1.Effects of superoxide dismutase inhibition of AFP expression on the malignant biological behavior of PLC/PRF/5 liver cancer cells
Yi CHEN ; Baoying CHEN ; Yuli ZHOU ; Haixia XU ; Yu CAO ; Yue GU ; Mingyue ZHU ; Mengsen LI
China Pharmacy 2025;36(17):2120-2126
OBJECTIVE To explore the effect of superoxide dismutase (SOD) administration on the malignant behavior of PLC/PRF/5 liver cancer cells, and analyze the correlation between SOD and alpha-fetoprotein (AFP) expression, to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02, AFP- negative human liver cancer cells HLE, and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP, SOD and activity of SOD in cells before and after changing AFP expression; the effects of different concentrations of SOD [0 (control), 0.188, 0.375, 0.75, 1.5, 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein (Src) in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group, the expression levels of SOD1 and SOD2, and SOD activity in PLC/PRF/5 cells were significantly reduced (P<0.05). After down-regulating AFP expression in PLC/PRF/ 5 cells, compared with PLC/PRF/5 group, the expression levels of SOD1 and SOD2, as well as SOD activity, were significantly increased in the PLC/PRF/5-shAFP group (low-expression) (P<0.05). After 48 hours of SOD treatment, compared with control group, the scratch healing rates of PLC/PRF/5 cells in the 0.375, 0.75, 1.5 and 3 U/mL SOD groups were significantly reduced (P<0.05); after 72 hours of SOD treatment, compared with control group, the scratch healing rates of PLC/PRF/5 cells in the 0.375, 0.75, and 1.5 U/mL SOD groups were significantly reduced (P<0.05 or P<0.01). Compared with control group, proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375, 0.75, 1.5 and 3 U/mL SOD groups (P<0.05 or P<0.01). Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression, the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups (over-expression) after up-regulating SOD1 and SOD2 expression were significantly reduced (P<0.05). CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells, and the expression level and activity of SOD are negatively correlated with AFP.
2.Preliminary study on predicting hepatic artery thrombosis formation and evaluating treatment efficacy with ultrasound hemodynamic parameters in transplanted liver
Yuchen YANG ; Yuli ZHU ; Wen SHEN ; Wenping WANG ; Huixiong XU ; Hong HAN
Chinese Journal of Ultrasonography 2024;33(2):106-111
Objective:To clarify the changes of intrahepatic ultrasound hemodynamics before and after hepatic artery thrombosis (HAT) after liver transplantation (LT), providing early warning and anticoagulation guidance to clinicians.Methods:The clinical data of patients who underwent liver transplantation at Zhongshan Hospital of Fudan University between June 2006 and October 2022 were retrospectively analyzed, 47 patients with a diagnosis of HAT confirmed by DSA (digital subtraction angiography) were included in the HAT group, and 71 patients without vascular complications were included in the non-HAT group. Differences in peak flow velocity (PSV), resistance index (RI), and portal vein velocity (PVV) were compared between the two groups. Logistic regression analysis was used to determine the relationship between postoperative PSV decline and HAT occurrence, while ROC curve were used to determine the critical value and evaluate the diagnostic efficacy. Patients with HAT were divided into well-treatment group and poor-treatment group according to whether the blood flow was restored after multiple surgeries or thrombolytic treatments. The changes of early intrahepatic hemodynamics after surgical or thrombolytic therapy were compared between the two groups.Results:①A decrease in PSV of the transplanted hepatic artery was measured 1 d before HAT, and PSV<0.39 m/s predicted thrombus formation with a sensitivity of 0.70, specificity of 0.86, and the AUC was 0.83. ②After treatment, PSV in the HAT group increased immediately, approaching the normal level on the 2nd day. In the well-treatment group, PSV and PVV reached normal levels on the first day after treatment, which were significantly higher than the corresponding values in the poor-treatment group ( P=0.030, 0.021). Conclusions:In the early stage after liver transplantation, a PSV<0.39 m/s is related to the occurrence of HAT thrombosis 1 d later. A significant increase in PSV on the first day after treatment indicates a good treatment response, and there is no need for further DSA re-examination or increasing the number of thrombolysis.
3.YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling
Sui HUA ; Deng WANLI ; Chai QIONG ; Han BING ; Zhang YULI ; Wei ZHENZHEN ; Li ZAN ; Wang TING ; Feng JILING ; Yuan MAN ; Tang QINGFENG ; Xu HONGXI
Journal of Pharmaceutical Analysis 2024;14(4):525-541
The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.
