1.Distribution characteristics of pathogens and influencing factors analysis of infections within 90 days after liver transplantation
Huabin PENG ; Haofeng XIONG ; Fei HOU ; Shuang ZHAO ; Yizhi ZHANG ; Tingting CUI ; Zhiying HE ; Jingyi LIU ; Liying SUN
Organ Transplantation 2026;17(2):212-226
Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4+T cells and CD8+T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4+T cells and CD8+T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4+T cells and CD8+T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.
2.Current status of diagnosis and treatment of steroid resistant acute rejection after liver transplantation
Organ Transplantation 2025;16(1):156-162
After the occurrence of acute rejection following solid organ transplantation, high-dose glucocorticoid (steroid) pulse therapy is commonly used. However, high-dose steroid pulse therapy is ineffective for some patients, leading to steroid resistant acute rejection, which may easily result in graft loss and severely affect patient prognosis. It is currently believed that both cell-mediated rejection and antibody-mediated rejection are involved in the occurrence and development of steroid resistant acute rejection. The diagnosis and treatment of steroid resistant acute rejection after kidney transplantation have become relatively mature, while the focus on steroid resistant acute rejection after liver transplantation has been relatively low in the past in China, and a unified standardized treatment plan has not yet been formed. Therefore, this article reviews the pathogenesis, diagnosis, and treatment of steroid resistant acute rejection after liver transplantation, in order to provide a reference for the diagnosis and treatment of steroid resistant acute rejection after liver transplantation.
3.Therapeutic Effect of Cranial Painkiller Pills' Extract Powder in Treatment of Trigeminal Neuralgia Induced by Injection of Talci Pulvis into Infraorbital Foramen of Model Rats Based on OTULIN-regulated Neuroinflammation
Shuran LI ; Xinwei WANG ; Jing SUN ; Dan XIE ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Jingsheng ZHANG ; Yaxin WANG ; Xihe CUI ; Xinying LI ; Bing HAN ; Tianjiao LU ; Xiaolan CUI ; Liying LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):21-28
ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis, evaluate its potential clinical application value, and compare the therapeutic effect with that of Cranial Painkiller granules, so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis, and the rats were randomly divided into the normal group, model group, carbamazepine group (60 mg·kg-1), Cranial Painkiller granules group (2.70 g·kg-1), and low, medium, and high dosage groups of Cranial Painkiller pills' extract powder (1.35, 2.70, 5.40 g·kg-1) according to the basal mechanical pain thresholds, and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling, and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin (HE) staining was used to detect pathological changes in the trigeminal ganglion, and enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in rat serum, as well as neuropeptide substance P (SP) and β-endorphin (β-EP) levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3, ASC, Caspase-1, and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group, the pain threshold of rats in the model group showed a continuous significant decrease (P<0.01). The pathological damage of brain tissue was significant (P<0.01), and the inflammatory levels of IL-1, IL-6, IL-8, and TNF-α in serum were significantly elevated (P<0.01). The level of the SP in the brain tissue was significantly elevated (P<0.01), and the level of β-EP was significantly reduced (P<0.01), while the level of OTULIN was significantly reduced, and NLRP3, ASC, and Caspase-1 protein levels were significantly elevated (P<0.01). After administration of the drug, compared with the model group, the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased (P<0.01). The inflammatory levels of IL-1, IL-6, IL-8, and TNF-α and SP levels significantly decreased (P<0.01), and the β-EP levels were significantly elevated (P<0.01), while the levels of OTULIN protein were significantly elevated (P<0.05, P<0.01), and the levels of NLRP3, ASC proteins were decreased (P<0.01)in high dose Cranial Painkiller pills' extract powder. Meanwhile, compared with those in the model group, the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement (P<0.05, P<0.01). ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis, and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.
