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.Stage-Based Intervention in Atherosclerosis Using the "Attacking,Supplementing,Dispersing,Dissipating" Method Based on the Accumulation Syndrome Theory
Yujie LUAN ; Chenlu YUAN ; Zizhen CHEN ; Yijun LIU ; Yi WEI ; Yuanhui HU
Journal of Traditional Chinese Medicine 2025;66(7):685-689
Atherosclerosis is a complex pathological condition resulting from lipid deposition, chronic inflammatory responses, and fibrosis, with a prolonged disease course and multifactorial etiology. Based on the traditional Chinese medicine (TCM) theory of accumulation syndrome, atherosclerosis can be classified under this category, with its pathogenesis involving phlegm, blood stasis, deficiency, and accumulation. This paper proposed a stage-based intervention strategy using the four therapeutic principles of "attacking, supplementing, dispersing, dissipating", and divided into six stages based on the pathological progression, including the stage of accumulation before formation, the stage of accumulation already formed, the stage of nucleus accumulation, the stage of nucleus accumulation decay, the stage of nucleus accumulation consolidation, and the stage of severe stenosis of nucleus. At different stages, the intervention focuses on reinforcing healthy qi and consolidating the root, tonifying the kidneys and spleen, dispersing and removing turbidity, removing phlegm stagnation, promoting qi circulation, dispersing accumulations and removing stasis, attacking accumulation and expelling stasis, directing the turbid downward and dispersing accumulation, and treatment would be adjusted based on specific symptoms, which provides a theoretical framework for the prevention and treatment of atherosclerosis with TCM.
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.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.
5.Construction and application of the criteria for drug utilization evaluation of low-dose rivaroxaban in atherosclerotic cardiovascular disease
Liang WU ; Wei WANG ; Yanghui XU ; Bo ZHU ; Yijun KE
China Pharmacy 2025;36(17):2176-2181
OBJECTIVE To construct and apply drug utilization evaluation (DUE) criteria for low-dose rivaroxaban in atherosclerotic cardiovascular disease (ASCVD) based on the dual pathway inhibition (DPI) antithrombotic therapy scheme, to promote clinical rational drug use. METHODS Based on the instructions and relevant guidelines of low-dose rivaroxaban (2.5 mg, bid), the Delphi method was used to establish the DUE criteria for low-dose rivaroxaban used in ASCVD. Weighted technique for order preference by similarity to an ideal solution method was used to determine the relative weights of each evaluation index, and the rationality of the filing medical records of discharged patients using low-dose rivaroxaban for ASCVD at Anqing Municipal Hospital from February 2024 to January 2025 was evaluated. RESULTS The established DUE criteria included 3 primary indicators (medication indications, medication process, medication results) and 11 secondary indicators (such as indications, contraindications, etc.). The higher weighted secondary indicators being contraindications (0.117 9) and indications (0.112 1). A total of 265 medical records were included for evaluation. The evaluation results showed that 192 cases (72.45%) had reasonable medical records, 69 cases (26.04%) had basic reasonable medical records, and 4 cases (1.51%) had unreasonable medical records; unreasonable types mainly included inappropriate combination therapy, inappropriate usage and dosage, inappropriate post- medication monitoring, and inappropriate drug switching, etc. CONCLUSIONS This study establishes a DUE criteria for low-dose rivaroxaban in ASCVD based on the DPI antithrombotic treatment regimen, and the evaluation results are intuitive, reliable, and quantifiable. The use of low-dose rivaroxaban in ASCVD patients in our hospital is relatively reasonable, but further management needs to be strengthened.
