Chemical modifications of nitrogenous bases or ribosemoieties are common in RNA molecules and these RNA modifications regu-late tumor progression by modulating gene expression in malignancies.Therefore,delving into the role of RNA modifications in tumor pro-gression is essential for understanding tumor progression mechanisms and developing intervention strategies.Mitochondria are crucial for maintaining the energy state of malignant tumor cells.Recent studies have indicated that RNA modifications and tumor mitochondria are closely connected,implying that mitochondrial function within tumors can be disrupted due to RNA modifications.This article focuses on the role and underlying mechanisms of RNA modifications in tumor mitochondria,offering crucial insights for a deeper understanding of the reg-ulatory mechanisms of tumor metabolism and the development of new innovative therapeutic strategies.

Objective:To explore the feasibility of the AI intelligent reconstruction model based on knee joint magnetic resonance data developed by Nuctech Company Limited for evaluating knee cartilage injury.Methods:Thirty-three patients (a total of forty-one knees) who were hospitalized with severe knee osteoarthritis in Beijing Tsinghua Changgung Hospital from May 2021 to April 2022 were selected. All of them were planned to be performed total knee arthroplasty (TKA) for the treatment of knee osteoarthritis. Fifteen males with an average age of 71±5 years old and twenty six females with an average age of 71±9 years old were included in this study. There were 19 cases of left knee and 22 cases of right knee. Thin layer MRI examination on the patients' knee joints was performed before the surgery, and artificial intelligence model based on the thin layer MRI data of the knee joint was reconstructed. The cartilage part of the model was selected and corrected by Principal Component Analysis (PCA) in order to realize model straightening. The tibial plateau cartilage of knee joint which intercepted during operation was classified according to the International Cartilage Repair Society (ICRS). Finally the results were compared with the ICRS classification results of knee artificial intelligence reconstruction model and artificial recognition of knee joint MRI images.Results:Compared with the grade of cartilage injury intercepted during our operation which was according to the ICRS classification, the sensitivity of artificial intelligence reconstruction model for the diagnosis of cartilage injury with ICRS classification grade four was 93.1%. The specificity of artificial intelligence reconstruction model was 91.4%. The positive predictive value (PPV) of artificial intelligence reconstruction model was 92.2%. And the negative predictive value (NPV) of artificial intelligence reconstruction model was 80.3%. The area under ROC curve (AUC) was 0.92. The ICRS classification consistency between artificial intelligence model and physical inspection results was good with kappa value 0.81 ( P<0.001) . In the aspect of artificial recognition of cartilage injury grading in MRI images, the sensitivity of artificial recognition was 92.10% compared with the manual identification of cartilage injury classification in MRI images. The specificity of artificial recognition was 91.60%. The positive predictive value (PPV) of artificial recognition was 97.20% and the negative predictive value (NPV) of artificial recognition was 78.8%. The kappa value of the cartilage injury classification in MRI images consistency between artificial recognition and manual identification was 0.79 ( P<0.001). Conclusion:Based on the evaluation of cartilage injury by AI reconstruction model of knee joint, the sensitivity and specificity of the diagnosis of ICRS grade IV cartilage injury can be acceptable, but still needs to be improved.

Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
Animals ; Mice ; Ferroptosis ; Network Pharmacology ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; Influenza A virus ; Iron ; Hypoxia

