1.The role and mechanism of FTO in the occurrence and development of gastrointestinal malignancies and research progress in its applications
Hao CHEN ; Yuanliang LI ; Haogang ZHANG ; Pengfei QIAO
Chinese Journal of General Surgery 2024;33(10):1714-1723
Gastrointestinal malignant tumors are common worldwide,particularly gastric cancer(GC)and colorectal cancer(CRC),with complex and not fully understood molecular mechanisms behind their occurrence and progression.Treatment typically involves a comprehensive approach centered on surgery,which,despite achieving good outcomes,still faces challenges due to high recurrence rates and low survival rates impacting patient health.N6-methyladenosine(m6A)is the most abundant internal modification in mRNAs and plays a crucial role in regulating RNA post-transcriptional modifications and downstream functions.Fat mass and obesity-associated protein(FTO)was the first identified m6A demethylase capable of removing dynamic,reversible m6A modifications.During the development of gastrointestinal malignancies,FTO regulates the expression of specific genes,affecting tumor cell proliferation and metastasis;modulates the expression of tumor-related cytokines and immune-related molecules,influencing the tumor microenvironment;and plays a significant role in sensitivity and resistance to chemotherapy.FTO is upregulated in most types of GC,indicating poor prognosis.High FTO expression enhances GC cell migration and invasion,increases chemoresistance,promotes tumor stem cell proliferation and differentiation,and inhibits apoptosis,thus facilitating GC progression.In CRC,many studies show that FTO is upregulated in tissues and cells,promoting CRC progression by enhancing cell proliferation,migration,invasion,and resistance to chemotherapy.Low FTO expression can also elevate m6Am levels in CRC cell cytoplasmic mRNA,promoting tumor stem cell proliferation,differentiation,tumor formation,and increasing resistance.In contrast,high FTO expression inhibits tumor stem cell proliferation and differentiation.FTO is also upregulated in other gastrointestinal tumors like pancreatic and esophageal cancers,where high expression promotes progression and indicates poor prognosis.FTO has both promoting and inhibitory effects on liver and biliary malignancies.As research confirms FTO's widespread oncogenic role in the gastrointestinal tract,developing FTO inhibitors and related drugs offers new avenues for treating gastrointestinal malignancies.Currently identified agents like CS1,omeprazole,and mupirocin significantly inhibit CRC and GC progression by directly or indirectly suppressing FTO.Tumors can evade immune surveillance through FTO-mediated mechanisms,suggesting that blocking FTO-mediated immune escape and enhancing the antitumor effects of immune cells could provide treatment options for gastrointestinal malignancies.Targeting FTO in combination with immunotherapy to inhibit GC and CRC growth and metastasis and reduce resistance presents broad therapeutic prospects.
2.Intravoxel incoherent motion and dynamic contrast-enhanced MRI for assessing abnormalities of brucellosis spondylitis without conventional MRI changes
Haohua WANG ; Pengfei ZHAO ; Pengfei QIAO
Chinese Journal of Medical Imaging Technology 2024;40(8):1226-1230
Objective To observe the value of intravoxel incoherent motion(IVIM)and dynamic contrast-enhanced MRI(DCE-MRI)for assessing abnormalities of brucellosis spondylitis(BS)without conventional MRI changes.Methods Data of 36 brucellosis patients with definite spinal lesions displayed on conventional MRI(BS1 group),14 cases without brucellosis infection nor abnormal spinal signals on MRI(control group)and 36 brucellosis patients without definite spinal lesions on conventional MRI(BS2 group)were retrospectively analyzed.The values of IVIM parameters,including perfusion fraction(f),pure water diffusion coefficient(D)and pseudo-diffusion coefficient(D*),also of DCE-MRI parameters,including time-intensity curve(TIC)type,volume transport constant(Ktrans),the rate constant(Kep)and volume fraction of extravascular extracellular space per unit tissue volume(Ve)were compared among groups.Univariate and multivariate logistic regression were used to screen independent factors for discriminating BS1 and BS2.