6.Value of ultrasound combined with elastography in evaluating inflammation grading in patients with chronic liver disease at S2 stage of liver fibrosis
Rui CHEN ; Yijun ZHENG ; Zhiling GAO ; Wei CHEN ; Biao SU ; Shuainan SHI ; Jia GUO
Academic Journal of Naval Medical University 2025;46(7):863-868
Objective To explore the application value of ultrasound combined with elastography in grading inflammation in patients with chronic liver disease at S2 stage of liver fibrosis.Methods Totally 51 patients who were hospitalized at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from Jan.2022 to Mar.2024 and underwent liver biopsy with pathological results indicating a stage of S2 liver fibrosis in chronic liver disease were enrolled.All patients underwent ultrasound-guided liver biopsy to obtain the stage of pathological liver fibrosis(S1 to S4)and the grade of liver inflammation(G0 to G4).In addition,all the patients were examined by ultrasound combined with elastography;and shear wave velocity(Vs),acoustic attenuation coefficient(ATT),liver fibrosis index(LFI),fibrosis-related index(F index),and inflammatory activity index(A index)were obtained.The correlation between ultrasound combined with elastography parameters and pathological inflammation grading was analyzed.Results According to the pathological inflammation grading,there were 15 cases in group G1,28 cases in group G2,and 8 cases in group G3.There were significant differences in F index,A index,Vs and ATT among the 3 groups(all P<0.05).Among them,F index,A index and Vs in group G1 were significantly lower than those in group G3(P=0.007,0.006,0.040),while ATT was significantly higher than that in group G3(P=0.005);and there was no significant difference in LFI among the 3 groups(P=0.373).Vs,ATT,F index and A index were correlated with pathological inflammation grade(r=0.404,-0.417,0.379,0.383;P=0.003,0.002,0.006,0.006).The mean plot showed that with the increase of pathological inflammation grade,the age of patients showed a linear upward trend,ATT showed a linear downward trend,and A index showed a linear upward trend.Vs was positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),γ-glutamyltransferase(GGT),total bilirubin,and direct bilirubin(DBil)(all P<0.05).ATT was negatively correlated with ALT,AST,GGT,and DBil(all P<0.05);and both F index and A index were positively correlated with ALT,AST,ALP,GGT,and DBil(all P<0.05).Conclusion Ultrasound combined with elastography can be used to evaluate the degree of inflammation in patients with chronic liver disease at S2 stage of liver fibrosis.
7.Rapid health technology assessment of the efficacy,safety and cost-effectiveness of vericiguat in the treatment of heart failure
Yijun KE ; Wei WANG ; Can HUANG ; Yong JIN ; Lamei QI
China Pharmacy 2024;35(15):1818-1824
OBJECTIVE To evaluate the efficacy, safety and cost-effectiveness of vericiguat in the treatment of heart failure (HF) by rapid health technology evaluation method, and provide reference for the selection and decision-making of clinical treatment plans. METHODS Chinese and foreign databases such as CNKI, PubMed and related health technology evaluation websites were searched by computer. Relevant researchers independently screened literature, extracted data, and comprehensively analyzed the results of the included literature based on literature quality evaluation. RESULTS A total of 17 pieces of literature were included, involving 12 systematic reviews/meta-analyses and 5 pharmacoeconomic studies. The effectiveness analysis showed: for HF patients, compared with placebo, vericiguat (10 mg/d) significantly improved the EuroQol five dimensions questionnaire (EQ-5D) index and decreased the rate of hospitalization due to HF (P<0.05). For heart failure with reduced ejection fraction (HFrEF) patients, vericiguat reduced the incidence of hospitalization due to HF compared with sodium-glucose cotransporter 2 inhibitor (SGLT2i)(P<0.05); compared with angiotensin-converting enzyme inhibitor, vericiguat significantly reduced the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF(P<0.05). For HFrEF patients with chronic kidney disease, vericiguat had a tendency to reduce the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF compared with neurohormone inhibitors. Safety analysis showed: vericiguat did not increase drug-related adverse reactions compared to placebo (P>0.05). Economic analysis showed: domestic studies indicated that vericiguat had a higher incremental cost-effectiveness ratio. CONCLUSIONS Vericiguat has good safety and efficacy in the treatment of HF but does not possess an economic advantage in the Chinese population.
8.Synchronous analysis of ankle coronal plane tilt angle and peripheral associated muscle load in semi-squat landing of paratroopers
Yijun WANG ; Lei WU ; Zhaobo ZHOU ; Yi WEI ; Xinyu HUANG ; Tao LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(7):498-503
Objective:To investigate the relationship between ankle stability and associated muscle load around the ankle and the effect of a parachute ankle brace (PAB) on ankle inversion and associated muscle load around the ankle during landing through the simulated paratrooper semi-squat landing field experiment.Methods:In August 2021, 37 male paratroopers were randomly selected as the study objects to perform parachute landing training in the semi-squat posture on the 1.5 m and 2.0 m jump platforms with or without PAB, respectively. The coronal plane tilt angle of ankle joint and the percentage of maximum voluntary contraction (MVC%) of associated muscles around ankle joint during the process were measured and correlation analysis was conducted. And the effect of wearing PAB on the coronal plane tilt angle of ankle joint and the associated muscles around the ankle joint was analyzed.Results:During the semi-squat landing, the MVC% of the tibialis anterior muscle, lateral gastrocnemius muscle and peroneus longus muscle were positively correlated with the ankle coronal plane tilt angle in paratroopers wearing and without wearing PAB, and the correlations were statistically significant ( P<0.05). At the same height, compared with those without PAB, the coronal plane tilt angle of the ankle joint decreased during semi-squat landing in paratroopers PAB, and the differences were statistically significant ( P<0.05). At the landing moment of the same height, compared with those without PAB, the MVC% of lateral gastrocnemius muscle decreased and the MVC% of peroneus longus muscle increased in paratroopers wearing PAB, and the differences were statistically significant ( P<0.05). After the landing moment until the standing stage (100-200 ms) at 1.5 m height, the MVC% of the tibialis anterior muscle decreased in paratroopers wearing PAB compared with those without PAB, and the differences were statistically significant ( P<0.05). In the post-standing stage (200 ms) at 2.0 m height, the MVC% of the tibialis anterior muscle decreased in paratroopers wearing PAB compared with those without PAB, and the difference was statistically significant ( P<0.05) . Conclusion:Wearing PAB can reduce the ankle coronal plane tilt angle, improve ankle stability, reduce the muscle load of the lateral gastrocnemius muscle at the moment of landing, and reduce the load of the tibialis anterior muscle after landing, but increase the peroneus longus muscle load at the moment of landing.