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Objective:To compare 5-year overall survival (OS) and disease free survival (DFS) between preoperative three dimensional conformal radiotherapy (3DCRT) and volumetric medulated arc therapy (VMAT) concurrently combined with chemotherapy for locally advanced rectum cancer (LARC), and analyze the value of induction and/or consolidation chemotherapy in these circumstances.Methods:334 patients with LARC treated with preoperative 3DCRT (172 cases) and VMAT (162 cases) concurrently combined with chemotherapy, main protocol XELOX (capecitabine plus oxaplatin), and subsequent surgery in Sun Yat-sen University from May 2007 to April 2013 were retrospectively analyzed. The radiation prescription dose for VMAT group was 50 Gy 25 fractions for planning target volume1(PTV 1), and 46 Gy 25 fractions for PTV 2. The radiation prescription dose for 3DCRT group was 46 Gy 23 fractions for PTV 2. One hundred and eighty-five cases of all received preoperative concurrent chemoradiotherapy (namely, CCRT group), 149 cases received preoperative concurrent chemoradiotherapy plus median 2 courses (1-7 courses) induction and/or consolidation chemotherapy (namely, CCRT±induction chemotherapy±consolidation chemotherapy group), whose main chemotherapy protocol was XELOX. Difference of 5-year OS and DFS between 3DCRT and VMAT group was compared. The rate differences of acute toxicity during chemoradiotherapy, postoperative complications, ypCR, and survival between CCRT group and CCRT±induction chemotherapy±consolidation chemotherapy group were analyzed. Results:After a median follow-up of 62.3 months (2.4-119months) for the 334 patients, no any significant difference for 5-year OS (79.0% vs. 83.2%, P=0.442) and 5-year DFS (77.0% vs. 82.1%, P=0.231) between 3DCRT and VMAT group was observed. There was no any significant difference for the Grade 3 hematological toxicity (7.0% vs. 12.1%, P=0.114) and non-hematological toxicity (14.1% vs. 16.8%, P=0.491) during chemoradiotherapy, postoperative complications (17.3% vs. 17.4%, P=0.971), ypCR rate (25.4% vs. 30.2%, P=0.329), 5-year OS (80.5% vs. 82.0%, P=0.714) and 5-year DFS (78.8% vs. 81%, P=0.479) between CCRT group and CCRT±induction chemotherapy±consolidation chemotherapy group. Conclusions:Compared with 3DCRT, the physics advantage of VMAT technique does not significantly convert into clinical benefits and improve 5-year OS and DFS, even further boosting radiation dose to the gross tumor volume. It is safe for median 2 courses of induction and/or consolidation chemotherapy before and or after preoperative concurrent chemoradiotherapy in the treatment of LARC, though it does not significantly improve ypCR rate and survival.

Objective:To establish a nomogram model for predicting the risk of coronary artery disease in elderly patients with acute myocardial infarction (AMI).Methods:The clinical data of elderly patients with AMI who underwent coronary angiography in the department of cardiology of Cangzhou Central Hospital from July 2015 to March 2020 were analyzed, including age, gender, smoking history, underlying diseases, family history, blood pressure, left ventricular ejection fraction (LVEF), and several biochemical indicators at admission, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein [Lp(a)], apolipoproteins (ApoA, ApoB), ApoA/B ratio, total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil), fasting blood glucose (FBG) and uric acid (UA). Patients were divided into model group (2 484 cases) and validation group (683 cases) according to the ratio of 8∶2. According to Gensini score, the model group and validation group were divided into mild lesion group (0-20 points) and severe lesion group (≥81 points). The differences of each index between different coronary lesion degree groups were compared. Lasso regression and Logistic regression were used to analyze the risk factors of aggravating coronary lesion risk in elderly patients with AMI, and then the nomogram prediction model was established for evaluation and external validation.Results:① In the model group, there were significant differences in the family history of coronary heart disease, FBG and HDL-C between the mild lesion group (411 cases) and the severe lesion group (417 cases) [family history of coronary heart disease: 3.6% vs. 7.7%, FBG (mmol/L): 5.88±1.74 vs. 6.43±2.06, HDL-C (mmol/L): 1.48±0.69 vs. 1.28±0.28, all P < 0.05]. In the validation group, there were significant differences between the mild lesion group (153 cases) and the severe lesion group [132 cases; FBG (mmol/L): 5.58±0.88 vs. 6.85±0.79, HDL-C (mmol/L): 1.59±0.32 vs. 1.16±0.21, both P < 0.05]. ② Lasso regression analysis showed that family history of coronary heart disease, FBG, and HDL-C were risk factors of coronary artery disease in elderly patients with AMI, with coefficients 0.118, 0.767, and -0.558, respectively. Logistic regression analysis showed that FBG [odds ratio ( OR) = 1.479, 95% confidence interval (95% CI) was 1.051-2.082, P = 0.025] and HDL-C ( OR = 0.386, 95% CI was 0.270-0.553, P < 0.001] were independent risk factors of coronary artery disease in elderly patients with AMI. ③ According to the rank score of FBG and HDL-C, the nomogram prediction risk model of aggravating coronary artery disease degree was established for each patient. It was concluded that the risk of coronary artery disease in elderly people with higher FBG level and (or) lower HDL-C level was significantly increased. ④ The nomogram model constructed with the model group data predicted the risk concordance index (C-index) was 0.689, and the C-index of the external validation group was 0.709. Conclusions:FBG and HDL-C are independent risk factors for aggravating coronary artery disease in elderly patients with AMI. The nomogram model of aggravating coronary artery disease in elderly patients with AMI has good predictive ability, which can provide more intuitive research methods and clinical value for preventing the aggravation of coronary artery disease in elderly patients.