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated to evaluate the efficiency of the above parameters for discriminating BS1 and BS2.Results Among IVIM parameters,compared with control group,D*values decreased but D values increased in BS1 group,while D*values increased in BS2 group(all adjusted P<0.05).Compared with BS2 group,BS1 group had higher values of f and D and lower D*(all adjusted P<0.05).In BS1 group,the TIC types were predominantly type Ⅰ(23/36,63.89%),which were wholly or predominantly type Ⅲ in BS2 group and control group,and of the former was significantly different with latter 2(both adjusted P<0.05).Compared with control group,Ktrans increased progressively in both BS1 and BS2 groups(both adjusted P<0.05).BS1 group had lower Kep and higher Ve than BS2 and control groups(all adjusted P<0.05).Among univariate logistic regression models,the model including only f had lower capability for discriminating BS1 and BS2(AUC=0.759)than those including D,Ktrans and Ve(AUC=0.951,0.833,0.894,all P<0.05).No significant different was found among multivariate logistic regression model including f and D,model including Ktrans and Ve nor model including all above parameters(all P>0.05).Conclusion Both IVIM and DCE-MRI could be used to evaluate BS abnormality without conventional MRI changes.
3.Application of comprehensive teaching based on multiple evaluation in general surgery practice teaching
Pengfei QIAO ; Haogang ZHANG ; Fujing WANG
Chinese Journal of Medical Education Research 2023;22(4):573-577
Objective:To explore the practice of comprehensive teaching based on multiple evaluation in general surgery practice teaching.Methods:A total of 83 students were selected from the General Surgery Department, The Second Affiliated Hospital of Harbin Medical University. Among them, 40 interns used traditional teaching (control group) and 43 interns used comprehensive teaching based on multiple evaluation (experimental group). After the teaching, the assessment results of the theoretical knowledge and skill operation of the two groups of interns were evaluated, and the instructor evaluated the comprehensive ability of the interns, and evaluated the teaching satisfaction and teaching feedback results. SPSS 24.0 was used for t-test and Chi-square test. Results:After the teaching, the examination scores of interns' theoretical knowledge and skill operation in the experimental group [(94.24±2.28) points and (92.33±2.58) points] were higher than those in the control group [(90.56±2.37) points and (88.75±2.41) points]. The scores of independent learning ability, independent thinking ability, logical thinking ability, group cooperation ability, and humanistic care ability of interns in the two groups after teaching were significantly higher than those before teaching, and the scores of each ability in the experimental group were higher than those in the control group ( P<0.05). The total satisfaction rate of interns in the experimental group [95.35% (41/43)] was higher than that in the control group [75.00% (30/40)], and the difference was statistically significant ( P<0.05). The experimental group in improving the participation and learning efficiency of interns in teaching activities [97.67% (42/43), 90.70% (39/43)] was significantly higher than the control group [75.00% (30/40), 70.00% (28/40)] ( P<0.05). Conclusion:The application of comprehensive teaching based on multiple evaluation in general surgery practice teaching can help improve the interns' theoretical knowledge and skill operation performance, improve their comprehensive ability and teaching satisfaction, and improve their learning enthusiasm and efficiency, which deserves promotion and application.