4.Therapeutic Effect of Cranial Painkiller Pills' Extract Powder in Treatment of Trigeminal Neuralgia Induced by Injection of Talci Pulvis into Infraorbital Foramen of Model Rats Based on OTULIN-regulated Neuroinflammation
Shuran LI ; Xinwei WANG ; Jing SUN ; Dan XIE ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Jingsheng ZHANG ; Yaxin WANG ; Xihe CUI ; Xinying LI ; Bing HAN ; Tianjiao LU ; Xiaolan CUI ; Liying LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):21-28
ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis, evaluate its potential clinical application value, and compare the therapeutic effect with that of Cranial Painkiller granules, so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis, and the rats were randomly divided into the normal group, model group, carbamazepine group (60 mg·kg-1), Cranial Painkiller granules group (2.70 g·kg-1), and low, medium, and high dosage groups of Cranial Painkiller pills' extract powder (1.35, 2.70, 5.40 g·kg-1) according to the basal mechanical pain thresholds, and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling, and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin (HE) staining was used to detect pathological changes in the trigeminal ganglion, and enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in rat serum, as well as neuropeptide substance P (SP) and β-endorphin (β-EP) levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3, ASC, Caspase-1, and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group, the pain threshold of rats in the model group showed a continuous significant decrease (P<0.01). The pathological damage of brain tissue was significant (P<0.01), and the inflammatory levels of IL-1, IL-6, IL-8, and TNF-α in serum were significantly elevated (P<0.01). The level of the SP in the brain tissue was significantly elevated (P<0.01), and the level of β-EP was significantly reduced (P<0.01), while the level of OTULIN was significantly reduced, and NLRP3, ASC, and Caspase-1 protein levels were significantly elevated (P<0.01). After administration of the drug, compared with the model group, the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased (P<0.01). The inflammatory levels of IL-1, IL-6, IL-8, and TNF-α and SP levels significantly decreased (P<0.01), and the β-EP levels were significantly elevated (P<0.01), while the levels of OTULIN protein were significantly elevated (P<0.05, P<0.01), and the levels of NLRP3, ASC proteins were decreased (P<0.01)in high dose Cranial Painkiller pills' extract powder. Meanwhile, compared with those in the model group, the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement (P<0.05, P<0.01). ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis, and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.
5.Predictive value of preoperative combined detection of NLR and PTAR for early abdominal infection after liver transplantation
Huabin PENG ; Ying LIU ; Fei HOU ; Shuang ZHAO ; Yizhi ZHANG ; Tingting CUI ; Zhiying HE ; Jingyi LIU ; Haofeng XIONG ; Liying SUN
Organ Transplantation 2025;16(6):931-943
Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.
6.Paroxetine alleviates dendritic cell and T lymphocyte activation via GRK2-mediated PI3K-AKT signaling in rheumatoid arthritis.
Tingting LIU ; Chao JIN ; Jing SUN ; Lina ZHU ; Chun WANG ; Feng XIAO ; Xiaochang LIU ; Liying LV ; Xiaoke YANG ; Wenjing ZHOU ; Chao TAN ; Xianli WANG ; Wei WEI
Chinese Medical Journal 2025;138(4):441-451
BACKGROUND:
G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA).
METHODS:
The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism.
RESULTS:
In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells.
CONCLUSION
Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism*
;
Arthritis, Rheumatoid/immunology*
;
Animals
;
Dendritic Cells/metabolism*
;
Paroxetine/therapeutic use*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Mice
;
Humans
;
Mice, Inbred C57BL
;
Signal Transduction/drug effects*
;
Male
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Lymphocyte Activation/drug effects*
;
Female
;
T-Lymphocytes/metabolism*
;
Middle Aged
7.Prediction of Spatial Distance of CAFs-TAECs for Pathological Response to Neoadjuvant Chemoimmunotherapy in Lung Squamous Cell Carcinoma.
Duming YE ; Liying YANG ; Yimin ZHAO ; Yinhui WEN ; Miaoqing ZHAO ; Ligang XING ; Xiaorong SUN
Chinese Journal of Lung Cancer 2025;28(8):576-584
BACKGROUND:
Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC.
METHODS:
We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort.
RESULTS:
Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000.
CONCLUSIONS
CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans
;
Lung Neoplasms/therapy*
;
Neoadjuvant Therapy
;
Male
;
Female
;
Middle Aged
;
Retrospective Studies
;
Endothelial Cells/drug effects*
;
Aged
;
Cancer-Associated Fibroblasts/drug effects*
;
Immunotherapy
;
Carcinoma, Squamous Cell/drug therapy*
;
Carcinoma, Non-Small-Cell Lung/drug therapy*
;
Adult
8.Artificial intelligence iterative reconstruction combined with 60kVp scanning for craniocervical CT angiography
Qizhong SUN ; Ting MENG ; Liying PENG ; Yicheng HAN ; Ximing WANG
Chinese Journal of Medical Imaging Technology 2025;41(4):520-524
Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)combined with 60 kVp scanning in craniocervical CT angiography(CTA).Methods Eighty-six patients with suspected craniocervical vascular diseases were prospectively enrolled and randomly received routine-dose(120 kVp)or low-dose(60 kVp)scanning(each n=43),and contrast dosage and radiation dose were recorded.After scanning,hybrid iterative reconstruction(HIR)was used to reconstruct routine-dose images(group A),while HIR images(group B1)and AIIR images(group B2)were performed to reconstruct low-dose images,respectively.The overall imaging quality,visualization of targeted large and small vessels and diagnostic confidence scores,as well as image noise(SD),signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of targeted large vessels were compared among 3 groups.Results Contrast dosage and effective dose(ED)decreased by 36.52% and 77.56% in low-dose scanning compared with those in routine-dose scanning,respectively.No significant difference of subjective scoring of imaging quality indexes was found between groups B2 and A(all adjusted P>0.05),which were both higher than those in group B1(all adjusted P<0.05).SD of target large vessels in group B2 than that of most target large vessels in group A(all adjusted P<0.05)except for aortic arch.SNR and CNR of target large vessels in group B2 were higher than those in group A and B1(all adjusted P<0.05),while SD of target large vessels in group B2 were lower than in group B1.Conclusion AIIR combined with 60 kVp scanning in craniocervical CTA could meet diagnostic requirements of imaging quality and reduce contrast dosage and radiation dose.
