1.Zanubrutinib inhibits macrophage infiltration to ameliorate renal fibrosis after renal ischemia-reperfusion injury
Qi LIU ; Yannan ZHANG ; Qiquan SUN
Organ Transplantation 2025;16(4):545-555
Objective To explore the action mechanism of Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib on renal fibrosis after renal ischemia-reperfusion injury (RIRI). Methods C57BL/6 mice were randomly divided into sham operation group, modeling group and modeling + zanubrutinib treatment group (zanubrutinib group), with 5 mice in each group. The groups underwent sham operation, RIRI modeling and RIRI modeling + zanubrutinib (5 mg/kg) treatment, respectively. Tissues were collected after 21 days. The morphological changes of the kidneys, histopathological changes, levels of M1 macrophages in the kidneys, inflammatory responses in the kidneys, and the expression of related inflammatory signaling pathways of macrophages induced by lipopolysaccharide(LPS) + interferon(IFN)-γ in vitro after lentivirus transfection were observed. Results Compared with the sham operation group, the kidneys of the modeling group mice shrank, the ratio of unilateral kidney weight to mouse body weight decreased, renal tubular interstitial fibrosis worsened, and the expression of α-smooth muscle actin (α-SMA) and type I collagen in the kidneys increased. The expression of F4/80 and CD86 in the kidneys increased, the lumen of the renal proximal convoluted tubules was significantly dilated, cellular debris accumulated in the lumen and inflammatory cell infiltration occurred, and the messenger RNA (mRNA) levels of CD86, tumor necrosis factor (TNF)-α, interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and IL-1β in the kidneys increased. Compared with the modeling group, the kidneys of the zanubrutinib group mice enlarged after RIRI, the ratio of unilateral kidney weight to mouse body weight increased, renal tubular interstitial fibrosis was alleviated, and the expression of α-SMA and type I collagen in the kidneys decreased. The expression of F4/80 and CD86 in the kidneys decreased, the number of CD45+ lymphocytes and CD11b+ F4/80+ macrophages in the kidneys decreased, the infiltration of CD11b+ F4/80+ and CD86+ macrophages in the damaged tissue decreased, the degree of renal inflammatory pathological changes was milder, and the mRNA levels of CD86, TNF-α, IL-6, iNOS and IL-1β in the kidneys decreased. In vitro experiments using LPS+IFN-γ to induce M1-type macrophages found that the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and nuclear factor (NF)-κB increased, while the phosphorylation levels decreased after BTK knockdown, indicating that BTK knockdown may inhibit the PI3K/Akt and NF-κB related inflammatory signaling pathways, thereby reducing the pro-inflammatory effects of LPS+IFN-γ induced M1-type macrophages. Conclusions Zanubrutinib may alleviate renal fibrosis after RIRI by inhibiting the PI3K/Akt and NF-κB related inflammatory signaling pathways, reducing the infiltration of M1 macrophages and the expression of related inflammatory factors, providing potential evidence for its clinical application.
2.Research progress on association between macrophages and ischemia-reperfusion injury
Qi LIU ; Yannan ZHANG ; Qiquan SUN
Organ Transplantation 2024;15(1):40-45
Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.
