Objective : To explore the mechanism of isorhamnetin (Iso) in the treatment of oral squamous cell carcinoma (OSCC) using network pharmacology and molecular docking methods and to verify it in vitro. Methods : The key targets were obtained by constructing the PPI protein interaction network based on the common intersection targets of Iso-OSCC. At the same time, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the related signaling pathways of the intersection targets. Iso and core targets were also analyzed through molecular docking and visualization. Colony formation assay and Transwell assay were used to identify the effect of Iso on the proliferation and invasion of Cal-27 cells. Western blot was used to analyze the regulatory effects of different concentrations of Iso on estrogen receptor-1 (ESR1), phosphoinositide-3-kinase regulatory subunit-1 (PIK3R1), Src tyrosine kinase (SRC), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins. Results: A total of 269 potential intersection targets of Iso-regulated OSCC were obtained. According to the degree obtained by topological analysis, PIK3R1, AKT1, SRC, ESR1, and other core targets were screened out. KEGG analysis showed that 165 signaling pathways were enriched in the intersection targets of Iso-OSCC, among which the PI3K/AKT signaling pathway played an important role in the treatment of OSCC with Iso. Molecular docking results showed that the absolute value of binding energy between target proteins PIK3R1, AKT1, SRC, ESR1, and Iso was high. After Cal-27 cells were treated with Iso, the number of cell colony formations, the number of transmembrane cells, and the expression of PIK3R1, ESR1, SRC, p-PI3K, and p-AKT were negatively correlated with the increase in Iso concentration (P < 0.05). Conclusion Iso can inhibit PI3K/AKT signal transduction and influence the expression of PIK3R1, AKT1, SRC, and ESR1 proteins, thereby inhibiting the occurrence and development of OSCC.

Objective:To construct a predictive model for the risk of major adverse cardiovascular events(MACE) after surgery in patients with symptomatic arteriosclerosis obliterans(ASO) .Methods:From Jan 2018 to Dec 2021, 957 patients with symptomatic ASO admitted to Nanjing Drum Tower Hospital were selected and divided into MACE and non-MACE groups according to whether they had a post-op MACE. A risk prediction model was constructed based on a stepwise regression method with multi-factor COX regression analysis. The model was evaluated using the receiver operating characteristic curve (ROC), the calibration curve to assess the model fit, and the Bootstrap method for internal validation.Results:MACE occurred in 143 patients (14.94%). After COX regression analysis, BMI, creatinine clearance, fibrinogen, rivaroxaban and previous history of surgery were enrolled into model constructing. The ROC curve assessed the model with a C-statistic of 0.690 (95% CI: 0.644-0.736), sensitivity and specificity of 49.2% and 80.7% respectively, a Jorden index of 0.299 and an optimal cut-off value of 0.086. Calibration curves showing agreement between predicted and actual observed values. Internally validated C-statistic of 0.689 (95% CI: 0.672-0.700). The population was divided into high and low risk groups based on the best cut-off value and analysed for survival. The difference between the two groups was statistically different. Conclusion:The risk prediction model for the occurrence of MACE based on clinical parameters is simple and convenient, with good predictability and good discriminatory ability, and can provide reference for the assessment and treatment of MACE in ASO patients.

