1.Downregulation of LINC00638 contributes to the pathogenesis of rheumatoid arthritis-associated interstitial lung disease via inhibiting the Nrf2/ARE signaling pathway
Zhuojun LIAO ; Naiwang TANG ; Jiahui CHEN ; Xueying SUN ; Jiamin LU ; Qin WU ; Ronghuan YU ; Ying ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):421-431
Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n=3), RA patients without lung involvement (n=3), and healthy controls (n=3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.
2.18 F-FDG PET/MRI manifestations of gray matter heterotopia related to epilepsy
Yingxin LI ; Xueying LING ; Yongjin TANG ; Yong CHENG ; Hao XU
Chinese Journal of Medical Imaging Technology 2024;40(2):203-207
Objective To observe18F-FDG PET/MRI manifestations of gray matter heterotopia(GMH)related epilepsy.Methods Data of 27 patients with GMH and epilepsy diagnosed with MRI were retrospectively analyzed.Brain 18 F-FDG PET/MRI manifestations and complicated brain malformations were observed,and the classification of GMH were performed.Results Among 27 cases,periventricular GMH,focal subcortical GMH,subcortical lamellar(band)GMH and mixed GMH were detected each in 15,2,2 and 8 cases,respectively.Compared with cerebral white matter around the lesion or in the contralateral mirror area of the lesion,glucose hypermetabolism and glucose hypometabolism were found in 22 and 3 cases,respectively,while glucose metabolism was normal in 2 cases.Compared with gray matter in precentral gyrus,glucose hypermetabolism and glucose hypometabolism were observed in 8 and 16 cases,respectively,while glucose metabolism was normal in 3 cases.Six cases complicated with cerebral fissure deformity,6 cases with bilateral cerebellar hemispheric volume reduction,1 case with absence of pellucid septum and lower fornix,1 case with dysplasia of corpus callosum and 1 case with polymicrogyria.Conclusion 18 F-FDG PET/MRI manifestations of GMH related epilepsy had certain characteristics,which were helpful for clinical diagnosis.
3.Value of brain 18F-FDG PET/CT in the preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI
Chunyuan ZENG ; Hailing ZHOU ; Zhiqiang TAN ; Guixian TANG ; Huanhua WU ; Biao WU ; Yongjin TANG ; Xueying LING ; Qiang GUO ; Hao XU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(4):196-201
Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.
4.Associations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index:A family-based study
Huangda GUO ; Hexiang PENG ; Siyue WANG ; Tianjiao HOU ; Yixin LI ; Hanyu ZHANG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Xun TANG ; Jing LI ; Dafang CHEN ; Yonghua HU ; Tao WU
Journal of Peking University(Health Sciences) 2024;56(3):375-383
Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90%females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95%CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95%CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95%CI:0.004-0.076).The TyG index was 0.079(95%CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.
5.Sialic acid-mediated photochemotherapy enhances infiltration of CD8+ T cells from tumor-draining lymph nodes into tumors of immunosenescent mice.
Dezhi SUI ; Changzhi LI ; Xueying TANG ; Xianmin MENG ; Junqiang DING ; Qiongfen YANG ; Zhaowei QI ; Xinrong LIU ; Yihui DENG ; Yanzhi SONG
Acta Pharmaceutica Sinica B 2023;13(1):425-439
Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8+ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8+ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8+ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.
6.Radical therapy with or without chemotherapy in highly malignant non-metastatic prostate cancer: interim analysis of a prospective non-randomized controlled study
Mingwei MA ; Qi TANG ; Xianshu GAO ; Wei YU ; Hongzhen LI ; Mingxia SUN ; Kaiwei YANG ; Xiaoying LI ; Xin QI ; Jiayan CHEN ; Xueying REN
Chinese Journal of Radiation Oncology 2023;32(3):229-234
Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.
7.Atypical manifestations of acute coronary syndrome - throat discomfort: a multi-center observational study.