4.Research advances of esketamine in patients undergoing cardiovascular surgery
Hongyu HUO ; Lu CHE ; Yuli WU ; Yiqi WENG ; Wenli YU ; Jiangang XU
The Journal of Clinical Anesthesiology 2024;40(7):766-769
Esketamine is a spin isomer of ketamine,which has the triple effect of sedation,analge-sia and amnesia,and is superior to ablative ketamine in terms of efficacy,controllability.It has been widely used in anesthesia,emergency and critical care in Europe and America,and is mostly used for sedation,analgesia and antidepressant in China.Esketamine is used in cardiac surgery to maintain stable hemodynam-ics,reduce the secretion of inflammatory factors and relieve postoperative pain.Its sympathomimetic effect allows it to be used for the induction of anesthesia in patients with hemodynamic instability and acute heart attack.This paper reviews the recent advance in the clinical value and limitations of esketamine in the perio-perative period of cardiovascular surgery and provides a reference for clinicians to use esketamine in the perioperative period of cardiovascular surgery.
5.Professor Liu Qingquan's experience in treating acute and severe diseases from the perspective of virtual reality
Qianwei XU ; Yuli LIU ; Tengfei CHEN
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):86-88
Acute and critical illnesses pose a serious threat to people's lives and health,causing great difficulties for doctors to rescue them.As an important part of traditional Chinese medicine(TCM)clinical medicine,emergency medicine of TCM has formed its own unique and complete theoretical system and accumulated rich clinical experience in the long-term struggle against diseases by the unremitting efforts of generations of doctors.As a well-known contemporary expert in TCM clinical emergency treatment,Professor Liu Qingquan has been deeply involved in the front line of clinical work,and creatively proposed the theory of three states and three principles differentiation,providing a rapid and effective core idea for the treatment of contemporary acute and critical patients with TCM.
6.Effect of s-ketamine on perioperative myocardial injury in patients undergoing liver transplantation
Hongyu HUO ; Lu CHE ; Yuli WU ; Yiqi WENG ; Wenli YU ; Jiangang XU
Chinese Journal of Anesthesiology 2024;44(6):657-661
Objective:To evaluate the effect of s-ketamine on perioperative myocardial injury in patients undergoing liver transplantation.Methods:This was a prospective randomized controlled study. Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ patients, aged 18-64 yr, with New York Heart Association classⅠ-Ⅲ, undergoing elective liver transplantation with general anesthesia in our hospital from May to October 2023, were divided into 2 groups ( n=30 each) using a random number table method: s-ketamine group (group S) and control group (group C). In group S, s-ketamine was intravenously injected at a dose of 0.5 mg/kg after induction of anesthesia, followed by an infusion of 0.5 mg·kg -1·h -1 until the end of surgery. The equal volume of normal saline was given instead in group C. Central venous blood samples were collected after induction of anesthesia (T 0), at 30 min of anhepatic phase (T 1), 30 min of neopepatic phase (T 2), abdominal closure (T 3), 24 h after operation (T 4) and 72 h after operation (T 5) for determination of the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase-MB isoenzyme, N-terminal pro-B-type natriuretic peptide, tumor necrosis factor-α, interleukin-6 (IL-6), IL-10 and high-mobility group protein B1 by enzyme-linked immunosorbent assay. The occurrence of adverse cardiac events during surgery and within 24 h after surgery, postoperative mechanical ventilation time, time of intensive care unit stay, and postoperative length of hospital stay were recorded. Results:Compared with group C, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase-MB isoenzyme, N-terminal pro-B-type natriuretic peptide, tumor necrosis factor-α and IL-6 at T 2-5 and high-mobility group protein B1 at T 2-4 were significantly decreased, the concentrations of serum IL-10 were increased at T 2-5, the incidence of myocardial ischemia was decreased, the mechanical ventilation time was shortened ( P<0.05), and no significant change was found in the time of intensive care unit stay and postoperative length of hospital stay in S group ( P>0.05). Conclusions:Intraoperative usage of s-ketamine can inhibit the inflammatory responses and reduce perioperative myocardial injury in the patients undergoing liver transplantation.