BACKGROUND: To compare the clinical efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer through evidence based medicine analysis. METHODS: A systematic search was performed in the PubMed, EMBASE, CNKI and Wan Fang databases to find studies published before June 2020. Two authors independently extracted the data and assessed the eligibility. All of the statistical analyses were performed using Stata 13.0. Subgroup analysis were performed according to the score matching study and operation type (lobectomy, segmentectomy and thoracoscopic assisted surgery). RESULTS: Finally, 14 articles were included, including 15,841 cases in SBRT group and 17,708 cases in operation group. 10 articles used propensity score matching methods for survival analysis. Thirteen were retrospective cohort studies and one was randomized controlled trial. The results of meta-analysis showed that the overall survival rate of the surgery group and the SBRT group was statistically significant. The overall survival rate of the SBRT group (HR=1.51, 95%CI: 1.31-1.74) was inferior to that of the surgery group. In the subgroup analysis of the surgical type, there was no statistical difference between the SBRT group and each surgical type. The difference of overall survival rate between SBRT group and surgery group was statistically significant (HR=1.66, 95%CI: 1.45-1.90) in studies of propensity score matching. There was no statistically significant difference in cancer-specific survival between the surgery and SBRT groups (HR=1.12, 95%CI: 0.83-1.52). CONCLUSIONS The overall survival rate of surgical treatment is better than that of SBRT, but it has no obvious advantages in cancer specific survival rate.

Objective:To analyze the incidence of recent complications in patients with osteoarthritis of the knee (OA) after medial opening wedge high tibial osteotomy(MOWHTO) and its influence on clinical effect.Methods:The clinical data of 131 patients with knee OA who received MOWHTO at Department of Sports Medicine and Arthroscopy,Tianjin Hospital from April 2017 to September 2018 were analyzed retrospectively. There were 75 males and 56 females, aged (62.8±5.1) years (range:48 to 70 years). Complications and clinical outcomes of patients were recorded and the proximal medial angle of tibia (MPTA), the International Knee Documentation Committee Subjective Knee Form (IKDC), the Western Ontario and McMaster Universities(WOMAC) Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome score(KOOS) were collected before and 1 year after operation and compared between complication group and non-complication group. Data were analyzed by paired-samples t test, independent samples t test and χ 2 test. Results:The follow-up time was (18.5±3.4) months (range:13 to 22 months). Complications occurred in 22 patients(16.8%), including 8 cases(6.1%) of hematoma, 5 cases(3.8%) of neurosensory abnormality, 4 cases(3.1%) of intramuscular venous thrombosis, 2 cases(1.5%) of deep venous thrombosis, 3 cases(2.3%) of loss of correction angle, 3 cases(2.3%) of superficial infection, 2 cases(1.5%) of deep infection, 2 cases(1.5%) of delayed union of fracture, 1 case(0.8%) of postoperative stiffness, 1 case (0.8%) of hinge point cortex fracture. There were no significant difference in MPTA ((86.5±2.0)° vs. (86.7±2.1)°, t=-0.41, P=0.68) , IKDC ((86.4±4.8) vs.(85.5±6.9), t=0.74, P=0.50) , WOMAC ((87.7±6.5) vs. (86.1±5.8), t=1.16, P=0.25). There were no significant difference in knee scores except for the KOOS pain score ((79.4±4.4) vs. (87.2±5.9), t=-5.90, P<0.01) and sports and recreation score ((83.2±3.0) vs. (88.0±4.7), t=-6.14, P<0.01) . Conclusion:Short-term complications of MOWHTO can be managed appropriately through early diagnosis and individualized treatment and have no significant negative effect on knee function recovery of patients.