Yanqing FANG ; Xiaoting CHENG ; Wenhui PENG ; Xueying CHEN ; Chunping TANG ; Qiusheng HUANG ; Sihai WU ; Yibo HUANG ; Fanglu CHI ; Matthew R NAUNHEIM ; Huawei LI ; Bing CHEN ; Yilai SHU
Frontiers of Medicine 2022;16(4):651-658
To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients' main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2-31.5), 10.9 (95% CI 1.8-66.9), 25.4 (95% CI 3.6-179.9), and 81.2 (95% CI 13.0-506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
Acute Coronary Syndrome/etiology*
;
Dyspnea/etiology*
;
Humans
;
Pharyngitis/diagnosis*
;
Pharynx
;
Retrospective Studies
8.Noncontrast Computed Tomography-Based Radiomics Analysis in Discriminating Early Hematoma Expansion after Spontaneous Intracerebral Hemorrhage
Zuhua SONG ; Dajing GUO ; Zhuoyue TANG ; Huan LIU ; Xin LI ; Sha LUO ; Xueying YAO ; Wenlong SONG ; Junjie SONG ; Zhiming ZHOU
Korean Journal of Radiology 2021;22(3):415-424
Objective:
To determine whether noncontrast computed tomography (NCCT) models based on multivariable, radiomics features, and machine learning (ML) algorithms could further improve the discrimination of early hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (sICH).
Materials and Methods:
We retrospectively reviewed 261 patients with sICH who underwent initial NCCT within 6 hours of ictus and follow-up CT within 24 hours after initial NCCT, between April 2011 and March 2019. The clinical characteristics, imaging signs and radiomics features extracted from the initial NCCT images were used to construct models to discriminate early HE. A clinical-radiologic model was constructed using a multivariate logistic regression (LR) analysis. Radiomics models, a radiomics-radiologic model, and a combined model were constructed in the training cohort (n = 182) and independently verified in the validation cohort (n = 79). Receiver operating characteristic analysis and the area under the curve (AUC) were used to evaluate the discriminative power.
Results:
The AUC of the clinical-radiologic model for discriminating early HE was 0.766. The AUCs of the radiomics model for discriminating early HE built using the LR algorithm in the training and validation cohorts were 0.926 and 0.850, respectively.The AUCs of the radiomics-radiologic model in the training and validation cohorts were 0.946 and 0.867, respectively. The AUCs of the combined model in the training and validation cohorts were 0.960 and 0.867, respectively.
Conclusion
NCCT models based on multivariable, radiomics features and ML algorithm could improve the discrimination of early HE. The combined model was the best recommended model to identify sICH patients at risk of early HE.
9.Epidemiological characteristics of new pneumoconiosis in different industries in Tianjin
Qiang ZENG ; Lihong DENG ; Xiaolin LI ; Ya GAO ; Jing LIU ; Xueying YANG ; Huijing TANG ; Xin WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):118-122
Objective:To analyze the distribution characteristics of new pneumoconiosis in different industries in Tianjin from 2009 to 2018, in order to provide a theoretical basis for the prevention and treatment of pneumoconiosis.Methods:In November 2019, the data of new pneumoconiosis cases in Tianjin from 2009 to 2018 were collected and classified according to difference industries. The epidemiological characteristics of new pneumoconiosis in different industries were analyzed based on time, type of pneumoconiosis, type of work, age, and working age.Results:A total of 4657 new cases of pneumoconiosis were reported in Tianjin from 2009 to 2018, 4640 cases (99.63%) in the first stage, 13 cases (0.28%) in the second stage, and 4 case (0.09%) in the third stage. The number of new cases increased with time and then decreased. Among them, there were 3482 males (74.77%) and 1175 females (25.23%) . The proportion of women with new pneumoconiosis in the non-metallic mineral products industry was the highest, and the differences were statistically significant ( P<0.05) . There are differences in the distribution of new pneumoconiosis species in different industries (χ 2=4920.11, P<0.05) . Silicosis is mainly distributed in non-metallic mineral products industry, metal smelting and rolling processing industry, petroleum processing coking and nuclear fuel processing industries. Foundry worker′s pneumoconiosis is mainly distributed in the general equipment manufacturing industry and special equipment manufacturing industry, and cement pneumoconiosis is mainly distributed in the non-metallic mineral products industry. The types of work are mainly distributed in smelting, casting, raw materials and forming workers, and