Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective:To compare the prevalence and progression of subclinical atherosclerosis (SA) in populations with different cardiovascular disease (CVD) risks in China, and clarify the relationship between CVD risk stratification and SA.Methods:All participants were from Beijing Community-Based Cohort of Atherosclerosis. A total of 1 462 participants underwent carotid ultrasound and coronary computed tomography scan during 2008-2009 and 2013-2014. After excluding 191 participants with history of CVD and incomplete baseline data, 1 271 participants were included in final analysis. The 10-year CVD risk for participants were calculated based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) equation, and risk stratification was performed. The prevalence and progression of SA was determined by carotid intima-media thickness (cIMT), carotid plaque score and coronary artery calcification (CAC) score.Results:In the participants included in this study, 536 (42.2%), 418 (32.9%) and 317 (24.9%) were classified to have low, intermediate and high 10-year risk, respectively. With the rising level of 10-year risk, the proportion of patients with SA and SA progression increased. In low, intermediate and high CVD risk groups, the proportions of participants with CAC were 16.4%, 36.4% and 52.0% (trend P<0.001); and 15.4%, 36.4% and 53.6% had progression of CAC during follow-up, respectively (trend P<0.001); compared with low-risk group, RRs for CAC progression of intermediate and high-risk groups were 2.316 (95% CI: 1.714-3.129) and 3.322 (95% CI: 2.472-4.463), respectively (trend P<0.001). The trend of relationship between CVD risk stratification and cIMT and carotid plaque progression were consistent with CAC. Conclusions:This current study shows CVD risk stratification is closely related to the prevalence and progression of atherosclerosis in Chinese population. However, many people with low CVD risk have atherosclerotic change in their carotid and coronary artery.

Purpose Focusing on the characteristics of for-malin fixed paraffin embedded(FFPE)samples,explored nano-magnetic bead nucleic acid extraction solutions with higher qual-ity/yield and continued to improve molecular pathology technolo-gy.Methods Alternative magnetic beads were synthesised in four major categories and 15 sub-categories and we screened to obtain high-quality/yield magnetic beads centred on FFPE samples.Simulated conventional tissues,simulated coarse needle punctures(liver),and simulated fiberoptic bronchoscopy sam-ples(lungs)were sectioned with the same number of serial slices in tubes.The nucleic acids of slices were extracted using the best magnetic beads screened in this study and common com-mercially available kits,and then perform comparison and purifi-cation quality parameters such as total amount and fragment size.The downstream applications of nucleic acids were validated by PCR and Sanger sequencing.Results Screening all homemade nanomagnetic beads centered on the DNA of FFPE samples,the total recoveries of the best performance nanomagnetic beads were obtained to be 58.5％±1.58％,and the total recoveries of five commercially available commercial magnetic beads and three do-mestic kit magnetic beads ranged from 18.68％to 40.71％.The total amount of DNA(ng)extracted from the same amount of tis-sue(serial slices),the nucleic acid yield of this study in simu-lated conventional tissues,simulated coarse needle punctures,and simulated fiberoptic bronchoscopy samples were increased by 39.49％-181.72％compared with those of the commercially a-vailable kits(P＜0.05).The total amount of extracted nucleic acid from simulated fiberoptic bronchoscopy tissue sections can be more than 100 ng for 1 slice(4 μm)and more than 400 ng for 5 slices.Conclusion The DNA purification nanomagnetic beads screened with DNA from FFPE samples have a significant enhancement comparing to the existing commercial bead proto-cols,and provide space for quality assurance,automated testing,and program expansion for clinical molecular pathology testing.

Objective:To detect the expressions of S100P, mucin 5A, mucin 6, estrogen-inducing protein pS2, C-reactive protein (CRP), N-cadherin and CD56 in intrahepatic cholangiocarcinoma (ICC) and to analyze the sensitivity and specificity in the diagnosis of large and small bile duct cholangiocarcinoma.Methods:Clinical data of 47 patients (22 patients small bile duct and 25 patients large bile duct ICC) diagnosed with ICC at Ningbo Clinical Pathology Diagnosis Center from January 2018 to September 2019 were retrospectively analyzed, including 29 males and 18 females, aged (64.0±11.1) years. Cancer tissue specimens were collected. The expressions of S100P, mucin 5A, mucin 6, estrogen-induced protein pS2, CRP, N-cadherin and CD56 in cancer tissues were detected by immunohistochemical method, and the sensitivity and specificity of these proteins in the diagnosis of small bile duct and large bile duct ICC were analyzed.Results:In 22 patients with small bile duct type ICC, CD56 expression was positive in 12 (54.5%), CRP expression in 22 (100.0%) and N-cadherin expression in 21 (95.5%), large bile duct type ICC were 8.0%(2/25), 28.0%(7/25), 40.0%(10/25). In 25 cases of large bile duct type ICC, S100 calcium-binding protein P expression was positive in 23 cases (92.0%), estrogen-induced protein pS2 expression in 21 (84.0%) and mucin 5A expression in 23 (92.0%), small bile duct type ICC were 9.1%(2/22), 36.4%(8/22), 0. The positive expression rates of CD56, CRP and N-cadherin in small bile duct type ICC were significantly higher than those in large bile duct type ICC, while S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A were lower than those in large bile duct type ICC (all P<0.05). The sensitivity of CD56, CRP and N-cadherin in the diagnosis of small bile duct type ICC were 54.5%, 100.0% and 95.5%, and the specificity were 92.0%, 72.0% and 60.0%, respectively. The sensitivity of S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A in the diagnosis of large bile duct type ICC were 92.0%, 84.0% and 92.0%, and the specificity were 90.9%, 63.6% and 100.0%, respectively. Conclusion:The positive expressions of CD56, CRP, N-cadherin, S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A are of great value in the differential diagnosis of large bile duct type and small bile duct type ICC, and the diagnostic accuracy is reasonable, which could facilitate the accurate histological classification of ICC.

