1.Current Status,Strategies and Prospects of Traditional Chinese Medicine Diagnosis and Treatment for Irritable Bowel Syndrome
Yandong WEN ; Zhi YANG ; Shaogang HUANG ; Zhongyu LI ; Xiangxue MA ; Qing XU ; Liqing DU ; Bochao YUAN ; Yibing TIAN ; Wentong GE ; Xiaofan ZHAO ; Chang LIU ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(4):404-409
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized primarily by abdominal pain and altered defecation habits. In recent years, traditional Chinese medicine (TCM) has made progress in multiple aspects of IBS research and treatment, including syndrome distribution, development of TCM formulas, clinical efficacy evaluation, external therapies, and psychosocial regulation. However, it still faces challenges such as over-reliance on symptomatic manifestations rather than biomarkers for diagnostic criteria, and the lack of high-quality evidence-based data supporting the efficacy of TCM formulas in treating IBS. This paper proposed that TCM diagnosis and treatment of IBS should adhere to the strategy of integrating the holistic concept with syndrome differentiation and treatment, combining TCM external therapies such as acupuncture, moxibustion and acupoint application), and emphasizing individualized diagnosis and treatment for psychosomatic abnormalities. Future research should integrate multi-omics technologies, artificial intelligence and other methods to deepen the understanding of the pathogenesis of IBS and the mechanisms of TCM formulas, so as to promote the standardization and internationalization of TCM in the diagnosis and treatment of IBS.
2.Study on the capture of Helicobacter pylori released from Candida using immunomagnetic bead
Tingting LUO ; Jianchao SUN ; Tingxiu YANG ; Xiaoli XU ; Guzhen CUI ; Qing LUO ; Shuwei ZHUO ; Qi LIU ; Zhenghong CHEN
Acta Universitatis Medicinalis Anhui 2026;61(3):402-408
ObjectiveTo investigate the ability of clinically isolated, Helicobacter pylori (H. pylori)-specific gene polymerase chain reaction (PCR)-positive gastric, vaginal, and fecal Candida to release H. pylori. MethodsResuscitate 4 strains of H. pylori -specific 16S rDNA and ureA gene PCR-positive Candida strains isolated in laboratory from clinical sources, including 1 strain of gastric Candida, 1 strain of fecal Candida, 2 strains of vaginal Candida and the standard Candida albicans strain ATCC10231 (Ca10231). The presence of H. pylori-specific ureA in the 5 strains of Candida isolates was confirmed by PCR. The aforementioned strains of Candida and H.pylori were inoculated into urea medium and cultured in a constant temperature incubator at 37 ℃. The color change of the medium was observed daily. A change in the medium's color from yellow to red indicated the presence of urease activity. Then, the five strains of Candida and H. pylori were co-incubated with the magnetic beads coated with H. pylori antibodies respectively. Scanning electron microscopy (SEM) was employed to observe the presence of bacilli adsorbed on the surface of the magnetic beads. PCR was used to detect the presence of H.pylori-specific 16S rDNA and ureA genes on magnetic beads. ResultsThe PCR analysis of the ureA gene in the four Candida isolates was positive, whereas the Ca10231 strain tested negative. Upon culturing the four Candida isolates on urea medium, the medium color changed from yellow to red which was determined to be urease positive, while the medium containing Ca10231 remained unchanged, which was urease negative. SEM revealed that bacilli could be observed on the surface of magnetic beads co-incubated with the 4 strains of Candida of clinical origin and H.pylori isolate. Specifically, PCR testing of the magnetic beads co-incubated with one vaginal Candida, one gastric Candida and H.pylori isolate showed positive results for the 16S rDNA and ureA genes of H. pylori; however, the PCR tests for the two genes were negative for the magnetic beads co-incubated with the other two Candida isolate. ConclusionThis study demonstrates that H. pylori-specific genes Candida can release H. pylori.