9.Artificial intelligence iterative reconstruction for low-dose chest CT images of infants with congenital heart disease
Minghua SUN ; Liying PENG ; Feifei ZHANG ; Yukun PAN ; Tong LI ; Jiliang ZHANG ; Ruigang XIE ; Yinghui GE
Chinese Journal of Medical Imaging Technology 2025;41(4):525-529
Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)for low-dose chest CT images of infants with congenital heart disease.Methods Totally 262 infants with congenital heart disease who would undergo chest CT scanning were prospectively enrolled and randomly divided into low-dose group(n=142)and conventional dose group(n=120).Chest CT scanning with tube voltage of 80 kVp and tube current of 10 mAs was performed in low-dose group,and hybrid iterative reconstruction(HIR,group A)and AIIR(group B)were used to reconstruct images,respectively.In conventional dose group,chest CT scanning with tube voltage of 80 kVp and tube current of 100 mAs was performed,and HIR was used to reconstruct images(group C).Then subjective and objective evaluation on image quality were performed,the results were compared among 3 groups,and the value of AIIR was analyzed.Results Significant differences of image quality and clarity of displaying structures were found among 3 groups(all P<0.001).Among them,except for the clarity of interlobar fissure,no significant difference of subjective scores was found between low-dose AIIR images and conventional dose HIR images(all corrected P>0.05),while subjective scores of low-dose HIR images were all lower than those of low-dose AIIR images and conventional dose HIR images(all corrected P<0.05).Significant differences of standard deviation(SD),signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were found among 3 groups(all P<0.001)and between each 2 groups(all corrected P<0.05).The effective dose of low-dose group and conventional dose group was 0.09(0.08,0.10)and 0.85(0.75,1.03)mSv,respectively,and the former was lower than the latter(Z=-13.942,P<0.001).Conclusion Using AIIR could obtain low-dose chest CT images of infants with quality comparable to conventional chest CT images.
10.Effects of KLK5 overexpression on growth of subcutaneous xenograft tumor and cisplatin sensitivity in nude mice
Rongmian YAN ; Xinting SUN ; Xin GUAN ; Yu CHENG ; Liying HAN
Journal of Jilin University(Medicine Edition) 2025;51(5):1194-1203
Objective:To discuss the effects of kallikrein 5(KLK5)overexpression on the proliferation,invasion and cisplatin(DDP)sensitivity of cervical cancer cells,and to clarify its mechanism.Methods:Western blotting method was used to verify the stable transfection and overexpression of KLK5 in the cervical cancer cell(ME180-OE-KLK5).The cervical cancer ME180-NC-KLK5 and ME180-OE-KLK5 cells in logarithmic growth phase were subcutaneously inoculated into the nude mice to establish the subcutaneous xenograft models.After successful modeling,the mice were randomly divided into normal saline control group(NC-KLK5+0.9%NaCl group),DDP treatment group(NC-KLK5+DDP group),KLK5 overexpression group(OE-KLK5+0.9%NaCl group)and KLK5 overexpression combined with DDP group(OE-KLK5+DDP group),with 5 mice in each group.The nude mice in NC-KLK5+DDP group and OE-KLK5+DDP group were given intraperitoneal injection of DDP at a dose of 5 mng·kg-1;the nude mice in NC-KLK5+0.9%NaCl group and OE-KLK5+0.9%NaCl group were given intraperitoneal injection of normal saline at a dose of 0.01 mL·g-1.The body weights of nude mice were measured every 2 d,and the long diameter and short diameter of the tumors were recorded to calculate the tumor volume and plot the tumor growth curve.At 24 h after the last administration on day 14,the nude mice were sacrificed,and the tumors were dissected and weighed.HE staining method was used to observe the pathomorphology of tumor tissue in the nude mice in various groups;immunohistochemistry staining method