Objective:To construct and evaluate the predictive performance of a multiphase ultrasound radiomics model for microvascular invasion（MVI）in hepatocellular carcinoma（HCC）.Methods:A total of 126 patients with pathologically confirmed HCC were retrospectively enrolled from 4 medical centers between May 2018 and July 2025，including the First Hospital of Shanxi Medical University，Shanxi Province Third People's Hospital，Changzhi People's Hospital，and the Organ Transplant Center of the Affiliated Hospital of Qingdao University. A total of 630 ultrasound images of the lesions in different phases were collected，from which 1 561 radiomic features were extracted. The patients from medical institutions in Shanxi Province were chosen as the training set（ n=91），and the patients from the Organ Transplant Center of the Affiliated Hospital of Qingdao University were chosen as the validation set（ n=35）. In the training set，37.4%（34/91）patients presented MVI（+），whereas in the validation set，54.3%（19/35）patients presented MVI（+）. Radiomics features were extracted from ultrasound images，and features related to the MVI（+）were selected through dimensionality reduction analysis. Five multiple machine learning algorithms were used to construct predictive models，which were then evaluated using an external validation set. The Radscore was calculated，and a nomogram was constructed combining Radscore with ultrasound and clinical characteristics to predict MVI. Results:The model combining radiomics features from the portal venous phase and the delay phase showed the best predictive performance in both the training and validation sets，with area under curve（AUC）values of 0.835 and 0.727，respectively. The prediction model developed using radiomics Radscore and clinical indicators could be represented and presented as a nomogram.Conclusions:The radiomics model based on multi-phase ultrasound offers a novel approach for non-invasive preoperative prediction of MVI in liver cancer. Furthermore，its integration with clinical features aids in optimizing clinical treatment strategies.

Objective:To prepare novel targeted lipid nanobubbles（MEB-NBs）that can be loaded with exosomes（Exo），and test the property and explore the specific invitro target-seeking ability of MEB-NBs. Methods:The core lipid nanobubbles（NBs）were prepared using mechanical oscillation methods，and Exo was connected to the NBs through membrane fusion. The target antibody MYH6 was linked to the NBs using a phospholipid coupling covalent method，resulting in the preparation of targeted lipid nanobubbles MEB-NBs loaded with Exo. The morphology，particle size，and surface potential of the prepared lipid nanobubbles MEB-NBs were observed，and the co-loading of Exo and NBs was verified using laser confocal and fluorescence resonance energy transfer techniques. The in vitro imaging capability and biosafety of MEB-NBs were evaluated，and the loading rate and drug content of Exo carried by MEB-NBs were measured. The ability of MEB-NBs to specifically target hiPSC-CMs cells was observed using flow cytometry，small animal in vivo imaging systems，and laser confocal microscopy. Results:The average particle size of the prepared MEB-NBs was（597.10 ± 47.70）nm，the surface potential was（-11.70 ± 0.21）mV，and the concentration was（2.43 ± 0.06）×10 7/ml. Laser confocal microscopy and FRET results confirmed that the Exo was effectively connected with the NBs；When the Exo concentration was 250 μg/ml，the Exo loading rate and drug loading of MEB-NBs were both 73.8%，and the results of laser confocal microscopy showed that MEB-NBs could be effectively targeted to hiPSC-CMs cells. MEB-NBs were well developed in vitro and had good biological safety. Conclusions:This study constructs novel Exo-loaded targeted lipid nanobubbles（MEB-NBs）that demonstrate stable physicochemical properties and ultrasound imaging capabilities. The developed MEB-NBs precisely target hiPSC-CMs cells，providing an innovative drug delivery system with enhanced therapeutic efficacy for Exo-based therapies.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective To evaluate the clinical efficacy and safety of Jiangzhi Hugan Soft Extract(composed of stir-fried Dioscoreae Rhizoma,Poria,Ginseng Radix et Rhizoma,Bupleuri Radix,Citri Sarcodactylis Fructus,Persicae Semen,Polygoni Cuspidati Rhizoma,etc.)in treating non-alcoholic fatty liver disease(NAFLD)with internal dampness-turbidity accumulation syndrome.Methods Sixty patients with NAFLD of dampness-turbidity accumulation syndrome treated at the Gastroenterology Department of Maoming Hospital of Guangzhou University of Chinese Medicine(Maoming Hospital of Traditional Chinese Medicine)from November 2023 to December 2024 were enrolled.The patients were divided into trial group and control group using stratified randomization,with 30 patients in each group.Both groups received lifestyle interventions(diet control and exercise),with the trial group additionally receiving Jiangzhi Hugan Soft Extract for 4 weeks.Outcomes included body mass index(BMI),liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT)],lipid profiles[total cholesterol(TC),triglycerides(TG)],traditional Chinese medicine(TCM)syndrome scores,efficacy evaluation,and safety assessment.Results(1)After 4 weeks of treatment,the overall response rate in the trial group was 93.33％(28/30),while that in the control group was 60.00％(18/30).The intergroup comparison(by rank sum test)showed that the efficacy of TCM syndrome in the trial group was significantly superior to that in the control group,with a statistically significant difference(P＜0.01).(2)After treatment,the BMI of patients in both groups was improved significantly compared to before treatment(P＜0.01).The improvement in BMI was significantly greater in the trial group than in the control group.The difference in the change of BMI between the two groups was statistically significant before and after treatment(P＜0.05).(3)After treatment,the levels of ALT,AST,and GGT in both groups decreased compared to before treatment(P＜0.01).The trial group showed a significantly greater reduction in ALT,AST,and GGT levels than the control group.The difference between the two groups was statistically significant before and after treatment(P＜0.05).(4)After treatment,both groups showed a significant decrease in TC and TG levels compared to pre-treatment levels(P＜0.05).The trial group demonstrated a more pronounced reduction in TC levels than the control group.The difference between the two groups was statistically significant before and after treatment(P＜0.05).(5)There were no significant adverse reactions occurring in either group during treatment,indicating a high level of safety.Conclusion Jiangzhi Hugan Soft Extract effectively improves BMI,liver function,and lipid profile in NAFLD patients with dampness-turbidity accumulation syndrome,demonstrating good clinical efficacy and high safety,warranting further clinical application.