3.Lipidomics Combined with Machine Learning for Screening Biomarkers of Early-Stage Lung Cancer in the Elderly
Qing WANG ; Yue HE ; Xu LIU ; Zifan LI ; Kezhong CHEN
Medical Journal of Peking Union Medical College Hospital 2026;17(3):652-662
Based on plasma lipidomics combined with machine learning approaches, this study aimed to screen molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients and to evaluate their diagnostic performance. This was a retrospective diagnostic study consisting of two parts. The first part involved molecular biomarker screening. Elderly patients with early-stage lung cancer (early lung cancer group), patients with benign pulmonary nodules (benign nodule group), and contemporaneous healthy individuals undergoing physical examinations (healthy control group) were enrolled from Peking University People's Hospital between November 2023 and November 2024. In addition, early-stage lung cancer patients and healthy controls meeting the inclusion criteria from a previous study of our research group were included as an independent validation cohort. Plasma samples were collected from all subjects, and untargeted lipidomics analysis was performed using high-performance liquid chromatography-mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate metabolic differences between groups. L1-regularized support vector machine combined with incremental feature selection was employed to screen diagnostic biomarkers for early-stage lung cancer. Model performance was assessed using receiver operating characteristic curves, calibration curves, Brier scores, and decision curve analysis. The second part involved functional validation of the molecular biomarkers using the human lung adenocarcinoma cell line A549, with palmitoylcarnitine (CAR 16∶0) selected as a representative biomarker for functional validation via CCK-8 and cell scratch assays. A total of 36 patients in the early lung cancer group, 35 patients in the benign nodule group, and 41 healthy controls were enrolled, along with an independent validation cohort of 110 individuals (59 patients with early-stage lung cancer and 51 healthy controls). The principal component analysis results demonstrated that quality control samples were tightly aggregated at the centroid of all samples, reflecting robust instrument performance and dependable data quality.Orthogonal partial least squares discriminant analysis revealed significant metabolic differences between the early lung cancer group and the control group (benign nodule group + healthy control group) (R2X=0.406, R2Y=0.529, Q2Y=0.44). L1-regularized support vector machine identified five carnitine-related lipids-palmitoleoylcarnitine(CAR 16∶1), palmitoylcarnitine, The five plasma carnitine-related lipids screened based on untargeted lipidomics and machine learning may serve as potential molecular biomarkers for the diagnosis of early-stage lung cancer in elderly patients. The high-sensitivity characteristic of the model makes it particularly suitable for screening scenarios in early-stage lung cancer.
4.Effect of Different Degrees of Blood Stasis on Cognitive Function and Plasma Differential Metabolites in Patients with Coronary Heart Disease
Shihan XU ; Yanfei LIU ; Fenglan LIU ; Qing WANG ; Fengqin XU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):167-176
ObjectiveTo explore the correlation between the blood stasis score of coronary heart disease(CAD) and mild cognitive impairment(MCI), as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI(CADMCI) through a cross-sectional study, and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients. MethodsAccording to the diagnostic criteria of CAD and CAD blood stasis, patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included. According to the Montreal Cognitive Assessment(MoCA) scale score, the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group. The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model. The receiver operating characteristic(ROC) curve was drawn, and the area under the curve(AUC) was calculated to evaluate the sensitivity and specificity of the model. According to the blood stasis score, the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detect plasma metabolites in each group of patients. The differential metabolites were screened according to variable importance in the projection(VIP) value≥1, fold change(FC)<0.67 or >1.5, and P<0.05. ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples. ResultsA total of 266 CAD patients were included in this study. Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI[odds ratio(OR)=1.619, 95% confidence interval(CI) 1.223-2.142, P<0.001, ROC curve AUC was 0.615(95% CI 0.547-0.683, P=0.001)], indicating that the CAD blood stasis score has a certain predictive value for MCI. Plasma non-targeted metabolomics analysis showed that the main differential metabolites between CAD blood stasis and CADMCI blood stasis were lipid metabolites, among which phosphatidylcholine[20∶4(5Z, 8Z, 11Z, 14Z)/P-18∶1(11Z)] had the best discriminatory efficiency(ROC curve AUC=0.867, 95% CI 0.754-0.942). Further analysis of the differential metabolites between mild and severe blood stasis showed that lipid metabolites were also the main differential metabolites between mild and severe blood stasis. Among them, 1α,25-dihydroxy-2β-(2-hydroxyethoxy) vitamin D3 had the best efficacy in distinguishing mild and severe CAD blood stasis(AUC=0.813, 95% CI 0.649-0.951), and phosphatidylcholine 34∶2 had the best efficacy in distinguishing mild and severe CADMCI blood stasis(AUC=0.819, 95% CI 0.640-0.941). ConclusionThere is a significant correlation between CAD blood stasis score and MCI. Phosphatidylcholine metabolites play an important role in the pathogenesis of CADMCI blood stasis and severe blood stasis. The CAD blood stasis score combined with the detection of phosphatidylcholine metabolites can provide a reference for the development of early and efficient identification strategies for CADMCI.
