ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure （CHF） and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction （TAC）. Eight of the 50 SD rats were randomly selected as the sham group， and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model， trimetazidine （6.3 mg·kg^-1）， and Yiqi Wenyang Huoxue Lishui components （60 mg·kg^-1 total saponins of Astragali Radix， 10 mg·kg^-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma， 190 mg·kg^-1 aqueous extract of Lepidii Semen， and 100 mg·kg^-1 cinnamaldehyde） groups. The rats were administrated with corresponding agents by gavage， and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg^-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， hypersensitive troponin（cTnI）， creatine kinase （CK）， lactate dehydrogenase （LD）， free fatty acids （FFA）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The colorimetric assay was employed to measure the levels of adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta （ATP5D）， glucose transporter 4 （GLUT4）， and carnitine palmitoyltransferase-1 （CPT-1）. The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ. ResultsCompared with the sham group， the model group showed a loosening arrangement of cardiac fibers， fracture and necrosis of partial cardiac fibers， inflammatory cells in necrotic areas， massive blue fibrotic tissue in the myocardial interstitium， increased collagen fiber area and myocardial fibrosis， destroyed mitochondria， myofibril disarrangement， sparse myofilaments， and fractured and reduced cristae. In addition， the rats in the model group showed declined ejection fraction （EF） and fractional shortening （FS）， risen left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs）， elevated levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， lowered level of SOD， down-regulated protein levels of GLUT4 and CPT-1， decreased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and declined levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. Compared with the model group， the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue， risen EF and FS， declined LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs， lowered levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， elevated level of SOD， up-regulated protein levels of GLUT4 and CPT-1， increased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and elevated levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function， reduce myocardial injury， regulate glucose and lipid metabolism， optimize the utilization of substrates， and alleviate the damage of mitochondrial structure and function， thus improving the energy metabolism of the myocardium in the rat model of CHF.

Objective:To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns.Methods:Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development.Results:Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95% CI: 1.03-1.71; high LDL-C: OR=1.35, 95% CI: 1.05-1.75; low HDL-C: OR=1.45, 95% CI: 1.19-1.77; high TG: OR=1.50, 95% CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed ( P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias ( OR=2.02, 95% CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C ( OR=3.54, 95% CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions:A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Objective To explore the effect of deep learning image reconstruction(DLIR)algorithm combined with"double low"[low voltage(kV)and low contrast agent dosage]technique on the image quality of coronary computed tomography angiography(CCTA)in overweight patients compared with adaptive statistical iterative reconstruction(ASIR-V)and filtered back projection(FBP).Methods Fifty-two patients with body mass index(BMI)between 25.1 kg/m2and 28 kg/m2 who underwent CCTA scanning were prospectively selected,all of whom scanned on a GE Revolution APEX-CT with a tube voltage of 80 kV,a smart mA(500-1 300 mA),a noise index of 30,and a contrast dosage of 0.5 mL/kg;four groups of images were reconstructed for each patient,FBP,50％ASIR-V,DLIR-M,and DLIR-H.The CT and SD values of the aorta(AO)root,the proximal segment of the right coronary artery(RCA),the left circumflex(LCX),the left anterior descending branch(LAD)and the pericardial fat were measured,and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two doctors experienced in the diagnosis of cardiovascular disease were selected to subjectively score the reconstructed images using a double-blind method.The SD value,SNR value,CNR value and subjective scores of images in the four groups were compared.Results In the objective image quality evaluation,there were statistically significant differences in SD value,SNR value and CNR value of reconstructed images in the four groups(P＜0.05).As the four groups of reconstruction algorithms FBP,50％ASIR-V,DLIR-M,and DLIR-H were changed sequentially,the image SD value gradually decreased,the SNR value and CNR value gradually increased,and the DLIR-H group had the lowest SD value and the highest SNR and CNR values.In the subjective image quality evaluation,the subjective scores of the two doctors had good consistency(Kappa value=0.900),and the difference between them was statistically significant(P＜0.001).The subjective scores of DLIR-M and DLIR-H groups were higher.Conclusion DLIR algorithm combined with"double-low"technique can significantly improve the CCTA image quality of overweight patients,which is better than 50％ASIR-V and FBP.

Objective To study the clinical characteristics and related factors affecting the severity of acute tinnitus in patients.Methods A retrospective analysis was conducted on the data of 319 patients with acute tinni-tus.All patients had detailed case history,including basic patient information,tinnitus location,course of disease,acoustic characteristics of tinnitus,hearing loss,combined headache,dizziness,aural fallness,earache and other symptoms,as well as accompanying clinical diseases.All patients completed the tinnitus handicap inventory(THI),generalized anxiety disorder(GAD-7),patient health questionnaire(PHQ-9),pittsburgh sleep quality index(PSQI),hyperacusis questionnaire(HQ),type D personality scale-14(DS-14),etc.The mild tinnitus group was determined based on a THI score of ≤36.The moderate tinnitus group was determined based on a THI score of 38～56.The severe to extremely severe tinnitus group was determinded based on THI 56～100.THI grouping was used as the dependent variable and the above factors as independent variables.The correlation between each factor and the severity of acute tinnitus was analyzed using ordered multinomial logistic regression.Results Among 319 patients with acute tinnitus,158(49.5％)were in the mild tinnitus group,and 72(22.6％)were in the moderate tinnitus group,and 89(27.9％)were in severe to extremely severe tinnitus group.Ordered multinomial logistic re-gression analysis found that hyperacusis(OR=3.921),anxiety(OR=2.495),depression(OR=2.921),and D-type personality(OR=0.349)were associated with the severity of acute tinnitus(P＜0.05),with more serere tin-nitus in these patients.Conclusion Hyperacusis,anxiety,depression,and D-type personality may be factors that affect the severity of acute tinnitus,so high attention should be paid when treating patients with acute tinnitus.