Patients with anaplastic lymphoma kinase(ALK)fusion lung adenocarcinoma may develop drug resistance after treatment with ALK-tyrosine kinase inhibitor(ALK-TKI),and the mechanisms of this resistance are not yet fully defined.The Affiliated Hospital of Zunyi Medical University admitted a patient who was resistant to ALK fusion after ALK-TKI treatment,leading to disease progression and subsequent biopsy indicating a transformation to small cell lung cancer in September 2021.The patient,a 54-year-old female,initially presented with symptoms of cough,sputum production,and chest pain for 4 months.Chest CT showed a neoplastic lesion in the posterior segment of the right upper lobe to right lower lobe with obstructive pneumonia,metastasis in the right lower lobe,increased and enlarged mediastinal and right hilar lymph nodes,and thickening of the right hilar soft tissue.Bronchoscopy and pathological biopsy confirmed the diagnosis of lung adenocarcinoma.The results of next-generation sequencing indicated that echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)fusion is associated with tumor protein 53(TP53)and retinoblastoma 1(RB1)gene mutations.The patient received second-generation ALK-TKI aletinib,achieving a progression-free survival of 11 months before disease progression suggested aletinib resistance.Subsequently,the third-generation ALK-TKI lorlatinib administered for one month without efficacy,resulting in rapid systemic disease progression.The neuron specific enolase(NSE)was significantly increased,and the patient developed new pleural,pericardial,intracranial,liver,and multiple bone metastases occurred in a short period.A second biopsy indicated small cell lung cancer.Modification of treatment regimen to chemotherapy combined with immunotherapy proved effective.The mechanisms of drug resistance of ALK-TKI treatment for advanced non-small cell lung cancer with ALK fusion are complex,and small cell transformation of pathological type is one such mechanism,although rare.Concurrent TP53 and RB1 gene mutations may be characteristic of this transformation.Elevated NSE can serve as a predictive serum marker for adenocarcinoma transforming to small cell carcinoma.Timely re-biopsy and selection of subsequent treatments based on different resistance mechanisms are crucial for comprehensive disease management.

Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.

Objective:To apply the best evidence for the prevention of radial artery occlusion after transradial coronary angiography or intervention to clinical practice and evaluate its effect.Methods:This was a quasi-experimental study. Based on the evidence continuous quality improvement model, evidence-based practice method was used to obtain the best evidence, formulated review indicators, analyzed the obstacles in the practice process and took action strategies. The 88 patients who underwent transradial coronary angiography or intervention in the Cardiology Department of Qilu Hospital of Shandong University (Qingdao) from June 1 to 30, 2020 were selected as the baseline review group by convenience sampling. The 94 patients who underwent this treatment from September 1 to 30, 2020 were selected as the evidence application group. The baseline review group used the original perioperative management plan, and the evidence application group used the perioperative management plan based on the best evidence. The implementation rate of each review indicator, the incidence of radial artery occlusion, the degree of compression pain, and the comfort level of patients were compared between the two groups.Results:The implementation rates of review indicators 1, 2, 3, 5, 6, 7, 8 in the evidence application group were 100.0% (94/94), 100.0% (94/94), 11.7(11/94), 88.3% (83/94), 100.0% (94/94), 100.0%(94/94), 85.1%(80/94), respectively, which were higher than those in the baseline review group(all 0), except for the review indicator 4, the differences were statistically significant ( χ2 values were 9.00-178.02, all P<0.05). The incidence of radial artery occlusion and the incidence of pain Numerical Rating Scale>3 points in the evidence application group were 2.1% (2/94) and 3.2% (3/94), respectively, which were lower than 14.8% (13/88) and 23.9% (21/88) in the baseline review group; the comfort level of patients in the evidence application group was 96.8% (91/94), which was higher than 63.6% (56/88) in the baseline review group. The differences were statistically significant ( χ2 = 8.01, 15.21, 30.10, all P<0.05). Conclusions:The best evidence for the prevention of radial artery occlusion after transradial coronary angiography or intervention can be applied to clinical practice, which can standardize the behavior of medical staff, reduce the incidence of postoperative radial artery occlusion, reduce the degree of compression pain, and improve the comfort of patients.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