the sum of the three accounts for 36.46% (1689/4657) . The M ( P25, P75) of diagnosis age was 56.0 (50.0, 63.0) years, and the M ( P25, P75) of working age was 19.0 (16.0, 26.0) years. The working age of new pneumoconiosis patients in the petroleum processing, coking and nuclear fuel processing industries is 19.0 (16.0, 26.0) years, which is shorter than that of other industries ( P<0.05) ; The diagnostic age of the general equipment manufacturing industry is 54.0 (49.0, 59.0) years, which is less than that of other industries ( P<0.05) . New pneumoconiosis is mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in non-metallic mineral products industry, metal smelting, calendar processing industry and general equipment manufacturing industry are mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in the metal products industry, special equipment manufacturing industry and petroleum processing, coking and nuclear fuel processing industries are mainly distributed in large enterprises. Conclusion:The work of preventing and controlling pneumoconiosis in Tianjin has a long way to go. We should implement targeted measures according to the characteristics of pneumoconiosis industry, strengthen the supervision of hazard industries, and effectively control the occurrence of pneumoconiosis.
10.Epidemiological characteristics of new pneumoconiosis in different industries in Tianjin
Qiang ZENG ; Lihong DENG ; Xiaolin LI ; Ya GAO ; Jing LIU ; Xueying YANG ; Huijing TANG ; Xin WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):118-122
Objective:To analyze the distribution characteristics of new pneumoconiosis in different industries in Tianjin from 2009 to 2018, in order to provide a theoretical basis for the prevention and treatment of pneumoconiosis.Methods:In November 2019, the data of new pneumoconiosis cases in Tianjin from 2009 to 2018 were collected and classified according to difference industries. The epidemiological characteristics of new pneumoconiosis in different industries were analyzed based on time, type of pneumoconiosis, type of work, age, and working age.Results:A total of 4657 new cases of pneumoconiosis were reported in Tianjin from 2009 to 2018, 4640 cases (99.63%) in the first stage, 13 cases (0.28%) in the second stage, and 4 case (0.09%) in the third stage. The number of new cases increased with time and then decreased. Among them, there were 3482 males (74.77%) and 1175 females (25.23%) . The proportion of women with new pneumoconiosis in the non-metallic mineral products industry was the highest, and the differences were statistically significant ( P<0.05) . There are differences in the distribution of new pneumoconiosis species in different industries (χ 2=4920.11, P<0.05) . Silicosis is mainly distributed in non-metallic mineral products industry, metal smelting and rolling processing industry, petroleum processing coking and nuclear fuel processing industries. Foundry worker′s pneumoconiosis is mainly distributed in the general equipment manufacturing industry and special equipment manufacturing industry, and cement pneumoconiosis is mainly distributed in the non-metallic mineral products industry. The types of work are mainly distributed in smelting, casting, raw materials and forming workers, and the sum of the three accounts for 36.46% (1689/4657) . The M ( P25, P75) of diagnosis age was 56.0 (50.0, 63.0) years, and the M ( P25, P75) of working age was 19.0 (16.0, 26.0) years. The working age of new pneumoconiosis patients in the petroleum processing, coking and nuclear fuel processing industries is 19.0 (16.0, 26.0) years, which is shorter than that of other industries ( P<0.05) ; The diagnostic age of the general equipment manufacturing industry is 54.0 (49.0, 59.0) years, which is less than that of other industries ( P<0.05) . New pneumoconiosis is mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in non-metallic mineral products industry, metal smelting, calendar processing industry and general equipment manufacturing industry are mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in the metal products industry, special equipment manufacturing industry and petroleum processing, coking and nuclear fuel processing industries are mainly distributed in large enterprises. Conclusion:The work of preventing and controlling pneumoconiosis in Tianjin has a long way to go. We should implement targeted measures according to the characteristics of pneumoconiosis industry, strengthen the supervision of hazard industries, and effectively control the occurrence of pneumoconiosis.

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