PROPOSE: To investigate the molecular mechanisms underlying the protective effects of ischemic preconditioning (IPC) in patients undergoing total knee arthroplasty. METHODS: GSE21164 was extracted from an online database, followed by an investigation of differentially expressed genes (DEGs) between IPC treatment samples at 2 time points (T0T and T1T). Function and pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed to identify hub genes according to 5 different algorithms, followed by enrichment analysis. In addition, long noncoding RNAs (lncRNAs) were identified between the T0T and T1T samples. Furthermore, a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA (mRNA), lncRNA-microRNA (miRNA), and mRNA-miRNA relationships revealed in this study. Finally, a drug-gene network was investigated. Statistical analyses were performed using GraphPad Prism 8.0. Differences between groups were determined using an unpaired t-test. p < 0.05 was considered significant. RESULTS: A total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respective control groups, followed by 100 DEGs between T0T and T1T. Based on these 100 DEGs, protein-protein interaction network analysis revealed 9 hub genes, mainly with mitochondria-related functions and the carbon metabolism pathway. Six differentially expressed lncRNAs were investigated between T0T and T1T. A competing endogenous RNA network was constructed using 259 lncRNA-miRNA-mRNA interactions, including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold. Finally, 13 chemical drugs associated with the hub genes were explored. CONCLUSION Iron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis. Moreover, IPC may induce a protective response after total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway, which should be further validated in the near future.
Humans ; Arthroplasty, Replacement, Knee ; Ischemic Preconditioning ; RNA, Long Noncoding/genetics* ; Protein Interaction Maps ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Gene Regulatory Networks

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer. Computational methods have been widely explored and have become increasingly accurate in recent years. However, the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients. We present a novel disentangled synthesis transfer network (DiSyn) for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients. DiSyn uses a domain separation network (DSN) to disentangle drug response related features, employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement. DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets, The Cancer Genome Atlas (TCGA), Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2 (I-SPY2) and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia (NIBR PDXE), achieving competitive performance with the state-of-the-art methods on cancer patients and mice. Furthermore, the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P＜0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.01),and promoted the expression of p-SHP-2 protein(P＜0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P＜0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P＜0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P＜0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P＜0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective To analyze the infection status of Mycoplasma pneumoniae(MP)in the First Affilia-ted Hospital of Shandong First Medical University(the hospital)from 2019 to 2023 and explore the related influencing factors.Methods Basic admission information,test results,and related diagnostic results of 16 465 MP positive patients admitted to the hospital were collected,and the distribution characteristics of the number and disease types of MP positive patients in the hospital were analyzed.Results The positive rate of MP from high to low in the 5 years was in the years of 2021,2019,2020,2022,2023(P＜0.05).The proportion of MP positive cases in outpatient department from high to low was in the years of 2023,2021,2022,2019 and 2020(P＜0.05).Incidence was higher in spring and winter.In 5 years,the positivity rate of MP in respiratory tract infection patients was slightly higher in males than in females,the proportions of males in 2020 and 2022 were higher than those in 2019 and 2021(P＜0.05),and the proportions of males in 2019,2020,and 2022 were higher than that in 2023(P＜0.05).The age groups of MP infected patients were mainly concentrated in ado-lescents and infants under 14 years old.The positive results of patients in the 5 years were mainly distributed in titers of 1∶40,1∶80,and＞1∶160.There was no statistically significant difference in the proportion of positive results with MP total antibody≥1∶160 detected(P＞0.05).The top 5 clinical diagnoses of MP in-fected patients in thed hospital were fever,acute bronchitis,bronchopneumonia,chronic bronchitis,and pneu-monia,and the difference in the proportion of diagnostic results was statistically significant(P＜0.05).Conclu-sion This study clarifies the infection status of MP in the hospital from 2019 to 2023,and analyzes the impact of factors such as season,gender,and age on MP infection,which is of great significance for the prevention and control of respiratory infectious diseases in the hospital.

Objective To explore the feasibility and rationality of advanced integrated two-stage laparoscopic simulation training course in standardized training of surgical residents.Methods From December 2019 to December 2021,the advanced integrated two-stage laparoscopic simulation training course was carried out among 2019-2020 surgical residents who received standardized training in our hospital.The course was divided into two stages.In the first stage,BEST(best essential surgical technology training)course,adopted Darwin? endoscopic training system,Tianyan? endoscopic training system,Microport? 3D laparoscopic training system and simple simulative models were used.The second stage,BEST PLUS course,same platform as that in BEST course and in vitro animal models were used.The questionnaire survey method(before and after class questionnaire)was adopted to evaluate the curriculum setting,such as curriculum form,simulators,teaching method,time arrangement,curriculum difficulty,training effect,curriculum satisfaction and so on.Results A total of 37 surgical residents completed the two-stage course training and the questionnaire survey.The overall satisfaction rate with the curriculum setting was 100%.There were 32 residents(86.5%)thought that first stage training course could significantly improve their clinical skills,35 residents(94.6%)thought that second stage training course could significantly improve their clinical skills,and 36 resident(97.3%)thought that the first stage curriculum could significantly help them improve performance in the second stage curriculum.Conclusions The trainees had a high degree of recognition and satisfaction for the advanced integrated two-stage laparoscopic simulation training course.The overall design of course was reasonable and feasible,and was attractive to trainees.