4.Imaging findings and related risk factors of small vessel cerebral vascular disease in patients with systemic lupus erythematosus
Yue MA ; Ning TIE ; Pengfei QIAO ; Sha NI ; Xueying MA
Chinese Journal of Rheumatology 2023;27(9):611-617
Objective:To explore the characteristics of imaging findings and related risk factors of small vessel cerebral vascular disease (CSVD) in patients with systemic lupus erythematosus (SLE) with different disease activity.Methods:One hundred and ninty four SLE patients were included. Patients were divided into three groups according to systemic lupus erythematosus disease activity index (SLEDAI): stable or mild active disease group (0~9 points) ( n=107), moderate active group (10~14 points) ( n=41), severe active group (≥ 15 points) ( n=46). Imaging findings, general clinical information laboratory tests of all patients were collected, and the imaging data were scored according to the small cerebral vessel score scale. CSVD-related risk factors of SLE patients in the three groups were analyzed by using ordered Logistic regression. Results:There were significant differences in TWMH score, TPVS score and CSVD score among the three groups ( H=6.07, 6.00, 9.63, P<0.05). Orderly logistic regression showed that age [ OR(95% CI)=1.119 (1.051, 1.891), P<0.001], HCT [ OR (95% CI)=1.531 (1.158, 2.026), P=0.003], anti-PM-Scl antibody [ OR (95% CI)=17.271 (1.442, 206.851), P=0.025] were risk factors for CSVD in the severe active disease group. RBC [ OR(95% CI)=0.011 (0.001, 0.155), P=0.001]、anti-Rib.p antibody [ OR(95% CI)=0.093 (0.018,0.047), P=0.004] were protective factors for CSVD. Conclusion:The manifestations of CSVD in SLE patients with different disease activity are different, and are affected by age, part of blood indicators and lupus antibodies.
5.Feasibility of Free-Breathing, Non-ECG-Gated, Black-Blood Cine Magnetic Resonance Images With Multitasking in Measuring Left Ventricular Function Indices
Pengfei PENG ; Xun YUE ; Lu TANG ; Xi WU ; Qiao DENG ; Tao WU ; Lei CAI ; Qi LIU ; Jian XU ; Xiaoqi HUANG ; Yucheng CHEN ; Kaiyue DIAO ; Jiayu SUN
Korean Journal of Radiology 2023;24(12):1221-1231
Objective:
To clinically validate the feasibility and accuracy of cine images acquired through the multitasking method, with no electrocardiogram gating and free-breathing, in measuring left ventricular (LV) function indices by comparing them with those acquired through the balanced steady-state free precession (bSSFP) method, with multiple breath-holds and electrocardiogram gating.
Materials and Methods:
Forty-three healthy volunteers (female:male, 30:13; mean age, 23.1 ± 2.3 years) and 36 patients requiring an assessment of LV function for various clinical indications (female:male, 22:14; 57.8 ± 11.3 years) were enrolled in this prospective study. Each participant underwent cardiac magnetic resonance imaging (MRI) using the multiple breath-hold bSSFP method and free-breathing multitasking method. LV function parameters were measured for both MRI methods. Image quality was assessed through subjective image quality scores (1 to 5) and calculation of the contrast-to-noise ratio (CNR) between the myocardium and blood pool. Differences between the two MRI methods were analyzed using the Bland–Altman plot, paired t-test, or Wilcoxon signed-rank test, as appropriate.
Results:
LV ejection fraction (LVEF) was not significantly different between the two MRI methods (P = 0.222 in healthy volunteers and P = 0.343 in patients). LV end-diastolic mass was slightly overestimated with multitasking in both healthy volunteers (multitasking vs. bSSFP, 60.5 ± 10.7 g vs. 58.0 ± 10.4 g, respectively; P < 0.001) and patients (69.4 ± 18.1 g vs. 66.8 ± 18.0 g, respectively; P = 0.003). Acceptable and comparable image quality was achieved for both MRI methods (multitasking vs. bSSFP, 4.5 ± 0.7 vs. 4.6 ± 0.6, respectively; P = 0.203). The CNR between the myocardium and blood pool showed no significant differences between the two MRI methods (18.89 ± 6.65 vs. 18.19 ± 5.83, respectively; P = 0.480).
Conclusion
Multitasking-derived cine images obtained without electrocardiogram gating and breath-holding achieved similar image quality and accurate quantification of LVEF in healthy volunteers and patients.
