1.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
2.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
3.PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma
Ranran FENG ; Yilin GUO ; Meilin CHEN ; Ziying TIAN ; Yijun LIU ; Su JIANG ; Jieyu ZHOU ; Qingluan LIU ; Xiayu LI ; Wei XIONG ; Lei SHI ; Songqing FAN ; Guiyuan LI ; Wenling ZHANG
Journal of Pathology and Translational Medicine 2025;59(1):68-83
Background:
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods:
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results:
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.
4.The Influence of Family Adversities on Longitudinal Changes in Physical Inactivity Among Korean Adolescents During the COVID-19 Pandemic
Tae Kyoung LEE ; Jing ZHU ; Young Mi KIM ; Ze-Kai JIANG ; Meilin ZHANG ; Won Ha CHOI ; Tae-Young PAK ; Hana SONG
Journal of Preventive Medicine and Public Health 2024;57(5):443-450
Objectives:
Lack of physical activity has a critical effect on the physical and mental health of adolescents. This study examined the influence of family adversities on the longitudinal changes in physical inactivity among adolescents during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
The study used multi-wave data from the Korean Children and Youth Panel Survey, including 2590 Korean adolescents aged 12-14 years. The longitudinal trajectory of physical inactivity among adolescents and the effects of related factors were estimated using a latent growth modeling method.
Results:
Our results revealed a significant increase in physical inactivity among adolescents over time. At the onset of the pandemic, approximately one-seventh of Korean middle schoolers reported a lack of physical activity. However, 3 years later, during the quarantine, nearly one-fifth of these adolescents reported a significant increase in their physical inactivity. Initially, low level parental education was predictive of adolescents’ physical inactivity, but this effect diminished over time, becoming statistically insignificant by the end of the 3-year period. Moreover, the increase in physical inactivity over the 3 years was significantly influenced by parental rejection.
Conclusions
These findings suggest that adolescents who experience parental rejection are more likely to report an increase in sedentary behaviors in contexts such as the COVID-19 pandemic.
5.Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study
Shuchun WEI ; Chuan LIU ; Min CHEN ; Yanhui CAI ; Xiaohan WU ; Meilin CHEN ; Jixiang ZHANG ; Dan XIANG ; Zhongchun LIU ; Changqing JIANG ; Jie SHI ; Kaichun WU ; Weiguo DONG
Chinese Journal of Internal Medicine 2023;62(8):1000-1006
Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.
6.Research Progress of Anti-angiogenic Agents Combined with Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer.
Jingyi WANG ; Wenying PENG ; Meilin JIANG ; Lin WU
Chinese Journal of Lung Cancer 2021;24(3):196-203
Lung cancer has the highest incidence rate and mortality in China, even in the world, and non-small cell lung cancer (NSCLC) accounts for about 85%. The growth and metastasis of tumor depend on the generation of blood vessels, and anti-angiogenic therapy is playing an increasingly important role, however, no significant improvement was observed in the underwent anti-angiogenic agents used for patients alone. In recent years, the application of immune checkpoint inhibitor (ICI) has significantly improved the prognosis of some lung cancer patients, however, the objective response rate of patients receiving ICI alone is low. While anti-angiogenic agents and ICI both regulate the tumor immune microenvironment and have a potential synergistic mechanism, showing a bright prospect in the combined application of anti-tumor therapy. In this review, we focused on the research and application of anti-angiogenic agents in combination with ICI in advanced non-small cell lung cancer.