5.Standardization of outpatient medical record in rehabilitation setting
Ye LIU ; Qing QIN ; Haiyan YE ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):45-54
ObjectiveTo analyze the data structure and standards of rehabilitation outpatient medical records, to provide data support for improving the quality of rehabilitation outpatient care and developing medical insurance payment policies. MethodsBased on the normative documents issued by the National Health Commission, Basic Standards for Medical Record Writing and Standards for Electronic Medical Record Sharing Documents, in accordance with the Quality Management Regulations for Outpatient (Emergency) Diagnosis and Treatment Information Pages (Trial), reference to the framework of the World Health Organization Family of International Classifications (WHO-FICs), the data framework and content of rehabilitation outpatient medical records were determined, and the data standards were discussed. ResultsThis study constructed a data framework for rehabilitation outpatient medical records, including four main components: patient basic information, visit process information, diagnosis and treatment information, and cost information. Three major reference classifications of WHO-FICs, International Classification of Diseases, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions,were used to establish diagnostic standards and standardized terminology, as well as coding disease diagnosis, functional description, functional assessment, and rehabilitation interventions, to improve the quality of data reporting, and level of quality control in rehabilitation. ConclusionThe structuring and standardization of rehabilitation outpatient medical records are the foundation for sharing of rehabilitation data. The using of the three major classifications of WHO-FICs is valuable for the terminology and coding of disease diagnosis, functional description and assessment, and intervention in rehabilitation outpatient medical records, which is significant for sharing and interconnectivity of rehabilitation outpatient data, as well as for optimizing the quality and safety of rehabilitation medical services.
6.Structure, content and data standardization of inpatient rehabilitation medical record summary sheet
Haiyan YE ; Qing QIN ; Ye LIU ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):55-66
ObjectiveTo explore the standardization of inpatient rehabilitation medical record summary sheet, encompassing its structure, content and data standards, to enhance the standardization level of inpatient rehabilitation medical record summary sheet, improve data reporting quality, and provide accurate data support for medical insurance payment, hospital performance evaluation, and rehabilitation discipline evaluation. MethodsBased on the relevant specifications of the National Health Commission's Basic Norms for Medical Record Writing, Specifications for Sharing Documents of Electronic Medical Records, and Quality Management and Control Indicators for Inpatient Medical Record Summary Sheet (2016 Edition), this study analyzed the structure and content of the inpatient rehabilitation medical record summary sheet. The study systematically applied the three major reference classifications of the World Health Organization Family of International Classifications, International Classification of Diseases (ICD-10/ICD-11, ICD-9-CM-3), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), for disease diagnosis, functional description and assessment, and rehabilitation intervention, forming a standardized terminology system and coding methods. ResultsThe inpatient rehabilitation medical record summary sheet covered four major sections: inpatient information, hospitalization information, diagnosis and treatment information, and cost information. ICD-10/ICD-11 were the standards and coding tools for admission and discharge diagnoses in the inpatient rehabilitation medical record summary sheet. The three functional assessment tools recommended by ICD-11, the 36-item version of World Health Organization Disability Assessment Schedule 