6.Mechanism of Ganshuang granule extract in alleviating N-acetyl-p-aminophenol-induced hepatocellular injury
Qiao WU ; Pengfei YU ; Yanzhen BI ; Baozeng WANG ; Zixuan WANG ; Zhijie LI ; Yu CHEN ; Zhongping DUAN
Journal of Clinical Hepatology 2021;37(1):120-125
ObjectiveTo investigate the ability of Ganshuang granule (a liver-protecting drug widely used in clinical practice) extract to reduce N-acetyl-p-aminophenol (APAP)-induced hepatotoxicity and possible mechanisms. MethodsA total of five cell culture groups were set up in this experiment, i.e., normal control group, APAP injury group, and three injury protection groups treated with different concentrations of Ganshuang granule extract. Then 20 mmol/L APAP was added to the cell culture medium and incubated for 24 hours to establish an in vitro model of drug-induced liver injury, and the injury protection groups were treated with different concentrations of Ganshuang granule extract (0.2, 1, and 5 μg/ml) in advance for 8 hours of incubation before APAP were added for 24 hours. Related markers were measured, including the markers for hepatocellular injury [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], the markers for mitochondrial injury [mitochondrial membrane potential, and glutamate dehydrogenase (GDH)], and antioxidant and oxidative stress markers [glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS)]. Related mechanism was discussed based on the experimental results. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsGanshuang granule extract alleviated APAP-induced hepatotoxicity, improved cell viability (P<0001), and reduced the levels of AST, ALT, and LDH in supernatant (P<0.001, P<0.001, and P<0.05). Ganshuang granule extract inhibited APAP-induced hepatocellular oxidative stress, and compared with the APAP group, the Ganshuang granule extract groups had significant reductions in the oxidative stress indicators ROS and MDA (both P<0.01). Ganshuang granule extract alleviated the loss of mitochondrial membrane potential induced by APAP (P<0.05) and reduced the content of the mitochondrial injury marker GDH in supernatant (P<0.001) in a dose-dependent manner. Ganshuang granule extract inhibited the expression of CYP2E1/1A2 (both P<0.05) and increased the expression of phase Ⅱ enzymes in hepatocytes. Ganshuang granule extract induced the expression of Nrf2 and its downstream genes NQO-1 and GCLC (all P<0.05). ConclusionGanshuang granule extract can prevent APAP-induced hepatocellular injury through two ways. The first way is that Ganshuang granule extract downregulates the expression of CYP2E1/1A2 and thus reduces the production of NAPQI, a toxic product of APAP; the second way is that Ganshuang granule extract upregulates the expression of the detoxification pathway, which can activate Nrf2 to increase the expression of antioxidant enzymes (SOD and GSH) and phase Ⅱ enzymes and thus accelerate the harmless metabolism of APAP.
7.Association between preoperative hemoglobin amount and incidence of lower limb deep vein thrombosis following lower limb fracture
Shuhao LI ; Kun ZHANG ; Zhe SONG ; Lisong HENG ; Dongxu FENG ; Wei FAN ; Xiaolong WANG ; Chen WANG ; Rui QIAO ; Jiarui YANG ; Pengfei WANG ; Yangjun ZHU
Chinese Journal of Orthopaedic Trauma 2021;23(10):864-870
Objective:To study the association between preoperative hemoglobin amount and incidence of lower limb deep vein thrombosis (DVT) in patients with lower limb fracture.Methods:A retrospective study was performed of the 2, 482 patients with lower limb fracture who had been treated at Department of Orthopaedics Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University from July 2014 to August 2019. They were 1, 174 males and 1, 308 females with an age of (60.6±19.3) years. Recorded were the patients' age, gender, injury time, hemoglobin amount, D-dimer measurement, combined medical conditions, time and results of ultrasound vein examination on both lower extremities. According to the ultrasound results, the patients were divided into a thrombosis group and a thrombosis-free group. The 2 groups were compared in hemoglobin amount. Logistic regression was used to analyze the relationship between preoperative hemoglobin amount and incidence of lower limb DVT. The patients were divided into 5 groups according to the quintile of hemoglobin amount; the incidences of thrombosis were compared between the 5 groups.Results:The total incidence of DVT in this cohort was 29.53%(733/2, 482). The hemoglobin amount in the thrombosis group was (116.57±19.24) g/L, significantly lower than that in the thrombosis-free group (124.76±19.79) g/L ( P<0.05). The preoperative hemoglobin amount was a risk factor for incidence of DVT after a lower limb fracture ( OR=0.985, 95% CI: 0.980 to 0.990, P<0.001). As the quintile level of hemoglobin increased, the incidence of DVT showed a downward trend. In comparison of the group with the highest DVT incidence (40.58%) and the group with the lowest DVT incidence (17.27%), the risk increased by 2.386 times (95% CI: 1.718 to 3.315). Conclusions:The preoperative hemoglobin amount can affect the DVT incidence after a lower limb fracture, and a low hemoglobin amount may more likely lead to lower limb DVT.