Objective:To construct a computed tomography (CT)-based three-dimensional digital model of small bowel, and investigate its application value for predication of small bowel length before bariatric surgery.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 patients with obesity who were admitted to the Daping Hospital of Army Medical University from December 2018 to January 2019 were collected. There were 2 males and 1 female, aged from from 24 to 44 years, with a median age of 25 years. Patients underwent abdominal enhanced CT examination before operation, and the three-dimensional digital models of small bowel for each patient were constructed respectively. Of the 3 patients, 2 underwent sleeve gastrectomy and 1 underwent Roux-en-Y gastric bypass. The 3 patients were numbered as No.1, No.2, and No.3 according to the operation time. Observation indicators: (1) construction of three-dimensional digital model of small bowel and preoperative prediction of small bowel length; (2) intraoperative measurement of small bowel length and the relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length. Count data were represented as absolute numbers or percentages.Results:(1) Construction of three-dimensional digital model of small bowel and preoperative prediction of small bowel length: the three-dimensional digital models of small bowel for each patient were constructed respectively before operation. The volume of small bowel, area of each cross-section for the 10 cross-sections of small bowel, average area of cross-section of small bowel, preoperative prediction of small bowel length in the three-dimensional digital model of small bowel of No.1 patient were 1 312 985 mm 3, 174 mm 2, 154 mm 2, 143 mm 2, 172 mm 2, 345 mm 2, 213 mm 2, 357 mm 2, 173 mm 2, 382 mm 2, 154 mm 2, 227 mm 2, 578 cm. The above indicators of No.2 patient were 1 817 224 mm 3, 274 mm 2, 196 mm 2, 487 mm 2, 413 mm 2, 520 mm 2, 254 mm 2, 231 mm 2, 170 mm 2, 212 mm 2, 168 mm 2, 293 mm 2, 620 cm. The above indicators of No.3 patient were 2 183 019 mm 3, 320 mm 2, 408 mm 2, 281 mm 2, 222 mm 2, 194 mm 2, 219 mm 2, 188 mm 2, 419 mm 2, 326 mm 2, 235 mm 2, 281 mm 2, 777 cm. (2) Intraoperative measurement of small bowel length and the relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length: the length of small bowel measured intraoperatively for No.1, No.2, and No.3 patients were 570 cm, 600 cm, and 780 cm, respectively. The relative error between preoperative prediction of small bowel length and intraoperative measurement of small bowel length of No.1, No.2, and No.3 patients were 1.40%、3.33%、0.38%, respectively. Conclusion:Three-dimensional digital model of the small bowel can predict the small bowel length before bariatric surgery.

Objective:To explore the role and mechanism of the B7-H1 expressed by auto-keratinocytes in the intermingled skin grafting model in vitro(MELC). Methods:The intermingled skin grafting model(MELC) was established in vitro. Flow cytometry was performed to detect the expressions of B7-H1 in keratinocytes. The expressions of PD-1 in lymphocytes were measured at the same time. The levels of IL-10,Foxp3 and GATA-3 mRNA in lymphocytes were detected by Real-time quantitative PCR. Results: Through flow eytometry,in the MELC with auto-keratinocytes,the expression of B7-H1 in auto-keratinocytes and the PD-1 in lymphocytes were rising trend and the rising rate was in time-dependent manners(P<0. 01). RT-PCR assay indicated that the relative levels of IL-10, Foxp3,GATA-3mRNA expression were significant raised and the rising rate was in time-dependent manners (P<0. 01). Conclusion:In the intermingled skin grafting model,the auto-keratinocytes could express B7-H1 to enhance the expression of PD-1 in T cells. When B7-H1 combined with PD-1,the Th2 cells and Foxp3+Tregs were induced and suppressed the immune response in the intermingled skin grafting model.

Objective To evaluate diagnostic value and analyze the complications of the lung nodules by 64 slice CT guided percutaneous thoracic biopsy(PTB)with coaxial technique.Methods The clinical data of 63 patients with lung placeholder in coaxial line casing biopsy under CT guidance were retrospectively analyzed.After CT positioning,16G coaxial trocar rapidly passed through the pleura,the tip to the edge of the tumor or pathological lesions,pulled out the needle core,the coaxial sleeve in 18G semi automatic biopsy needle,the materials were multi-angle cuted and sent to the pathology examination,the positive rate and the incidence of complications were analyzed.Results In 63 cases of lesions under CT guidance,the success rate of drawing materials was 100.0%,the pathological diagnosis rate was 88.9%.Intraoperative and postoperative complications occurred in 18 cases,the incidence rate was 28.6%,among them 9 cases of pneumothorax(14.3%),pulmonary hemorrhage in 8 cases(12.7%),hemoptysis in 1 case(1.6%),no severe adverse reaction was observed.Conclusion Multi slice CT guided percutaneous coaxial biopsy has the advantages of simple operation,high diagnosis rate,less complications,low risk,it can be promoted in hospitals.