Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.

Objective:To investigate the clinical and pathological characteristics of primary thoracic synovial sarcoma (PTSS).Methods:Forty-two PTSS cases diagnosed at the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from October 2011 to April 2024 were analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. Their clinicopathological features were also reviewed. SS18 rearrangement was assessed in 28 cases using fluorescence in situ hybridization (FISH). Next generation sequencing (NGS) was performed on 8 cases.Results:Among the 42 cases, there were 23 biopsies and 19 surgically-removed specimens. One case was a specimen resected after neoadjuvant chemotherapy. There were 22 males and 20 females, with an age ranging from 6 to 68 years. Twenty-nine cases occured in the lung, 6 in mediastinum, 4 in pericardium, 1 in visceral pleura, and 1 in right atrium. One case did not show any unequivocal primary site. Computed tomography showed the tumors were manifested as a cystic mass, a solid mass, or thickening of the pleura and pericardium. Thirty-two cases had respiratory symptoms, while 19 had pleural effusion. One case had a history of radiotherapy for papillary thyroid carcinoma. Nineteen patients were treated with surgery, while 19 were treated with chemotherapy without surgery. Four patients were diagnosed and discharged, without specific treatment on the record. Morphologically, 1 case was biphasic type, 39 cases were monophasic type, and 2 cases were poorly differentiated type. In addition to the typical morphology of synovial sarcoma, tumors also showed pulmonary bullous changes, stromal collagen hyalinization, hemangiopericytoma-like vasculature, stromal edematous myxoid changes, and microcystic structure. Immunohistochemically, all cases were diffusely positive for TRPS1 (22/22), TLE1 (21/22), CD99 (26/26), SS18-SSX (25/25) and INI1 (12/12), including 3 cases with decreased expression of INI1. Twenty-one cases were focally positive for EMA (21/30), 4 cases for SMA (4/23), 2 cases for S-100 (2/28), and 2 cases (2/35) for CKpan. Twenty-eight cases (28/28) had SS18 rearrangement displaying a split signal on FISH analysis. Eight cases were found to have mutations in SMC1A, NOTCH2, CDK12, SPRY4, BRCA1, STK11, NF2, and PDGFRα genes using NGS. Eighteen of the 29 patients survived and 16 showed disease progression.Conclusions:PTSS is more commonly found in the lungs than other sites and has non-classical morphological features of various types, which need to be differentiated from other tumors. TRPS1 is highly expressed in PTSS and has certain diagnostic values. The diagnosis of PTSS also requires combination of patient′s medical history with thorough imaging studies.

Objective To investigate the expression changes of iron autophagy-mitochondrial ferric ion transport protein families(SFXNs)in acute kidney injury(AKI)and chronic kidney disease(CKD)mouse models induced by cisplatin(Cis)and ischemia reperfusion(IR).Methods C57BL/6 mice were randomly divided into control group(control),Cis-AKI group,Cis-CKD group,sham-operated group(sham),IR-AKI group,and IR-CKD group.Serum and kidney tissue samples were collected from mice.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels were detected.Pathological changes in renal tissues were observed by HE staining.Western blot was used to detect the expression of renal SFXNs and kidney injury related proteins.Results Compared with the control or sham group,the levels of BUN and Cr in the serum of the model group were significantly increased(P＜0.05),the renal tissue showed significant pathological damage,with the kidney injury molecule-1(KIM-1),neutrophil gelatinase-associated lipocalin(NGAL),and pro-apoptotic protein Bax significantly upregulated(P＜0.05),while the anti-apoptotic protein Bcl-2 was significantly downregulated(P＜0.05).Compared to the control or sham group,the Cis-AKI group showed a significant downregulation of SFXN4(P＜0.05);The SFXN4 and SFXN5 subtypes were significantly downregulated in the IR-AKI group and Cis-CKD group(P＜0.05);All five subtypes of SFXN in the IR-CKD group were significantly downregulated(P＜0.05).Conclusions Cis or IR in-duces renal tissue damage and tubular mitochondrial injury in mice and affects the expression of SFXN family pro-teins,suggesting their potential role in renal injury of animal models.

Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.