Objective To explore the efficacy of thoracic endovascular aortic repair(TEVAR)for the treatment of Stanford type B aortic dissection at different intervention timing.Methods The clinical data of 126 patients with Stanford B type aortic dissection,who were admitted to authors'hospital between January 2018 and April 2023,were retrospectively analyzed.Based on the time interval from the onset of disease to receiving surgery,the patients were divided into group A(＜24 h),group B(2-7 d)and group C(8-14 d).The incidences of perioperative adverse events,including endoleak,cerebral infarction,death,aortic rupture and total complications,were compared between each other among the three groups,and survival analysis was performed according to the follow-up findings.Results A total of 126 patients with Stanford type B aortic dissection were included in this study,including 50 patients of group A,43 patients of group B,and 33 patients of group C.No statistically significant differences in the general clinical data existed between each other among the three groups(P＞0.05).The differences in the incidences of perioperative acute cerebral infarction,endoleak,infection and death between each other among the three groups were not statistically significant(P＞0.05).The difference in the overall complication rate between each other among the three groups was statistically significant(P＜0.05).Log-rank testing was used to compare the survival curves of the three groups,which showed that the cumulative 5-year recurrence rate and survival rate in group A were lower than those in group B and in group C,and the differences were statistically significant(P＜0.05).Conclusion The results of this study indicate that the patients may have high incidence of adverse events and poor short-to-middle-term curative efficacy when TEVAR is performed within 24 hours after the onset of symptoms,while the patients may have better perioperative and short-to-middle-term curative efficacy if TEVAR is carried out in 2-14 days after the onset of symptoms(J Intervent Radiol,2024,33:523-528)

Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.

Objective To investigate the targeting of transforming growth factor β1(TGF-β1)expression by Ran-binding protein 9(RANBP9)and its effect on colorectal cancer Colo320 cell apoptosis.Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database.The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments.Colo320 cells were transfected with pcDNA3.1-GFP-RANBP9 and control pcDNA3.1-GFP-RANBP9-NC plasmids,respectively,and normal control cells were established without transfection.The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry,the mitochondrial membrane potential was detected by JC-1 staining,and RANBP9 and TGF-β1 protein expression were detected by Western blot.Results RANBP9 expression was significantly reduced in colon cancer tissues.Compared with patients with low RANBP9 expression,patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue.Compared with patients with high TGF-β1 expression,patients with low TGF-β1 expression had a significantly higher survival curve(P＜0.05).RANBP9 targeted the expression of TGF-β1 in colon cancer.Compared with the normal group,cell growth,mitochondrial membrane potential,and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group(P＜0.05).Conclusions RANBP9 can target the expression of TGF-β1,promote the growth of Colo320 colon cancer cells,decrease the mitochondrial membrane potential,and induce apoptosis.

Objective To investigate TXNIP and KLF9 expressions in the tissues of colorectal cancer(CRC)and their impact on clini-cal characteristics and prognosis.Methods This study included 90 CRC patients who were admitted to our hospital between January 2017 and December 2020.The cancer tissue and paired adjacent tissues removed surgically were collected.We performed detection and analysis of TXNIP and KLF9 protein expression levels in cancer and adjacent tissues and their correlation with clinical characteristics and overall survival rate of patients.Results GEPIA database analysis showed that TXNIP and KLF9 mRNA expression levels in READ tissues were significantly lower than those in normal tissues(P＜0.05).The positive expression rates of TXNIP and KLF9 in CRC tissues were 32.22％and 37.78％,respectively,which were lower than those in adjacent tissues(73.33％and 76.67％,respectively;P＜0.05).TXNIP and KLF9 expressions were positively correlated(r=0.519,P＜0.05),and GEPIA database retrieval showed a positive correlation between TXNIP and KLF9 expressions(P＜0.05).TXNIP and KLF9 expressions in patients with clinical stage Ⅲ and lymph node metas-tasis were lower than those in patients with stage Ⅰ/Ⅱ and non-lymph node metastasis(P＜0.05).The overall survival rate of patients with TXNIP and KLF9 expressions was higher than that of patients without TXNIP and KLF9 expressions.Negative expression of TXNIP and KLF9 in TNM stage Ⅲ was a prognostic risk factor(P＜0.05).Conclusion TXNIP and KLF9 expression levels are low in CRC tissues and associated with TNM stage,lymph node metastasis,and poor survival.