Regional party building has been an important exploration in innovating grassroots party building in recent years.Under the comprehensive implementation of the requirements for party building in the new era,public hospitals have a-chieved the sharing and extension of medical resources through system and mechanism reforms and innovations.Based on the re-gional party building,it has become an inevitable requirement to explore the new era of party building in public hospitals.This study analyzes the current challenges faced by hospitals participating in regional party building work and combines the practical experience of regional party building work in Shuguang Hospital,affiliated to Shanghai University of Traditional Chinese Medi-cine.It promotes paths such as party building leading joint construction,expanding the scope of medical volunteer services,and promoting the deep integration of party building and business work.This will further improve the quality of people's lives,ulti-mately achieving"mutual benefit"through"resource sharing."

Objective To explore the application value of the Plan-Do-Study-Act(PDSA)cycle in reducing the occur-rence of decomposed hospitalization for stroke disease under the Diagnosis Related Group(DRG)payment model and validate the effectiveness of strategies to reduce decomposed hospitalization.Methods Taking stroke cases participating in DRG payment from January 2022 to December 2022 in a tertiary hospital in Tianjin as the baseline,the criteria for decomposed hospitalization were determined based on the"Implementation Rules for DRG/DIP Network Audit(Trial)"issued by the Tianjin Medical Insur-ance Fund Settlement Center.A PDSA cycle plan was developed according to the document content,and the PDSA cycle was im-plemented from January to December 2023.The relationship between the number of decomposed hospitalizations before and after the PDSA cycle was analyzed using SPSS 20.0 to determine the actual application effect.Results After the PDSA cycle,the number of decomposed hospitalizations decreased from1268 cases to26 cases,a total decrease of 97.95%.The number of cases in each target subgroup and the frequency of factors leading to decomposed hospitalization all showed a significant decrease.Con-clusion The PDSA cycle plays a significant role in addressing the problem of decomposed hospitalization for stroke disease under the DRG payment model.It can effectively reduce the occurrence of decomposed hospitalization,improve the quality of medical insurance settlement lists and medical records,and standardize clinical diagnosis and treatment behavior.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

Objective This study aims to investigate the application of the Plan-Do-Check-Act(PDCA)cycle in the Di-agnosis Related Group(DRG)payment system for oncological diseases.Methods We analyzed the factors influencing DRG pay-ment and incorporated the PDCA Cycle in the oncological diseases at a tertiary hospital in Tianjin.The baseline data of cases partic-ipating in DRG payment from April 2022 to September 2022 were compared with the settlement data of cases participating in DRG payment from October 2022 to March 2023.SPSS 20.0 was used to evaluate the impact of data quality in medical record documenta-tion on DRG admission rate,average hospitalization costs,average length of stay,Case Mix Index(CMI)value,and DRG settle-ment rate,so as to assess the effectiveness of the PDCA cycle in DRG payment within the oncological diseases at the hospital.Re-sults Following the PDCA cycle,the DRG admission rate increased from 84.03%to 89.98%,and the cases ineligible for inclu-sion decreased by 22.78%due to mismatched main diagnosis and procedures."Violations of the reporting and coding principles that do not require reporting"and"omission of primary surgical procedure codes"were no longer observed as reasons for failed DRG inclusion.Ambiguous cases with both average hospitalization costs and average length of stay higher than those of normal inclu-sion cases,leading to an increase in the average hospitalization cost from 22 496.56 yuan to 24714.92 yuan,and the average length of stay increased from 7.50 days to 8.13 days.The CMI value increased from 0.96 to 1.08,and the DRG settlement rate increased from 107.93%to 130.67%.Conclusion The PDCA cycle can effectively enhance the quality of medical record documentation,leading to improved quality in medical insurance settlement lists and DRG admission rates.It can help identify operational issues within the de-partment and promote the smooth implementation of DRG payment reform in the oncological department.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.