3.Analysis of factors affecting the detection of urinary stone using virtual unenhanced images derived from dual-energy CTU
Yannan CHENG ; Yanan LI ; Jingtao SUN ; Qian TIAN ; Jian YANG ; Wei TONG ; Jian YANG ; Jianxin GUO
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):535-541
Objective To evaluate the factors affecting urinary stone detection rate using virtual unenhanced(VUE)images obtained from triphasic dual-energy CT urography(DECTU)based on Logistic regression analysis.Methods For this study,150 patients who had suspected urinary stone and underwent triphasic DECTU were included.The true unenhanced(TUE)images were reconstructed as 120 kVp-like images,and VUE images at the portal venous phase[VUE(VP)]and excretory phase[VUE(EP)]were obtained using iodine removal technique from portal venous and excretory phase DECTU images,respectively.Two readers independently evaluated the above three types of images,and recorded the number of urinary stones,their anatomical locations,and whether there was residual iodine on the VUE images.Stone size and CT number were recorded only on the TUE images.Stone size,CT number,anatomical location,and iodine contrast agent were included in univariate and multivariate Logistic regression analyses to evaluate the factors affecting urinary stone detection rate using VUE images.Thresholds for detecting urinary stones on VUE images were determined using receiver operating characteristics(ROC)analysis.Results We detected 304 stones on TUE images,while the detection rates were 92.4%and 71.4%when using VUE(VP)and VUE(EP)images,respectively.Stone size and CT number were important factors influencing urinary stone detection rate using VUE(VP)and VUE(EP)images(P<0.01).The area under curve(AUC)of using stone size and CT number for detecting stones using the VUE(VP)images was up to 0.96,and as threshold values,stones with size larger than 3.52 mm and CT number greater than 469 HU were found to have high accuracy.However,the AUC decreased to 0.88 when we combined stone size,CT number and anatomical location using the VUE(EP)images.In addition,different contrast agents did not affect the detection rate of stones on the VUE(EP)images(P=0.57).The stone detection rate in the kidney was significantly lower than those on the VUE(EP)images(P<0.001).Conclusion VUE(VP)images provide better stone detection.Stone size and CT number have significant impacts on the stone detection rate using VUE images.The lower stone detection rate in the kidney on the VUE(EP)images is related to the residual iodine.
4.A meta-analysis of related factors of aggressive behavior in hospitalized Chinese patients with schizophrenia
Yannan JIA ; Yuqiu ZHOU ; Yujing SUN ; Wenlong JIANG ; Xiangguo SUN ; Shuang WANG
Chinese Mental Health Journal 2024;38(8):654-659
Objective:To systematically review the factors related to the aggressive behavior of hospitalized patients with schizophrenia in China.Methods:CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Cochrane Library,and Embase databases were searched to collect case-control studies on factors related to aggression in hospitalized patients with schizophrenia in China from its inception to June 2023.Analysis was per-formed using ReviewManager 5.3 to calculate pooled OR(95%CI)values.Results:Thirty-three studies were in-cluded.Medical staff coercive measures(OR=3.86,95%CI:2.75-5.43),unemployment(OR=1.44,95%CI:1.14-1.81),positive family history(OR=2.97,95%CI:2.29-3.87),poor medication compliance(OR=4.37,95%CI:3.36-5.69),young age(OR=3.13,95%CI:2.66-3.69),involuntary hospitalization(OR=3.34,95%CI:2.81-3.97),depression(OR=2.11,95%CI:1.68-2.66),emotional abuse(OR=1.13,95%CI:1.04-1.23),male(OR=2.70,95%CI:2.20-3.31),delusions(OR=2.14,95%CI:1.69-2.71),auditory hallucina-tions(OR=2.23,95%CI:1.70-2.94),and major life events(OR=3.21,95%CI:1.90-5.42)and previous history of aggressive behavior(OR=2.20,95%CI:2.06-2.34)were risk factors associated with aggressive be-havior in Chinese patients with schizophrenia,and social support(OR=0.46,95%CI:0.31-0.67)was a protec-tive factor.Conclusion:There are various factors related to aggressive behavior in hospitalized Chinese patients with schizophrenia,and medical staff should identify high-risk groups early according to the relevant factors,and effec-tively intervene in controllable factors to reduce the occurrence of aggressive behavior.