7.Effect of esketamine on inflammatory cytokines and myocardial injury markers in pediatric patients undergoing living-donor liver transplantation
Lu CHE ; Yiqi WENG ; Mingwei SHENG ; Lili JIA ; Yuli WU ; Hongyu HUO ; Wenli YU ; Jiangang XU
Chinese Journal of Organ Transplantation 2024;45(5):337-342
Objective:To explore the effect of esketamine on inflammatory cytokines and myocardial injury markers in children undergoing living-donor liver transplantation (LT).Methods:Considering the inclusion criteria, 50 children with biliary atresia were selected for living donor LT. They were equally randomized into two groups of control (C) and esketamine (E) (25 cases each). Esketamine 0.5 mg/kg was administered to group E during induction and continued at a dose of 0.5 mg·kg –1·h -1 after an induction of anesthesia. Group C provided the same dose of 0.9% sodium chloride injection during induction and then continued to pumping until the end of the procedure. Basic profiles of two groups were recorded. Hemodynamic parameters, such as heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP), were monitored at 5 min of anesthesia induction (T 0), 30 min of anhepatic phase (T 1), immediately after repercussion (T 2), 30 min of neohepatic phase (T 3) and end of surgery (T 4) in both groups. Central venous blood samples were collected at T 0, T 1, T 3 and T 4. Serum levels of cardiac troponin I (cTnI), creatine kinase isoenzyme-MB (CK-MB) ,tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured. The incidence of adverse cardiac events, postoperative mechanical ventilation time, ICU stay and hospitalization length were compared. Results:As compared with T 0, mean arterial pressure (MAP) at T 2 declined markedly in group E [(48.6±12.7) mmHg (1 mmHg=0.133 kPa) vs (55.6±10.7) mmHg, P<0.001] and C [(39.3±8.0) mmHg vs (53.2±9.4) mmHg, P<0.001 ] ;As compared with T 0, the TNF-α and IL-6 spiked at T 3 in group C [169.0 (207.1) ng/L vs 43.8 (26.4) ng/L, (132.63±51.75) ng/L vs (51.79±17.83) ng/L, P<0.001] and E [78.5 (138.8) ng/L vs 43.8 (26.4) ng/L, (87.44±32.17) ng/L vs (51.79±17.83) ng/L, P<0.001 ] ; In group C, the concentration of myocardial injury markers CK-MB and cTnI rose at T 3/T 4 compared with T 0[T 3 vs T 0: 5.7 (5.4) μg/L vs 4.0 (3.5) μg/L, 0.09 (0.08) μg/L vs 0.02 (0.02) μg/L; T 4 vs T 0: 5.3 (5.0) μg/L vs 4.0 (3.5) μg/L, 0.07 (0.08) μg/L vs 0.02 (0.02) μg/L, P<0.001 ]. In group E, the levels of CK-MB and cTnI were higher at T 3/T 4 than those at T 0[T 3 vs T 0: 7.0 (5.0) μg/L vs 4.6 (2.1) μg/L, 0.06 (0.09) μg/L vs 0.03 (0.04) μg/L; T 4 vs T 0: 5.4 (4.9) μg/L vs 4.6 (2.1) μg/L, 0.03 (0.06) μg/L vs 0.03 (0.04) μg/L; P<0.001]. Compared with group C, the MAP of E rose at T 1/T 2/T 3 [(58.8±10.3) mmHg vs (53.3±8.6) mmHg, P=0.048; (48.6±12.7) mmHg vs (39.3± 8.0) mmHg, P=0.003; (55.8±7.4) mmHg vs (51.5±7.3) mmHg, P=0.044]. Compared with group C, TNF-α and IL-6 decreased in E at T 3/T 4[T 3: 78.5 (138.8) ng/L vs 169.0 (207.1) ng/L, P=0.010; (87.44±32.17) ng/L vs (132.63±51.75) ng/L, P=0.017. T 4: 62.3 (118.3) ng/L vs 141.3 (129.2) ng/L, P=0.001; (74.34±26.38) ng/L vs (100.59±30.40) ng/L, P=0.002]. Compared with group C, cTnI decreased in E at T 3/T 4[0.06 (0.09) μg/L vs 0.09 (0.08) μg/L, P=0.014; 0.03 (0.06) μg/L vs 0.07 (0.08) μg/L, P=0.003]. Compared with group C, the mechanical ventilation time in group E decreased [195 (120) min vs 315 (239) min, P<0.001]. Compared with group C, the incidence of severe hypotension [16%(4/25) vs 48% (12/25), P=0.015 ], bradycardia [12% (3/25) vs 36 % (9/25), P=0.047 ], myocardial ischemia [4 % (1 /25) vs 24 % (6/25), P=0.042 ] and premature ventricular contractions [0 vs 4 %(1/25), P=0.312 ] decreased in group E. Conclusion:Intraoperative dosing of esketamine may suppress inflammatory reactions and alleviate perioperative myocardial injury in children undergoing living-donor LT.