7.The application of Critical Care Chest Ultrasonic Evaluation-plus Protocol in the etiological diagnosis of dyspnea and/or hemodynamic instability caused by abdominal abnormality
Li LI ; Yuhang AI ; Song JIANG ; Yanxin ZHANG ; Chenghuan HU ; Meilin AI ; Xinhua MA ; Zhiyong LIU ; Lina ZHANG
Chinese Journal of Internal Medicine 2017;56(8):583-587
Objective To investigate the application of Critical Care Chest Ultrasonic Examination (CCUE)-plus (CCUE-plus) in the etiological diagnosis in patieuts with dyspnea and/or hemodynamic instability caused by abdominal abnormalities.Methods Patients who suffered from dyspnea and/or hemodynamic instability in the Department of Critical Care Medicine,Xiangya Hospital,Central South University from September 2013 to September 2016 were recruited in this study.A total of 255 consecutive patients completed CCUE within 2hrs of admission.If the diaphragm could not be seen in the routine phrenic points according to Bedside Lung Ultrasound Evaluation (BLUE) protocol,it would be found along midaxillary line and defined m-point.The 59 patients with altered diaphragmatic position (m-point was more than 2 cm higher than phrenic point) received sequential abdominal ultrasonography.The latter ultrasonographic findings were compared with CT results.Results There were 42 (71.19%) cases with positive findings of abdominal ultrasonography,including 18 cases of seroperitoneum,16 cases of intestinal obstruction and 8 cases combined.Compared with 56 patients who applied with CT exam,the abdominal ultrasonography revealed a sensitivity of 76.7% and a specificity of 100.0% to diagnose seroperitoneum (AUCRoc 0.917);whereas the sensitivity was 75.0% and the specificity was 90.9% (AUCRoc 0.778) to diagnose intestinal obstruction.Moreover,there were 44 (74.58%) patients with normal left ventricular systolic function;more than three quarters (46/59,77.97%) patients had pulmonary consolidation.Conclusion In patients with dyspnea and/or hemodynamic instability caused by abdominal abnormalities and altered diaphragmatic position in BLUE protocol,CCUE-plus protocol has a high positive predictive value of more than 90% in abdominal abnormality.The findings of abdominal ultrasonography may change therapeutic target from cardio-pulmonary optimization to relief of intestinal obstruction or drainage of seroperitoneum.
8.Biomechanical properties and biocompatibility of the L4/5lumbar spine fusion cage
Liang LI ; Meilin JIANG ; Dunxu ZHAO
Chinese Journal of Tissue Engineering Research 2015;(38):6109-6113
BACKGROUND:Lumbar spinal stenosis can result in lumbar nerve root pain and other symptoms or even disability, which seriously impacts people’s quality of life. Interbody fusion is the main clinical treatment. Studies have shown that an interspinous fusion cage is prone to have hairline fractures and loss of implant; therefore, biomechanical properties and biocompatibility of the interbody fusion cage at L4/5need to be studied.
OBJECTIVE:To analyze the stability of the interspinous fusion cage at L4/5, and to explore the biomechanical properties and biocompatibility of adjacent segments.
METHODS: Ten adult fresh frozen spine specimens were selected and divided into normal group and model group, with five specimens in each group. The specimens were numbered and placed in a special fixture. The interspinous fusion cage, made in Zhengzhou Cast Medical Instrument Co., Ltd., China, was implantedin vivo and fixed using a cage fixator made of Ti6AL-4V ELI.
RESULTS AND CONCLUSION:Artificial vertebral bodies had less strain changes than the normal vertebrae in different implantation positions in terms of central compression, anteflexion, rear protraction, lateroflexion (P < 0.05). During vertebral displacement under the maximum load of 500 N, the linear displacement and angular displacement in anteflexion, rear protraction, left lateral flexion, levorotation were decreased significantly in the model group than the normal group (P < 0.05). These findings indicate that the interspinous fusion cage can maximaly preserve the range of motion of the injured vertebral body, maintain the stability of the segment, and reduce the stress of the intervertebral disc.