Objective:To analyze the incidence of recent complications in patients with osteoarthritis of the knee (OA) after medial opening wedge high tibial osteotomy(MOWHTO) and its influence on clinical effect.Methods:The clinical data of 131 patients with knee OA who received MOWHTO at Department of Sports Medicine and Arthroscopy,Tianjin Hospital from April 2017 to September 2018 were analyzed retrospectively. There were 75 males and 56 females, aged (62.8±5.1) years (range:48 to 70 years). Complications and clinical outcomes of patients were recorded and the proximal medial angle of tibia (MPTA), the International Knee Documentation Committee Subjective Knee Form (IKDC), the Western Ontario and McMaster Universities(WOMAC) Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome score(KOOS) were collected before and 1 year after operation and compared between complication group and non-complication group. Data were analyzed by paired-samples t test, independent samples t test and χ 2 test. Results:The follow-up time was (18.5±3.4) months (range:13 to 22 months). Complications occurred in 22 patients(16.8%), including 8 cases(6.1%) of hematoma, 5 cases(3.8%) of neurosensory abnormality, 4 cases(3.1%) of intramuscular venous thrombosis, 2 cases(1.5%) of deep venous thrombosis, 3 cases(2.3%) of loss of correction angle, 3 cases(2.3%) of superficial infection, 2 cases(1.5%) of deep infection, 2 cases(1.5%) of delayed union of fracture, 1 case(0.8%) of postoperative stiffness, 1 case (0.8%) of hinge point cortex fracture. There were no significant difference in MPTA ((86.5±2.0)° vs. (86.7±2.1)°, t=-0.41, P=0.68) , IKDC ((86.4±4.8) vs.(85.5±6.9), t=0.74, P=0.50) , WOMAC ((87.7±6.5) vs. (86.1±5.8), t=1.16, P=0.25). There were no significant difference in knee scores except for the KOOS pain score ((79.4±4.4) vs. (87.2±5.9), t=-5.90, P<0.01) and sports and recreation score ((83.2±3.0) vs. (88.0±4.7), t=-6.14, P<0.01) . Conclusion:Short-term complications of MOWHTO can be managed appropriately through early diagnosis and individualized treatment and have no significant negative effect on knee function recovery of patients.

Objective To investigate the feasibility of non-operative management (NOM) by comparing the therapeutic effects between NOM and total mesorectal excision (TME) for rectal cancer patients with clinical complete response (cCR) after neo-adjuvant chemoradiotherapy.Methods A total of 135 patients with stage Ⅱ/Ⅲ rectal cancer who obtained cCR after neo-adjuvant chemoradiotherapy in Sun Yat-sen University Cancer Center from 2006 to 2016 were recruited and assigned into the NOM (n =43) and standard operative management (SOM) groups (n=92).The local recurrence rate,accumulative local control (LC) rate after salvage therapy,disease-free survival (DFS),overall survival (OS) and sphincter preservation rate were statistically compared between two groups.Kaplan-Meier analysis and log-rank test were utilized to calculate the LC,OS and DFS.Chi-square test was performed to calculate the sphincter preservation rate.Results The mean follow-up duration was 39 months (range:10-127 months).Of 135 patients,the local recurrence rate and distant metastasis rate were 3.7％ and 11.1％,and the 3-year DFS and OS were 90.5％ and 97.0％.In the NOM and SOM groups,the 3-year DFS were 87％ and 93％,and the 5-year DFS were 73％ and 87％(P=0.089).The 3-year OS were 98％ and 99％,and the 5-year OS were 98％ and 97％ (P=0.578).In the NOM group,the local recurrence rate was 12％ (n =5),80％ of patients received salvage treatment and the accumulative LC rate was calculated as 98％.In the SOM group,the local recurrence rate was 0,which was significantly lower than that in the NOM group (P=0.O10).In the NOM group,the sphincter preservation rate was 93％,significantly higher compared with 70％ in the SOM group (P=0.030).Conclusions It is feasible for rectal cancer patients with cCR to receive NOM following neo-adjuvant chemoradiotherapy.Partial locally recurrent patients can be healed by timely salvage therapy,thereby averting TME and relevant complications and enhancing the quality of life of rectal cancer patients.