8.Influencing factors of medical exposure frequency for community residents
Yuli CAO ; Yinping SU ; Hui XU ; Quanfu SUN ; Jinsheng CHENG
Chinese Journal of Radiological Health 2023;32(2):119-124
Objective To obtain the medical exposure frequency data of residents through a questionnaire survey on mobile phone networks in the community, and to analyze the main influencing factors. Methods A snowball sampling method was used to expand the sampling from medical staff in a county hospital to the community. The questionnaire included personal information such as occupation category, type of medical insurance, and education level as well as basic radiation-related knowledge and medical exposure type and frequency of respondents received in 2021. A logistic regression model was used to analyze the influencing factors of medical exposure. Results A total of 223 respondents were investigated, and 12.56% of them received radiological diagnosis and radiotherapy in 2021. The proportion of males receiving medical exposure was significantly higher than that of females (19.64% vs 10.18%). The likelihood of the person receiving medical exposure increased considerably with age, with the proportion of residents receiving medical exposure at 20, 30, 40, and 50 years of age being 6.25%, 7.95%, 19.23%, and 33.33%, respectively. Of persons who received medical exposure, 57.14% underwent CT scans. Persons participating in the new rural cooperative medical system were likely less to receive radiological diagnosis and radiotherapy than urban workers and residents (OR = 0.55, CI:0.13-2.23, P > 0.05). Conclusion Questionnaire survey in the community can obtain more information about the medical exposure of residents, and age and type of medical insurance are important factors affecting the frequency of medical exposure.
9.Application of DNA methylation in detection of endometrial carcinoma in women with abnormal uterine bleeding at childbearing age
Xingping ZHAO ; Dabao XU ; Jiezhi MA ; Yingqin FU ; Binyu LI ; Xitong JIN ; Yuli LIU ; Pei LIU
Chinese Journal of Laboratory Medicine 2023;46(4):367-374
Objective:This work aims to explore the application value of cervical exfoliated cell DNA (Cysteine dioxygenase type 1, CDO1 and CUGBP Elav-like family member 4, CELF4) methylation in the detection of endometrial cancer in women of childbearing age. Methods:From November 2021 to October 2022, a prospective study was conducted on a total number of 517 reproductive-age women with abnormal uterine bleeding who had surgical indications for hysteroscopy at the Xiangya Third Hospital of Central South University. The cervical exfoliated cells were collected for cytology, HPV (human papillomavirus) and gene methylation detection before operation. Clinical information of patients, level of tumor-related biomarkers, and endometrial thickness of transvaginal ultrasound (TVS) were also collected. Single factor regression method was used to analyze the high-risk factors of endometrial cancer. Receiver operating characteristic curve analysis was used to obtain the area under the curve(AUC), focusing on the screening efficacy of gene methylation test for endometrial cancer in women of childbearing age.Results:The age, body mass index (BMI)≥25 kg/m 2, endometrial thickness≥11 mm, CDO1 m ΔCt≤8.4, CELF4 m ΔCt≤8.8, and double gene methylation were associated with endometrial cancer in women of childbearing age, 1.16(1.08-1.25), 4.33(1.89-10.31), 9.49(3.88-26.69), 69.62(25.70-224.36), 23.64(9.66-63.99), 87.39(24.83-555.05), all P<0.05. The AUC was 0.90 (95% CI 0.83-0.97) of CDO1 m/ CELF4 m in diagnosing endometrial carcinoma was higher than others factors, with sensitivity and specificity of 91.7% (95% CI 80.6%-100%) and 88.8% (95% CI 86.0%-91.6%). TVS combined with DNA methylation detection further improved the sensitivity to 95.8% (95% CI 87.8%-100%), but could not improve the specificity 68.0% (95% CI 63.8%-72.1%). Conclusions:For women of childbearing age with abnormal uterine bleeding or abnormal vaginal discharge, the accuracy of cervical cytology DNA methyl detection of endometrial cancer is better than other non-invasive clinical programs. DNA methylation combined with TVS can improve the sensitivity of detection.
10.Effect of hyperthermia on biological behavior of squamous cell carcinoma of the tongue by regulating ferroptosis pathway
Pei SHEN ; Yuli HAO ; Xuexiao ZHOU ; Yuan CONG ; Shengzhi WANG ; Yun SHAO ; Ting XU ; Shouyi LI
Chinese Journal of Radiation Oncology 2023;32(3):260-264
Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.


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