Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

Objective To investigate the clinical effect and safety of bronchial arterial chemoembolization(BACE)combined with micro wave ablation(MW A)and immunotherapy in treating patients with advanced lung squamous cell carcinoma.Methods The clinical data of 68 patients with advanced lung squamous cell carcinoma,who were admitted to the North Jiangsu People's Hospital of China from June 2020 to June 2022 to receive treatment,were retrospectively analyzed.According to the therapeutic method,the patients were divided into control group(n=30,receiving BACE combined with immunotherapy)and observation group(n=38,receiving BACE followed by MW A,which was performed with CT-guided localization of the lung lesion,and immunotherapy in 3-5 days after BACE).Results The surgical success rate in both the 30 patients of the observation group and the 38 patients of the control group was 100％.After treatment,no surgery-related or chemoembolization-related serious complications occurred in both groups.In the control group and the observation group,the mean progression-free survival(PFS)was(5.70±1.61)months and(12.10±0.72)months respectively,the mean overall survival(OS)was(11.80±1.10)months and(13.00±1.13)months respectively.The PFS of the observation group was obviously longer than that of the control group(P＜0.05),and no statistically significant difference in OS existed between the two groups(P=0.255).Conclusion BACE combined with MW A and immunotherapy can effectively control the advanced lung squamous cell carcinoma,it has reliable short-term efficacy when compared with BACE plus immunotherapy,and it can inhibit tumor growth and prolong the PFS of patients,with a trend of extending OS and a satisfactory clinical safety.

Objective To investigate the safety and efficacy of super-selective arterial embolization in the treatment of abdominal wall hematoma.Methods The clinical data of 11 patients with abdominal wall hematoma,who were admitted to the Northern Jiangsu People's Hospital of China from January 2018 to December 2023,were retrospectively analyzed.All patients received angiography together with super-selective arterial embolization.The effectiveness of embolization treatment was evaluated by the technical success rate and therapeutic effect,and the safety was evaluated by the incidence of complication.Results The median age of the 11 patients was 70 years,91％were female,with a body mass index(BMI)of 25.1 kg/m2,subcutaneous fat thickness of 2.8 cm,and international normalized ratio(INR)of 1.12.DSA showed that 8 patients(72％)had active bleeding signs,3 patients(28％)had no active bleeding signs.Under DSA,a total of 18 responsible vessels,including 6 lumbar arteries(33.3％),5 deep circumflex iliac arteries(27.7％),5 inferior epigastric arteries(27.7％)and 2 iliolumbar arteries(11.3％),were identified and were treated with embolization.The median time spent for operation was 80 minutes.The technical success rate was 100％and the clinical effective rate was 91％.No operation-related major complications occurred,and the median hospital stay was 6 days.Conclusion For the abdominal wall hematoma in aged,obesity patients with underlying diseases,super-selective arterial embolization is a therapeutic method with high technical success rate,high clinical effective rate and satisfactory clinical safety.

Objective To discuss the clinical efficacy of microwave ablation(MWA)combined with percutaneous vertebroplasty(PVP),radiofrequency ablation(RFA)combined with PVP,and simple PVP in the treatment of vertebral metastatic tumors.Methods A total of 65 patients with vertebral metastatic tumors,who were admitted to the Northern Jiangsu People's Hospital of China to receive treatment from January 2019 to June 2023,were enrolled in this study.The patients were divided into MWA plus PVP group(M+P group,n=25,27 diseased vertebral bodies in total),RFA plus PVP group(R+P group,n=20,23 diseased vertebral bodies in total),and simple PVP group(P group,n=20,24 diseased vertebral bodies in total).Visual analog scale(VAS)score was used to assess the preoperative pain degree and the postoperative relief degree.Bone cement distribution and leakage at one week after surgery were evaluated.Results Successful operation was accomplished in all of the patients.No serious procedure-related complications occurred in all the patients of three groups.In R+P group,P group and M+P group,the preoperative mean VAS scores were(8.48±0.80)points,(8.57±0.98)points and(8.20±1.00)points respectively;the differences among the three groups were not statistically significant(P＞0.05).One week after operation,the pain was significantly relieved in all the patients of three groups;the mean VAS scores in R+P group,P group and M+P group were(4.10±0.85)points,(3.17±0.93)points and(2.44±1.23)points respectively,and the reduction in VAS score was most pronounced in M+P group(P＜0.05).Six months after operation;the mean VAS scores in R+P group,P group and M+P group were(1.87±0.84)points,(4.60±1.09)points and(1.48±0.71)points respectively;and the reduction in VAS score was most pronounced in the M+P group(P＜0.05).The used amount of bone cement in M+P group,R+P group and P group was(7.54±1.44)mL,(5.48±1.12)mL and(4.59±1.56)mL respectively,the difference among the three groups was statistically significant(P＜0.05).The vascular leakage rate(34.8％)and non-vascular leakage rate(52.2％)in P group were remarkably higher than those in R+P group and in M+P group(P＜0.05).No statistically significant difference in the rate of cement leakage existed between R+P group and M+P group(P＞0.05).Conclusion For the treatment of vertebral metastases,MW A plus PVP is superior to RFA plus PVP in pain relief rate.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.