9.Efficacy and safety comparison of different statins in elderly patients
Yahong CHEN ; Chenggong JIANG ; Meilin LIU ; Fang LIU ; Yan FAN
Chinese Journal of Cardiology 2014;42(11):910-915
Objective To compare the efficacy and safety of atorvastatin,rosuvastatin and xuezhikang capsule in elderly.Methods A total of 314 60-to-94-year-old (average (73.6 ± 7.9) years old) patients who were given different doses and types of statins were divided into three groups:the atorvastatin group (108 patients),the rosuvastatin group (104 patients) and the xuezhikang capsule group (102 patients).The serum TG,TC,LDL-C,HDL-C,ALT and CK were examined before and after the treatment which lasted for at least 4 weeks.All patients were divided into moderate risk group (13,12 and 21 patients respectively in 3 groups) ; high risk group (40,44 and 48 patients respectively in 3 groups) and very high risk group (55,48 and 33 patients respectively in 3 groups) according to guidelines on prevention and treatment of dyslipidemia in chinese adults (2007 version).The rate of reaching target goal and the dose when reaching target levels in different risk stratification groups were calculated and compared.Results Serum TC,LDL-C and non-HDL-C were significantly reduced after the 4-week-treatment in all the three groups (P < 0.01).Serum LDL-C level before and after treatment were (3.14 ± 0.78) mmol/L vs.(2.14 ±0.65) mmol/L in atorvastatin group (the arevage dose was (16.4 ± 4.8) mg/d),(2.92 ± 0.77)mmol/L vs.(1.96 ±0.55) mmol/L in rosuvastatin group (the arevage dose was (8.7 ±3.0) mg/d),and (2.70 ±0.62) mmol/L vs.(2.16 ±0.61) mmol/L in xuezhikang capsule group (the arevage dose was (0.9 ± 0.3) g/d).Among all the three groups of patients,the cases of reaching target levels of LDL-C were 13,11 and 20 in patients at moderate risk,were 38(95.0%),38(86.4%) and 40 (83.3%) in patients at high risk,and were 22(40.0%),30(62.5%) and 17(51.5%) in patients at very high risk.There were no statistical differences in the rate of reaching target levels of LDL-C,non-HDL-C and TC in the three groups and at different risks (P > 0.05).One patient in the atorvastatin group showed ALT level elevation > 3 times of the upper limit of normal value,there was no patient with CK level elevation > 5 times of the upper limit of normal value.Conclusion Atorvastatin,rosuvastatin and xuezhikang capsule at low dose and/or standard dose are effective and safety in elderly patients.
10.The clinical features of gastrointestinal bleeding complicating aortic stenosis
Fang LIU ; Chenggong JIANG ; Xueru FENG ; Meilin LIU
Chinese Journal of Internal Medicine 2013;52(9):753-756
Objective To deepen the understanding about Heyde's syndrome by investigating the clinical characteristics and prognosis of the patients with aortic valve stenosis complicating with gastrointestinal bleeding.Methods Patients with aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our hospital from 2001 to 2011 were retrieved and analyzed.Results In all the 443 157 in-patients,474 patients were diagnosed with aortic valve stenosis (0.11%,474/443 157) and 14 patients (9 males and 5 females,aged 53-87 years old) with gastrointestinal bleeding coincidently (2.95 %,14/474).Among the 14 patients,3 were moderate aortic valve stenosis,11 severe aortic valve stenosis.The aortic valve peak flow velocity was 324-709 (480.54 ± 188.25) cm/s and the mean aortic valve pressure gradient was 21.04-91.56 (56.93 ± 29.90) mm Hg (1 mm Hg =0.133 kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1 of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC) count were significantly lower than the normal range [(69 ±28) g/L and (2.71 ±2.04) × 1012/L,P <0.05].Their mean corpuscular volume(MCV),mean corpuscular hemoglobin (MCH),mean corpuscular hemoglobin concentration (MCHC),platelet (PLT) count,prothrombin time (PT) and international normalized ratio (INR) were in normal range [(90.21 ± 2.94) r,(29.39 ± 1.99) pg,(327.57 ± 14.82) g/L,(185.13 ±22.55) × 109/L,(11.4 ± 1.04) s and 1.22 ±0.44,respectively].Among all the 14 patients,13 were over 65 years old and they all accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was found in 6 patients with 4 lesions located in descending colon and 2 located in sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer,and another of duodenal ulcer,while no definite hemorrhage foci were found in the other 11 patients.A total of 6 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent gastrointestinal bleeding was ever found.Conservative treatment was performed in the other 5 patients with severe aortic valve stenosis (5/11) and resulted in sudden death in 2 patients (2/5).Conclusions Prompt echocardiography and gastrointestinal endoscopy should be performed in the elderly patients with obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment of Heyde's syndrome.AVR is a fundamental procedure to improve the prognosis of Heyde's syndrome.

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