5.Clinical application of mammogram microcalcification detection model based on Attention U-Net
Xiaoqi SUN ; Siqing CAI ; Yannan REN
Chinese Journal of Medical Physics 2024;41(6):716-723
Objective To develop a mammogram microcalcification detection model(DL model)based on Attention U-Net for realizing the efficient detection of microcalcifications,and to investigate the effects of breast density and microcalcification type on the microcalcification detection performance of the DL model.Methods A retrospective analysis was performed on 694 images from 347 patients undergoing mammography.Through the independent image diagnosis by junior physicians and review by senior physicians,the reference standard for microcalcification detection was established.Neural network training was performed to establish a DL model.The performance of the model for microcalcification detection was evaluated using precision rate,recall rate,intersection over union(IoU)and F1-score which were calculated based on calcification area or quantity;and the effects of microcalcification type(benignvsmalignant)and breast density(a+bvsc+d)on the model performance were also analyzed.Results For detecting microcalcifications by the DL model,the precision rate,recall rate,IoU and F1-score were 85.12%±18.39%,78.18%±19.25%,68.29%±21.39%and 78.96%±17.70%when the calculation was based on calcification area,and those were 76.72%±19.85%,85.12%±18.39%,67.13%±23.84%and 77.65%±9.37%when the calculation was based on calcification quantity.The differences in precision rate,recall rate,IoU,F1-score of DL model in different microcalcification types(benignvsmalignant)and breast densities(a+bvsc+d)were insignificant.Conclusion The developed mammogram microcalcification detection model based on Attention U-Net can effectively detect breast microcalcifications and is conducive to the quantitative research on breast microcalcifications.Meanwhile,the model exhibits high stability,and the breast density and microcalcification type have trivial effects on the microcalcification detection performance of the model.
6.Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study.
Lanlan CHEN ; Zhongqi FAN ; Xiaodong SUN ; Wei QIU ; Wentao MU ; Kaiyuan CHAI ; Yannan CAO ; Guangyi WANG ; Guoyue LV
Chinese Medical Journal 2023;136(7):840-847
BACKGROUND:
Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown.
METHODS:
We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines.
RESULTS:
The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy.
CONCLUSIONS
The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans
;
Mendelian Randomization Analysis
;
Irritable Bowel Syndrome
;
Colorectal Neoplasms/genetics*
;
Cholelithiasis/complications*
;
Cholecystectomy/adverse effects*
;
Genome-Wide Association Study
;
Polymorphism, Single Nucleotide
7.Application of deep learning image reconstruction algorithm in low-dose abdominal CT
Yannan CHENG ; Jingtao SUN ; Yanan LI ; Yinxia GUO ; Le CAO ; Jian YANG ; Jian YANG ; Jianxin GUO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):466-472
【Objective】 To investigate the value of deep learning image reconstruction (DLIR) in improving image quality and reducing beam-hardening artifacts of low-dose abdominal CT. 【Methods】 For this study we prospectively enrolled 26 patients (14 males and 12 females, mean age of 60.35±10.89 years old) who underwent CT urography between October 2019 and June 2020. All the patients underwent conventional-dose unenhanced CT and contrast-enhanced CT in the portal venous phase (noise index of 10; volume computed tomographic dose index: 9.61 mGy) and low-dose CT in the excretory phase(noise index of 23; volume computed tomographic dose index: 2.95 mGy). CT images in the excretory phase were reconstructed using four algorithms: ASiR-V 50%, DLIR-L, DLIR-M, and DLIR-H. Repeated measures ANOVA and Kruskal-Wallis H test were used to compare the quantitative (skewness, noise, SNR, CNR) and qualitative (image quality, noise, beam-hardening artifacts) values among the four image groups. Post hoc comparisons were performed using Bonferroni test. 【Results】 In either quantitative or qualitative evaluation, the SNR, CNR, overall image quality score, and noise of DLIR images were similar or better than ASiR-V 50%. In addition, the SNR, CNR, and overall image quality scores increased as the DLIR weight increased, while the noise decreased. There was no statistically significant difference in the distortion artifacts (P=0.776) and contrast-induced beam-hardening artifacts (P=0.881) scores among these groups. 【Conclusion】 Compared with the ASiR-V 50% algorithm, DLIR algorithm, especially DLIR-M and DLIR-H, can significantly improve the image quality of low-dose abdominal CT, but has limitations in reducing contrast-induced beam-hardening artifacts.