Objective:To construct and evaluate the predictive performance of a multiphase ultrasound radiomics model for microvascular invasion（MVI）in hepatocellular carcinoma（HCC）.Methods:A total of 126 patients with pathologically confirmed HCC were retrospectively enrolled from 4 medical centers between May 2018 and July 2025，including the First Hospital of Shanxi Medical University，Shanxi Province Third People's Hospital，Changzhi People's Hospital，and the Organ Transplant Center of the Affiliated Hospital of Qingdao University. A total of 630 ultrasound images of the lesions in different phases were collected，from which 1 561 radiomic features were extracted. The patients from medical institutions in Shanxi Province were chosen as the training set（ n=91），and the patients from the Organ Transplant Center of the Affiliated Hospital of Qingdao University were chosen as the validation set（ n=35）. In the training set，37.4%（34/91）patients presented MVI（+），whereas in the validation set，54.3%（19/35）patients presented MVI（+）. Radiomics features were extracted from ultrasound images，and features related to the MVI（+）were selected through dimensionality reduction analysis. Five multiple machine learning algorithms were used to construct predictive models，which were then evaluated using an external validation set. The Radscore was calculated，and a nomogram was constructed combining Radscore with ultrasound and clinical characteristics to predict MVI. Results:The model combining radiomics features from the portal venous phase and the delay phase showed the best predictive performance in both the training and validation sets，with area under curve（AUC）values of 0.835 and 0.727，respectively. The prediction model developed using radiomics Radscore and clinical indicators could be represented and presented as a nomogram.Conclusions:The radiomics model based on multi-phase ultrasound offers a novel approach for non-invasive preoperative prediction of MVI in liver cancer. Furthermore，its integration with clinical features aids in optimizing clinical treatment strategies.

Objective:To prepare novel targeted lipid nanobubbles（MEB-NBs）that can be loaded with exosomes（Exo），and test the property and explore the specific invitro target-seeking ability of MEB-NBs. Methods:The core lipid nanobubbles（NBs）were prepared using mechanical oscillation methods，and Exo was connected to the NBs through membrane fusion. The target antibody MYH6 was linked to the NBs using a phospholipid coupling covalent method，resulting in the preparation of targeted lipid nanobubbles MEB-NBs loaded with Exo. The morphology，particle size，and surface potential of the prepared lipid nanobubbles MEB-NBs were observed，and the co-loading of Exo and NBs was verified using laser confocal and fluorescence resonance energy transfer techniques. The in vitro imaging capability and biosafety of MEB-NBs were evaluated，and the loading rate and drug content of Exo carried by MEB-NBs were measured. The ability of MEB-NBs to specifically target hiPSC-CMs cells was observed using flow cytometry，small animal in vivo imaging systems，and laser confocal microscopy. Results:The average particle size of the prepared MEB-NBs was（597.10 ± 47.70）nm，the surface potential was（-11.70 ± 0.21）mV，and the concentration was（2.43 ± 0.06）×10 7/ml. Laser confocal microscopy and FRET results confirmed that the Exo was effectively connected with the NBs；When the Exo concentration was 250 μg/ml，the Exo loading rate and drug loading of MEB-NBs were both 73.8%，and the results of laser confocal microscopy showed that MEB-NBs could be effectively targeted to hiPSC-CMs cells. MEB-NBs were well developed in vitro and had good biological safety. Conclusions:This study constructs novel Exo-loaded targeted lipid nanobubbles（MEB-NBs）that demonstrate stable physicochemical properties and ultrasound imaging capabilities. The developed MEB-NBs precisely target hiPSC-CMs cells，providing an innovative drug delivery system with enhanced therapeutic efficacy for Exo-based therapies.

Objective:To evaluate the application value of extended latissimusdorsi musculocutaneous flap combined with breast precision hand in stage Ⅰ breast reconstruction.Methods:Twelve cases of extended latissimusdorsi musculocutaneous flap combined with stage Ⅰ breast reconstruction for breast cancer precision surgery were collected from January 2022 to February 2023 in our department, the postoperative complications of surgical techniques were analyzed, and the cosmetic effects of breast reconstruction were evaluated according to Harris standards.Results:All 12 cases underwent breast reconstruction with extended latissimusdorsi musculocutaneous flap, and the survival rate of the flap was 100%. There was local cutaneous margin necrosis in 1 case of back incision, partial ischemic necrosis of the nipple in 1 case, and effusion in the donor area of the back in 5 cases. Harris evaluation of cosmetic effect of breast reconstruction was excellent in 3 cases, good in 6 cases, and fair in 3 cases. Follow-up time was 4-16 months (median was 12 months), and no local recurrence or distant metastasis was observed during follow-up.Conclusions:The extended latissimusdorsi musculocutaneous flap combined with precision mastectomy stage Ⅰ reconstruction is a safe and feasible treatment method for breast cancer.

Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.