. Sterility and endotoxin tests of the labeled product met the specified standards，and the ethanol content in the labeled product was 0，with a radiochemical purity greater than 99%. Among the 4 patients who received only domestic ¹⁷⁷Lu-DOTA-TOC only，1 patient showed almost complete disappearance of the primary and metastatic lesions after only one treatment，while another patient experienced grade 3 bone marrow toxicity one month after treatment，which recovered to normal after three months. None of the patients showed renal toxicity. Conclusion：Domestic carrier-free lutetium［¹⁷⁷Lu］labeled DOTA-TOC meets quality control standards，has a high yield，good safety，and tolerability，and has good therapeutic efficacy for patients with inoperable NEN. The domestication and large-scale production of carrier-free lutetium［¹⁷⁷Lu］will promote the integrated development of nuclear medicine diagnosis and treatment in China.

Abstract:Objective：To analyze the technical key points of short-term high cervical spinal cord electrical stimulation in the treatment of severe consciousness disorders in patients with brain injury and clinical diagnostic and therapeutic value of this procedure. Methods：A retrospective analysis was conducted on 10 cases of short -term high cervical spinal cord stimulation performed at the Department of Neurosurgery，the First Affiliated Hospital of Nanjing Medical University from June to September 2023. The technical key points of the surgical process were analyzed，and the clinical application value was evaluated through follow-up analysis. Results： Under general anesthesia，with the patient in the prone position，a percutaneous puncture of the thoracic 8 intervertebral space was performed to access the extradural space，and under X-ray fluoroscopy，the top of the spinal cord stimulation electrode was successfully placed at the level of C2. Stimulation therapy was conducted for 2-3 week，with stimulation parameters selected as follows：frequency 5/ 70 Hz，voltage 1-5V，small stimulation cycle：on for 15 min，off for 15 min，large stimulation cycle：on at 08：00 am，off at 20：00 pm. Follow-up was conducted at 4 weeks post-surgery，with 1 out of 8 patients in a vegetative state（VS）reaching a minimally conscious state （MCS）+，5 patients remaining MCS-，and 2 patients still in a VS status. Among the 2 patients who were MCS- preoperatively，1 patient recovered from a MCS，and 1 patient reached MCS+，with no surgery-related complications observed in either case. Conclusion：Short- term high cervical spinal cord stimulation is minimally invasive，safe and effective，with short-term therapeutic and diagnostic value. It has broad prospects for application in the diagnosis and treatment of consciousness disorders. Attention should be paid to the specific difficulties and technical aspects of electrode placement during the surgical procedure.

Abstract:Objective：To explore the experience of liver re-transplantation for chronic graft failure. Methods：A retrospective analysis was conducted on 4 patients who underwent re-transplantation for chronic graft dysfunction in our team from January 2019 to December 2020，focusing on surgical time，intraoperative blood transfusion volume，ICU stay，total hospital stay，postoperative complications，and a literature review was conducted to summarize the experience of re-transplantation. Results：The surgery of all four patients were successful，using the in situ classic liver transplantation procedure，with an average operation time of 420 min（385-480 min），an average intraoperative infusion of 11.5 U of red blood cells（8-16 U），and an average of 1 350 mL of fresh frozen plasma （1 000-2 075 mL）. The average ICU stay after surgery was 3 days（2-4 days），and an average postoperative hospitalization of hospital stay after surgery was 21 days（14-31 days）. Among the 4 patients，3 had no significant complications during hospitalization. 1 patient developed stenosis of the inferior vena cava and was cured after percutaneous balloon dilation. Regular follow-up after discharge has shown stable conditions in 3 cases，while 1 patient died 20 months after surgery due to non-ischemic biliary disease. Conclusion：Liver re-transplantation is the only effective treatment for chronic graft failure after liver transplantation. By selecting suitable cases， improving surgical techniques，and enhancing perioperative management，better therapeutic effects are expected to be achieved.