8.Technical specification for orthodontic transmission straight wire technique
Jiuxiang LIN ; Lili CHEN ; Bing HAN ; Si CHEN ; Weiran LI ; Zuolin JIN ; Bing FANG ; Yuxing BAI ; Lin WANG ; Jun WANG ; Hong HE ; Yuehua LIU ; Min HU ; Jinlin SONG ; Yang CAO ; Yannan SUN ; Xiaomo LIU ; Jieni ZHANG ; Yunfan ZHANG
Chinese Journal of Stomatology 2023;58(12):1217-1226
Malocclusion is an oral disease with a high prevalence. The goal of orthodontic treatment is health, aesthetics, function and stability. The transmission straight wire appliance and technique is an innovative orthodontic system with independent intellectual property rights invented by Professor Jiuxiang Lin′s team based on decades of clinical experience, which provides a new solution for the non-surgical correction of skeletal malocclusions, especially class Ⅲ malocclusion, and it is also a good carrier for the implementation of the concept of healthy orthodontics. Due to the lack of guidelines, how to implement standardized application of transmission straight wire technique remains a problem to be solved. This technical specification was formed by combining the guidance from Professor Jiuxiang Lin and joint revision by a number of authoritative experts from the Orthodontic Special Committee, Chinese Stomatological Association, with reference to relevant literatures, and combined with abundant clinical experience of many experts. This specification aims to provide reference to standardize the clinical application of transmission straight wire technique, so as to reduce the risk and complications, and finally to improve the clinical application level of this technique.
9.The effect of CT reconstruction kernels and display window settings on the detection and measurement of pulmonary solid nodules
Yannan CHENG ; Xianjun LI ; Xinyu LI ; Jianying LI ; Le CAO ; Jingtao SUN ; Jian YANG ; Jianxin GUO
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(3):476-482
【Objective】 To assess the effect of reconstruction kernels and window settings on the detection and measurement of pulmonary solid nodules and their measurement variability and repeatability. 【Methods】 We retrospectively recruited 49 patients with pulmonary solid nodules who had undergone low-dose CT scanning. Images were reconstructed using five reconstruction kernels: lung, bone, chest, detail and standard kernels. Two radiologists independently assessed the detection rate, diameter and CT number measurement of nodules under the five kernels and two window settings (lung-window and mediastinal-window). Bland-Altman plots and relative average deviation (RAD) were used to evaluate the repeatability and variability of nodule diameter and CT number measurement. 【Results】 Seventy-seven nodules were detected on lung-window regardless of reconstruction kernels, while the detection rates (75.3%-98.7%) were significantly different (P<0.001) on the mediastinal-window, with the lung kernel significantly improving the detection of nodules with the diameter below 6 mm. In both display windows, the diameter and CT number measurements among reconstruction kernels were similar except for the lung kernel. The lung-window had better variability in the diameter measurement while mediastinal-window was better in CT number measurement among various reconstruction kernels. Although the variability in the diameter of the nodule on the lung-window and mediastinal-window was similar, there was a significant difference in the variability in the diameter measurement among different reconstruction kernels on the mediastinal-window (P=0.004). No significant difference in the variability in the CT number measurement was found among the different reconstruction kernels (lung-window P=0.163; mediastinal-window P=0.201), and the variability in the CT number measurements on the mediastinal-window was smaller than that of the lung-window. Both window displays had acceptable repeatability in diameter and CT number measurement; however, the mediastinal-window was better in CT number measurement. 【Conclusion】 The lung kernel can improve the detection of pulmonary solid nodules below 6 mm, but is limited in the CT number measurement. The lung-window display provides better variability in measuring nodule diameter, while mediastinal-window display is better at measuring CT numbers.
10.Research progress of long non-coding RNA in medical parasitology
Yannan GAO ; Su HAN ; Xinyi HU ; Shanshan DUAN ; Beibei SUN ; Weizhe ZHANG ; Xiaoli ZHANG
Chinese Journal of Endemiology 2021;40(2):160-163
Long non-coding RNA (lncRNA) is defined as non-protein coding transcript longer than 200 nucleotides. In the form of RNA, it affects gene expression at the epigenetic, transcriptional and post-transcriptional levels, and is widely involved in the body's pathophysiological processes. This review summarizes the research progress of lncRNA in the field of parasitology in order to find new targets for the prevention and treatment of parasitic diseases.

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