2.0, Brief Model Disability Survey and Generic Functioning domains, as well as ICF, were used for rehabilitation functioning assessment and the coding of outcomes. ICHI Beta-3 and ICD-9-CM-3 were used for coding surgical procedures and operations in the medical record summary sheet, and also for coding rehabilitation intervention items. ConclusionThe inpatient rehabilitation medical record summary sheet is a summary of the relevant content of the rehabilitation medical record and a tool for reporting inpatient rehabilitation data. It needs to be refined and optimized according to the characteristics of rehabilitation, with necessary data supplemented. The application of ICD-11/ICD-10, ICF and ICHI Beta-3/ICD-9-CM-3 classification standards would comprehensively promote the accuracy of inpatient diagnosis of diseases and functions. Based on ICD-11 and ICF, relevant functional assessment result data would be added, and ICHI Beta-3/ICD-9-CM-3 should be used to code rehabilitation interventions. Improving the quality of rehabilitation medical records and inpatient rehabilitation medical record summary sheet is an important part of rehabilitation quality control, and also lays an evidence-based data foundation for the analysis and application of inpatient rehabilitation medical record summary sheet.
7.Ginkgolide B inhibits cell proliferation and promotes cell apoptosis of MH7A human fibroblast-like synoviocytes through PI3K/AKT pathway
Linchen LIU ; Xiaoyan XU ; Chunmeng WEI ; Jirong YU ; Qing SHI ; Junjun SUN ; Dandan PANG ; Feiran WEI ; Xing LIU
Journal of China Pharmaceutical University 2025;56(2):216-224
To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.
8.Association between sleep fragmentation and body composition/blood pressure among 12-15 year old female students in Nanyang City
WANG Qing, SHI Bingqin, XU Guochang, LIU Rongzhi, HUANG Hua
Chinese Journal of School Health 2025;46(7):1027-1031
Objective:
To investigate the correlation between sleep fragmentation and body composition/blood pressure in female students of middle school, so as to provide theoretical guidance for preventing health risks associated with sleep fragmentation.
Methods:
From September 2022 to December 2023, 505 female students aged 12-15 years in Nanyang City were selected through stratified cluster random sampling and conducted Pittsburgh Sleep Quality Index(PSQI) survey. Participants were divided into Q 1- Q 4 groups based on sleep fragmentation index (SFI) quartiles. Body composition and blood pressure measurements were measured by adopting body composition analyzer and traditional mercury sphygmomanometer, and data were analyzed using χ 2 tests and linear regression.
Results:
Significant intergroup differences for Q 1- Q 4 were observed with increasing SFI levels for body mass index(BMI), fat percentage, muscle mass, bone mass, trunk fat percentage, systolic blood pressure, diastolic blood pressure, and PSQI total scores ( F =15.25,7.33,8.38,5.97,11.24,16.85,6.87,15.73, all P <0.05). SFI showed positive correlations with BMI, fat percentage, trunk fat percentage, and blood pressure( β =0.37,0.45,0.34,0.42,0.38), but negative correlations with muscle mass and bone mass( β =-0.35,-0.48) (all P <0.05). The χ 2 trend test revealed a significant increase in hypertension detection rates with elevated SFI ( χ 2=42.75, P <0.05). The χ 2 testing demonstrated statistically significant differences in hypertension incidence among different quartiles groups ( χ 2=14.16, P <0.05). After adjusting the significance level, hypertension incidence differences remained significant between Q 1and Q 4 ( χ 2=10.77), Q 2 and Q 4 groups ( χ 2=6.28) (both P <0.008 3).
Conclusions
Sleep fragmentation correlates significantly with body composition and blood pressure indicators in female students of middle school. Implementing sleep fragmentation interventions is essential for safeguarding female students health in middle school.
9.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
10.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.


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