Abstract:Objective：To explore the feasibility of using ResNet+VST model based on deep learning（DL）for intelligent detection of key frames in echocardiography. Methods：A total of 663 dynamic images including apical two chambers（A2C），apical three chambers （A3C），and apical four chambers（A4C），which are commonly used clinical examination views，were collected from the Department of Ultrasound Medicine at Drum Tower Hospital，Nanjing University Medical School. Additionally，280 dynamic A4C images from the EchoNet-Dynamic public dataset were selected. Two datasets were established：the Nanjing Drum Tower Hospital dataset and the EchoNet-Dynamic-Tiny dataset. The images in each category were divided into training set and testing sets in a 4：1 ratio. The ResNet+ VST model was trained and its performance was compared with other key frame detection models to verify the its superiority. Results： The ResNet+VST model can detect the end-diastolic（ED）and end-systolic（ES）image frames of the heart more accurately. On the Nanjing Drum Tower Hospital dataset，the model achieved ED frame prediction differences of 1.52±1.09，1.62±1.43，and 1.27±1.17 for A2C，A3C，and A4C views，respectively，and ES frame prediction differences of 1.56±1.16，1.62±1.43，and 1.45±1.38，respectively. On the EchoNet-Dynamic-Tiny dataset，the model achieved an ED frame prediction difference of 1.62±1.26 and an ES frame prediction difference of 1.71 ± 1.18，outperforming existing related studies. Furthermore，the ResNet + VST model exhibited good real-time performance，with average inference times of 21 ms and 10 ms for 16-frame ultrasound sequences on the Nanjing Drum Tower Hospital dataset and the EchoNet -Dynamic -Tiny dataset，respectively，using the GTX 3090Ti GPU. This performance was superior to related studies that used long short -term memory（LSTM）for temporal modeling and met the requirements for clinical real -time processing. Conclusion：The proposed ResNet + VST model demonstrates superior accuracy and real-time performance in the detection of key frames in echocardiography compared to existing research. In principle，this model can be applied to any ultrasound view and has the potential to assist ultrasound physicians in improving diagnostic efficiency.

Abstract:Peptides are bioactive substances involved in various cellular functions in the human body，mainly derived from two pathways：amino acid dehydration condensation and protein degradation. All cells can synthesize peptide substances，and cell function activities are also regulated by peptides. Peptidomics based on mass spectrometry has been applied in disease diagnosis and treatment. A few related studies have also begun to explore the pathogenesis of gynecological and obstetric diseases，such as ovarian cancer， preeclampsia，gestational diabetes mellitus，cervical cancer，endometriosis，etc. Therefore，it is of great clinical significance to study peptidomics to explore the potential pathogenesis and biomarkers of these obstetrics and gynecology diseases.

Abstract:The prognosis of patients with myelodysplastic neoplasms（MDS）is closely linked to their cytogenetic and molecular genetic characteristics. Among the most prevalent genetic mutations in MDS，the TP53 gene abnormalities stand out as an independent adverse prognostic factor for MDS and a significant risk factor for the progression to acute myeloid leukemia（AML）. The recently updated 5th edition of the WHO classification of haematolymphoid tumours（WHO 2022）and international consensus classification of myeloid neoplasms and acute leukemia（ICC）recognizes MDS with TP53 biallelic inactivation（biTP53）as a distinct and independent subtype. Patients within this subtype face an exceedingly grim prognosis with an extremely short survival period. Currently，available treatments for MDS patients with TP53 gene abnormalities have proven ineffective in improving their prognosis. Consequently，there is a growing focus on exploring new avenues such as targeted therapies and immunotherapy. This article provides an in-depth review of the progress in clinical research related to MDS with TP53 gene abnormalities，both within domestic and international contexts.

Abstract:Thyroid hormone metabolites，as important regulators of physiology and pathology，have received more and more attention. In addition to having similar effects to thyroid hormones in modulating hyperglycemia，improving dyslipidemia and promoting brain development，researchers have also found that they play an important role in protecting the heart from myocardial ischemia reperfusion injury and inhibiting the proliferation of tumor cells. Further investigations of thyroid hormone metabolites are needed to fully reveal their physiological actions and mechanisms，and this may open new perspectives for the treatment of metabolic diseases， neurological diseases and cancer.

Abstract:With the innovative development of histone deacetylase inhibitors（HDACi），a class of drugs targeting epigenetic regulation mechanism，the treatment landscape for breast cancer patients is gradually changing. Both hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer patients，as well as triple-negative breast cancer（TNBC）patients，can benefit significantly from combination therapy with HDACi. This article summarizes the research progress of HDACi in various molecular subtypes of breast cancer，with a particular focus on the treatment status in the Chinese population and exploration of rational combination therapy strategies in the future.

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