8.Effect of continuous intravenous infusion of low-dose heparin on preventing thrombosis during perioperative period of simultaneous pancreas-kidney transplantation
Meisi LI ; Jianhui DONG ; Pengfei QIAO ; Jihua WU ; Ke QIN ; Liugen LAN ; Hongliang WANG ; Zhuangjiang LI ; Haibin LI ; Zhao GAO ; Xuyong SUN
Chinese Journal of Organ Transplantation 2021;42(4):234-238
Objective:To evaluate the efficacy and safety of continuous infusion of low-dose intravenous (Ⅳ) heparin during perioperative period of simultaneous pancreas-kidney (SPK) transplantation for donation after citizen death (DCD) donor to prevent pancreatic thrombosis post-transplantation.Methods:From January 2015 to August 2019, 46 DCD donors undergoing SPK were divided into retrospective cohort groups 1 ( n=27) and 2 ( n=19). Group 1 received aspirin enteric-coated tablets only at Day 1 post-SPK. In Group 2, 5-7 days of continuous infusion of heparin 260 IU per hour at Day 1 post-SPK was followed by a daily intake of aspirin enteric-coated tablets of 100 mg. Incidence of thrombus, recovery of graft function and adverse reactions of anticoagulant therapy were observed. Results:Thrombosis occurred in (5.3%, 1/19 vs 14.8%, 4/27) in heparin and non-heparin groups. Thrombosis and graft loss were significantly lower in heparin group than those in non-heparin group ( P<0.05). Conclusions:Continuous infusion of low-dose heparin vein is effective and safe in preventing thrombosis after SPK transplantation.
9.Relationship between autophagy regulated by chromosome 19 open reading frame 5 and malignant degree of colorectal cancer and chemosensitivity of paclitaxe
Bingwen YAN ; Shenglong LI ; Chunjing WANG ; Pengfei QIAO ; Fujing WANG
Chinese Journal of Postgraduates of Medicine 2020;43(5):439-443
Objective:To observe the relationship between autophagy regulation activity of chromosome 19 open reading frame 5 (C19ORF5) and malignant degree of colorectal cancer and chemosensitivity of paclitaxel.Methods:The tumor tissues and normal adjacent tissues of 141 colorectal cancer patients from 2015 to 2017 in the Second Affiliated Hospital of Harbin Medical University were selected. The expressions of C19ORF5 protein and mRNA were detected by immunohistochemistry and timed quantitative polymerase chain reaction. The correlation between C19ORF5 protein regulating autophagy activity and malignancy of colorectal cancer was analyzed. All 141 patients received postoperative chemotherapy, among whom 91 patients received conventional chemotherapy (capecitabine combined with oxaliplatin, conventional chemotherapy group), and 50 patients received conventional chemotherapy combined with paclitaxel (paclitaxel group). Six course of treatment was treated in both groups.Results:Autophagosomes could been seen under transmission electron microscopy. C19ORF5 protein was pale yellow to tan granules, and was expressed in the cytoplasm. The C19ORF5 protein staining intensity of cancer tissue was significantly stronger than that of normal tissue, and the staining intensity of stage Ⅱ was significantly higher than that of stage Ⅳ. The high expression rate of C19ORF5 protein in patients with stage Ⅰ to Ⅱ was significantly higher than that in patients with stage Ⅲ to Ⅳ: 83.3% (25/30) vs. 17.1% (19/111), and there was statistical difference ( P<0.01). The expression of C19ORF5 mRNA in cancer tissues was significantly higher than that in normal tissues: 1.17 ± 0.45 vs. 0.82 ± 0.29, and there was statistical difference ( P<0.05). The expression level of C19ORF5 protein in cancer tissue was related to tumor stage, carcinoembryonic antigen and liver metastasis ( P<0.01 or <0.05); the expression level of C19ORF5 protein in cancer tissue was not related to lymph node metastasis ( P>0.05). Of the 91 cases in conventional chemotherapy group, chemotherapy was effective in 70 cases (76.9%) and ineffective in 21 cases (23.1%). Of 50 cases in paclitaxel group, it was effective in 42 cases (84.0%) and ineffective in 8 cases (16.0%). There was no statistical difference in effective rate between 2 groups ( P>0.05). In conventional chemotherapy group, there was no significant difference in serum C19ORF5 protein expression levels between cancer tissues before and after chemotherapy in effective patients and ineffective patients ( P>0.05); there was no significant difference in serum C19ORF5 protein expression levels between effective patients and ineffective patients after chemotherapy ( P>0.05). In paclitaxel group, the expression level of C19ORF5 protein in cancer tissues before chemotherapy was significantly higher than that in serum C19ORF5 protein after chemotherapy: 0.9 ± 0.3 vs. 0.5 ± 0.2, the expression level of serum C19ORF5 protein in patients with effective chemotherapy was significantly lower than that in ineffective patients: 0.5 ± 0.2 vs. 0.8 ± 0.2, and there were statistical differences ( P<0.05). Conclusions:The high expression of C19ORF5 protein can increase the autophagy activity of colorectal cancer tissue; C19ORF5 protein regulates autophagy activity and is negatively correlated with the malignant degree of colorectal cancer; C19ORF5 protein may increase the sensitivity of paclitaxel chemotherapy by enhancing autophagy activity.
10.The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis
Pengfei LI ; Qiang JIAN ; Meina QIAO ; Changgui SUN ; Junfeng GAO
Journal of Pharmaceutical Practice 2020;38(4):368-372
Objective To study the clinical effect of Yaotongning capsule combined with etoricoxib for the pain and inflammation of lumbar vertebrae in elderly patients with lumbar osteoarthritis. Methods 120 elderly patients with lumbar osteoarthritis admitted to our hospital from January 2016 to June 2018 were randomly divided into the control group and the observation group, with 60 patients in each group. Patients in the control group were treated with etoricoxib, while patients in the observation group were treated with etoricoxib plus Yaotongning capsule orally. Both groups received medications for 2 weeks. Spinal pain and quality of life score changes were recorded. The inflammatory cytokines in serum TNF-α, GM-CSF, COX-2 and BMP-2 levels were monitored. The clinical efficacy was compared and drug safety profile was evaluated for two groups. Results The effective rates of the control group and the observation group were 78.33% and 91.67% respectively. The effective rate in the observation group weas significantly higher (P<0.05). After treatment, the VAS score for the patients in the observation group was significantly lower than that in the control group (P<0.05). The SF-36 score in the observation group was significantly increased (P<0.05), and the levels of TNF-α,GM-CSF and COX-2 in the serum were significantly lower than those in the control group (P<0.05), and the levels of BMP-2 were significantly increased (P<0.05). Conclusion Yaotongning capsule combined with etoricoxib in the treatment of senile lumbar osteoarthritis has definite curative effect. It significantly reduced lumbar pain, improved quality of life, inhibited inflammatory reaction, and had a better drug safety profile. The further clinical investigation for the combination therapy is warranted.

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