Objective:To investigate the clinical and pathological characteristics of primary thoracic synovial sarcoma (PTSS).Methods:Forty-two PTSS cases diagnosed at the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from October 2011 to April 2024 were analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. Their clinicopathological features were also reviewed. SS18 rearrangement was assessed in 28 cases using fluorescence in situ hybridization (FISH). Next generation sequencing (NGS) was performed on 8 cases.Results:Among the 42 cases, there were 23 biopsies and 19 surgically-removed specimens. One case was a specimen resected after neoadjuvant chemotherapy. There were 22 males and 20 females, with an age ranging from 6 to 68 years. Twenty-nine cases occured in the lung, 6 in mediastinum, 4 in pericardium, 1 in visceral pleura, and 1 in right atrium. One case did not show any unequivocal primary site. Computed tomography showed the tumors were manifested as a cystic mass, a solid mass, or thickening of the pleura and pericardium. Thirty-two cases had respiratory symptoms, while 19 had pleural effusion. One case had a history of radiotherapy for papillary thyroid carcinoma. Nineteen patients were treated with surgery, while 19 were treated with chemotherapy without surgery. Four patients were diagnosed and discharged, without specific treatment on the record. Morphologically, 1 case was biphasic type, 39 cases were monophasic type, and 2 cases were poorly differentiated type. In addition to the typical morphology of synovial sarcoma, tumors also showed pulmonary bullous changes, stromal collagen hyalinization, hemangiopericytoma-like vasculature, stromal edematous myxoid changes, and microcystic structure. Immunohistochemically, all cases were diffusely positive for TRPS1 (22/22), TLE1 (21/22), CD99 (26/26), SS18-SSX (25/25) and INI1 (12/12), including 3 cases with decreased expression of INI1. Twenty-one cases were focally positive for EMA (21/30), 4 cases for SMA (4/23), 2 cases for S-100 (2/28), and 2 cases (2/35) for CKpan. Twenty-eight cases (28/28) had SS18 rearrangement displaying a split signal on FISH analysis. Eight cases were found to have mutations in SMC1A, NOTCH2, CDK12, SPRY4, BRCA1, STK11, NF2, and PDGFRα genes using NGS. Eighteen of the 29 patients survived and 16 showed disease progression.Conclusions:PTSS is more commonly found in the lungs than other sites and has non-classical morphological features of various types, which need to be differentiated from other tumors. TRPS1 is highly expressed in PTSS and has certain diagnostic values. The diagnosis of PTSS also requires combination of patient′s medical history with thorough imaging studies.

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Objective:To screen the endoplasmic reticulum stress (ERS) signature-related differentially expressed genes (DEG) in gastric cancer and to construct a prognostic risk model based on a bioinformatics.Methods:Transcriptome sequencing data (RNA-seq) of 375 gastric cancer and 32 paracancerous tissue samples downloaded from The Cancer Genome Atlas (TCGA) database and the corresponding clinical information were obtained as training set samples; data of 387 gastric cancer patients (GSE84437) from Gene Expression Omnibus (GEO) database were downloaded as validation set samples. All data were obtained on December 25, 2021. A total of 785 ERS signature-related genes (ERS-RG) were obtained from the GeneCards database. DEG between gastric cancer tissues and paracancerous tissues in the TCGA database was analyzed. The identified gastric cancer DEG were intersected with ERS-RG from the GeneCards database to obtain gastric cancer ERS signature-related DEG, which were analyzed for gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Univariate Cox proportional risk model was used to screen ERS signature-related DEG with prognostic value in gastric cancer, and LASSO regression analysis was performed to construct a polygenic prognostic risk model, and to calculate the prognostic risk score. The patients in training set and validation set were divided into high-risk group and low-risk group according to the median of the prognostic risk score (2.369); Kaplan-Meier survival analysis was used to compare the overall survival (OS) and to draw time-dependent receiver operating characteristic (ROC) curves of patients in the two groups; nomogram was drawn based on the prognostic independent influencing factors of gastric cancer. The characteristic immune cell infiltration abundance between the two groups was analyzed by using the inverse convolution-based CIBERSORT algorithm. Cytolytic activity scores were calculated by using the geometric mean of granzyme A and perforin 1 expression. According to the median prognostic risk score (2.369) and median tumor mutation burden (TMB) (3.000), all patients with gastric cancer were divided into high risk score-high TMB group, high risk score-low TMB group, low risk score-high TMB group and low risk score-low TMB group to compare the OS of patients in each group.Results:A total of 444 ERS signature-related DEG in gastric cancer including 168 down-regulated genes and 276 up-regulated genes were obtained, which were mainly enriched in biological processes such as protein processing in the endoplasmic reticulum, extracellular matrix (ECM) receptor interactions and unfolded protein responses (all P < 0.05). Univariate Cox regression analysis showed that 12 prognostic-related ERS signature-related DEG in gastric cancer were screened out. LASSO regression analysis was performed to obtain a prognostic risk score = 0.052×NOS3+0.137×PON1+0.067×CXCR4+0.131×MATN3+0.116×ANXA5+0.090×SERPINE1. The results of Kaplan-Meier analysis showed that the OS of the low-risk group in both the training and validation sets was better than that of the high-risk group (all P < 0.01). The results of the time-dependent ROC curve analysis showed that the AUC for the 3-year, 5-year, 8-year OS rates was 0.695, 0.786, 0.698, respectively in the training set, while the AUC for the 3-year 5-year, 8-year OS rates was 0.580, 0.625, 0.627, respectively in the validation set. Multivariate Cox regression analysis showed that prognostic risk score ( HR = 3.598, 95% CI 2.290-5.655, P < 0.001) and tumor stage ( HR = 1.344, 95% CI 1.057-1.709, P < 0.05) were independent factors influencing the prognosis of gastric cancer. Among 375 gastric cancer patients in the TCGA database, the expression levels of ATF6, HSPA5, XBP1 and ATF4 in the high-risk group were higher than those in the low-risk group (all P < 0.05); CIBERSORT results showed that the abundance of activated CD4 memory T cells in the high-risk group was lower than that in the low-risk group, and the abundance of both M0 and M2 macrophages in the high-risk group was higher than that in the low-risk group (all P < 0.05). The expression levels of common immune checkpoints (CD274, CTLA4, TNFRSF9, TIGIT, PDCD1, LAG3) in the high-risk group were all higher than those in the low-risk group (all P < 0.05). Cytolytic activity score in the high-risk group was higher than that in the low-risk group ( P < 0.05). The prognostic risk score was negatively correlated with TMB ( r = -0.20, P < 0.001). Patients in the low-risk score-high TMB group had the best OS and those in the high-risk score-low TMB group had the worst OS (both P < 0.001). Conclusions:The prognostic risk score model is established based on 6 ERS signature-related DEG in gastric cancer and its prognostic risk score may be effective as an independent prognostic factor to predict the prognosis of gastric cancer patients.

Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To investigate the significance of multicolor flow cytometry (MFC) monitoring of minimal residual disease (MRD) in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CD19-chimeric antigen receptor(CAR)-T cell immunotherapy for patients with refractory, relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL).Methods:37 patients with r/r B-ALL admitted to Hebei Yanda Lu Daopei Hospital from January to July 2019, aged 15 (6, 19) years old, including 24 males and 13 females, were treated with CD19-CAR-T cell immunotherapy bridging allo-HSCT. MFC with cytoplasmic CD79a antibody to set up B-cell gates was used to monitor patients′ bone marrow (BM), cerebrospinal fluid (CSF), and tissue samples on day 0 (prior to the CAR-T cell immunotherapy), day 15, day 28 post CAR-T cell immunotherapy, and post transplantation.The MRD values of these samples were analyzed to evaluate the residual tumor cells and metastasis. The killing effect of the CAR-T cells was evaluated by the recovery of CD19+B cells before transplantation and the period between the timepoint when CD19+B cells was recovered and the timepoint when CAR-T cells were infused. Peripheral blood CAR-T cells were counted at different time points. Statistic analysis was performed by Kaplan-Meie assay and Log-rank test to analyze the difference of univariate cumulative survival.Results:(1)Among the 37 patients, 8 died and 29 survived. 5 patients relapsed after transplantation, of which 4 relapsed patients died and 1 survived. (2)MFC MRD negative remission rate of the death group was lower than that of the survival group at the following time points: post-CAR-T therapy and prior to transplantation (5/8 vs. 28/29, χ 2=7.540, P=0.006); day 15 of the CAR-T cell reinfusion (3/8 vs. 24/29, χ 2=6.512, P=0.011); day 28 of the reinfusion (3/8 vs. 276/29, χ 2=10.065, P=0.002). The probability of extramedullary MFC MRD positive tumor infiltration in the death group was higher than that in the survival group(7/8 vs. 14/29, χ 2=3.931, P=0.047). After CAR-T cell immunotherapy, the recovery period of CD19-positive cells in the death group, or the time for CAR-T cells to kill CD19-positive cells, was shorter than that in the survival group [42.00 days(30.00,49.00) vs. 55.00 days(41.50,73.50), Z=0.022, P=0.020]. Conclusion:The positive results of MRD by MFC at the following timepoints may predict unfavorable outcomes, such as post-CAR-T therapy and prior to transplantation, day 15 and 28 of the CAR-T cell immunotherapy, which may provide some guidance for clinical management.