9.Efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears
Yuncong JI ; Jian XU ; Yunkang KANG ; Wenzhi BI ; Wei MA ; Dongqiang YANG ; Honglin CUI ; Pengfei FU ; Yijun LIU ; Jinxiang TIAN ; Biao GUO
Chinese Journal of Trauma 2024;40(3):236-242
Objective:To investigate the efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears (IMRCT).Methods:A retrospective case series study was performed on 11 IMRCT patients who were admitted to Affiliated Fuyang Hospital of Bengbu Medical University (Fuyang People′s Hospital) from May 2020 to June 2022, including 7 males and 4 females, aged 54-74 years [(62.6±7.3)years]. All the patients were treated with arthroscopic superior capsular reconstruction using composite patch graft combined with tenodesis of the long head of the biceps tendon. The Visual Analogue Scale (VAS), Acromiohumeral Distance (AHD), Constant-Murley score and University of California Los Angeles (UCLA) score and active range of motion of the shoulder joint before, at 6 months after surgery and at the last follow-up were compared. At the last follow-up, the integrity of reconstructed superior capsule and the long head of the biceps tendon was evaluated using MRI of the shoulder joint. Postoperative complications were observed.Results:All the patients were followed up for 13-39 months [16(13, 36)months]. The VAS score, AHD, Constant-Murley score, and UCLA score were 2(2, 3)points, (9.1±1.1)mm, (56.1±5.4)points, and (19.7±2.8)points respectively at 6 months after surgery, which were all significantly improved from those before surgery [6(5, 7)points, (5.1±1.2)mm, (37.9±2.2)points, and (11.8±1.2)points] ( P<0.05). The VAS score, AHD, Constant-Murley score, and UCLA score were 0(0, 1)points, (8.4±0.9)mm, (83.6±3.8)points, and (28.2±2.3)points respectively at the last follow-up, which were all significantly improved from those before surgery ( P<0.05). At the last follow-up, the VAS score or AHD were not significantly improved from those at 6 months after surgery ( P>0.05); Constant-Murley score and UCLA score were both significantly improved from those at 6 months after surgery ( P<0.05). At 6 months after surgery, shoulder active ranges of motion in forward flexion, abduction and external rotation were (134.6±13.5)°, (124.6±18.6)° and 45(40, 50)° respectively, which were all significantly improved compared with those before surgery [(63.2±36.1)°, (65.0±23.1)°, and [30(20, 40)°] ( P<0.05). At the last follow-up, shoulder active ranges of motion in forward flexion, abduction and external rotation were (144.1±12.6)°, (139.6±15.4)° and 60(45, 65)° respectively, which were all significantly improved compared with those before surgery ( P<0.05). There were no significant differences in active range of motion of the shoulder in forward flexion, abduction and external rotation between 6 months after surgery and the last follow-up ( P>0.05). At the last follow-up, MRI revealed integrity of the reconstructed superior joint capsule and the long head of the biceps tendon in 10 patients. One patient developed resorption of the greater tuberosity and 1 showed a partial tear of the supraspinatus tendon at 1 year after surgery. Conclusion:Arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon can relieve shoulder pain, decrease upward displacement of the humerus head, improve the function and range of motion of the shoulder joint, and reduce complications in the treatment of IMRCT.
10.The application value of spectral CT venography in the display and staging of deep venous thrombosis in the lower extremity
Shigeng WANG ; Yijun LIU ; Xin FANG ; Beibei LI ; Xu WANG ; Zhiming MA ; Xiaoyu TONG ; Yong FAN ; Wei WEI ; Anliang CHEN
Journal of Practical Radiology 2024;40(3):478-482
Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.

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