was used to observe the expression levels of KLK5,Ki67 and matrix metalloproteinase-9(MMP-9)proteins in the tumor tissues of the nude mice in various groups.Results:Compared with ME180-NC-KLK5 cells,the expression level of KLK5 protein in ME180-OE-KLK5 cells was increased(P<0.05).In the first week after subcutaneous xenograft inoculation,the nude mice in various groups showed good feeding and activity status,and their body weights gradually increased.The drug administration phase started from the second week.During the drug treatment period,the feeding and activity status as well as body weight of the nude mice in NC-KLK5+0.9%NaCl group showed no significant changes compared with the first week;compared with NC-KLK5+0.9%NaCl group,the nude mice in NC-KLK5+DDP group began to show loss of appetite,no increase in body weight,and decreased activity.During the drug treatment period in the third week,the feeding and activity status of the nude mice in NC-KLK5+0.9%NaCl group showed no significant changes compared with the second week,while they began to show no increase in body weight;compared with NC-KLK5+0.9%NaCl group,the feeding and activity status of the nude mice in NC-KLK5+DDP group were significantly weakened,and their body weights decreased.Compared with NC-KLK5+0.9%NaCl group,the volume of xenograft tumor in NC-KLK5+DDP group was decreased(P<0.01);compared with NC-KLK5+DDP group,the volume of xenograft tumor OE-KLK5+DDP group was significantly increased(P<0.001);compared with NC-KLK5+0.9%NaCl group,the volume of xenograft tumor of the nude mice in OE-KLK5+0.9%NaCl group was increased(P<0.001);compared with OE-KLK5+0.9%NaCl group,the volume of xenograft tumors in the nude mice in OE-KLK5+DDP group showed no statistically significant difference(P>0.05).Compared with NC-KLK5+0.9%NaCl group,the weight of xenograft tumor of the nude mice in NC-KLK5+DDP group was decreased(P<0.05);compared with NC-KLK5+DDP group,the weight of xenograft tumors of the nude mice in OE-KLK5+DDP group was significantly increased(P<0.001);compared with NC-KLK5+0.9%NaCl group,the weight of xenograft tumor of the nude mice in OE-KLK5+0.9%NaCl group was increased(P<0.001);compared with OE-KLK5+0.9%NaCl group,the weight of xenograft tumors of the nude mice in OE-KLK5+DDP group showed no statistically significant difference(P>0.05).Compared with NC-KLK5+0.9%NaCl group,the xenograft tumor cells of the nude mice in OE-KLK5+0.9%NaCl group showed greater nuclear heterogeneity;the xenograft tumor cells of the nude mice in OE-KLK5+DDP group and NC-KLK5+DDP group showed cytomorphological changes,manifested as nuclear pyknosis and fragmentation,reduced cell volume,and the appearance of necrosis and apoptosis.Compared with NC-KLK5+DDP group,the degree of necrosis in xenograft tumor of the nude mice in OE-KLK5+DDP group was more pronounced.Compared with NC-KLK5+0.9%NaCl group,the expression levels of KLK5,Ki67 and MMP-9 proteins in xenograft tumor tissue of the nude mice in NC-KLK5+DDP group were decreased(P<0.05);compared with NC-KLK5+DDP group,the expression levels of KLK5,Ki67,and MMP-9 proteins in xenograft tumor tissue of the nude mice in OE-KLK5+DDP group were increased(P<0.001);compared with NC-KLK5+0.9%NaCl group,the expression levels of KLK5,Ki67 and MMP-9 proteins in xenograft tumor tissue of the nude mice in OE-KLK5+0.9%NaCl group were increased(P<0.001);compared with OE-KLK5+0.9%NaCl group,the expression levels of KLK5,Ki67 and MMP-9 in xenograft tumor tissue of the nude mice in OE-KLK5+DDP group showed no statistically significant differences(P>0.05).Conclusion:KLK5 overexpression can promote the growth of subcutaneous xenograft tumors of cervical cancer ME 180 cells treated with DDP,up-regulate the expressions of Ki67 and MMP-9 in the xenograft tumor tissue,and reduce the sensitivity of the xenograft tumor to DDP.

Result Analysis
Print
Save
E-mail