Objective To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.Methods KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues,4 gastric adenocarcinoma cell lines(MKN-28,HGC-27,CRL-5822,and SNU-1)and normal human gastric mucosal GES-1 cells.In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression,cell proliferation,migration,invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay,Transwell migration and invasion assays,and Western blotting.In BALB/c-nude mice,HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.Results Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells.In HGC-27 cells,KHSRP knockdown significantly inhibited cell proliferation,migration and invasion,while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells.In nude mice,inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight,slower cell proliferation rate and fewer lung metastatic foci,and KHSRP-overexpressing SNU-1 cells produced the opposite results.KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3,which were obviously increased in KHSRP-overexpressing SNU-1 cells.Conclusion High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

Objective To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.Methods KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues,4 gastric adenocarcinoma cell lines(MKN-28,HGC-27,CRL-5822,and SNU-1)and normal human gastric mucosal GES-1 cells.In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression,cell proliferation,migration,invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay,Transwell migration and invasion assays,and Western blotting.In BALB/c-nude mice,HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.Results Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells.In HGC-27 cells,KHSRP knockdown significantly inhibited cell proliferation,migration and invasion,while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells.In nude mice,inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight,slower cell proliferation rate and fewer lung metastatic foci,and KHSRP-overexpressing SNU-1 cells produced the opposite results.KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3,which were obviously increased in KHSRP-overexpressing SNU-1 cells.Conclusion High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.

Objective To explore the clinical efficacy of recombinant human prourokinase during emergency coronary intervention (PCI) in patients with acute inferior wall ST segment elevation myocardial infarction (STEMI) without reflow or slow blood flow.Methods Eighty patients with acute inferior wall STEMI admitted to Xinyi People's Hospital from January 2022 to December 2023 were selected.The patients were divided into two groups,40 cases in each group.The control group patients accepted PCI after receiving 100μg nitroglycerin or nitroprusside via catheter;On the basis of control group,the observation group patients received 20mg recombinant human prourokinase via catheter until infarct related artery,and PCI was performed.Using thrombolysis in myocardial infarction (TIMI) blood flow grading method,compared the immediate myocardial perfusion after surgery.Results Comparison of immediate TIMI blood flow grading between two groups of patients during surgery,with grades ranging from level 0 to 1:1 case (2.5％) in observation group and 7 cases (17.5％) in control group.The difference between two groups was statistically significant (P<0.05);Level 2:3 cases (7.5％) in observation group and 8 cases (20.0％) in control group.There was no statistically significant difference between two groups (P>0.05);Level 3:36 cases (90.0％) in observation group and 25 cases (62.5％) in control group.The difference between two groups was statistically significant (P<0.05).Conclusion Recombinant human prourokinase can effectively improve the coronary blood flow of infarct related artery during emergency PCI in patients with acute inferior wall STEMI,improve myocardial ischemia,and do not increase adverse reactions such as bleeding,which is of great significance for improving patient's prognosis.

Objective:To compare the efficacy of single-agent versus multi-agent adjuvant chemotherapy after radical gastrectomy for elderly patients with stage Ⅲ gastric cancer.Methods:The propensity score matching and retrospective cohort study were conducted. The clinicopatholo-gical data of 456 elderly patients with stage Ⅲ gastric cancer who underwent D 2 radical resection in the Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine from January 2016 to December 2020 were collected. There were 343 males and 113 females, aged 71(range, 65?89)years. Of the 456 patients, 274 cases undergoing single-agent adjuvant chemotherapy after surgery were divided into single-agent chemotherapy group, 182 cases undergoing double-agent or triple-agent adjuvant chemotherapy after surgery were divided into multi-agent chemotherapy group. Observa-tion indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) adverse events during chemotherapy; (3) follow-up. Propensity score matching was done by the 1∶1 ratio, with the caliper value of 0.05. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parameter rank sum test. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 456 patients, 306 cases were successfully matched, including 153 cases in the single-agent chemotherapy group and 153 cases in the multi-agent chemotherapy group. The elimination of age, age-adjusted Charlson comorbidity index, pathological TNM staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Adverse events during chemotherapy. In terms of hematological adverse events, 6 cases in the single-agent chemotherapy group and 16 cases in the multi-agent chemotherapy group had neutropenia, showing a significant difference in the neutropenia ( χ2=4.90, P<0.05). In terms of non-hematological adverse events, cases with anorexia and nausea were 77 and 50 for the single-agent chemotherapy group, versus 96 and 69 for the multi-agent chemotherapy group, showing significant differences between the two groups ( χ2=4.80, 4.96, P<0.05). (3)Follow-up. All the 306 patients were followed up for 48(range, 8?61)months. The 5-year overall survival rates of the single-agent chemotherapy group and the multi-agent chemotherapy group were 36.08% and 38.31%, respectively, showing no significant difference between the two groups ( hazard ratio=0.93, 95% confidence interval as 0.70?1.20, P>0.05). Results of further analysis showed that the 5-year overall survival rates were 32.41% and 39.40% for 97 patients of the single-agent chemotherapy group and 97 patients with double-agent regimen of the multi-agent chemotherapy group, respectively, showing no significant difference between them ( hazard ratio=1.20, 95% confidence interval as 0.82?1.70, P>0.05). The 5-year overall survival rates were 43.15% and 37.11% for 56 patients of the single-agent chemotherapy group and 56 patients with triple-agent regimen of the multi-agent chemotherapy group, respectively, showing no significant difference between them ( hazard ratio=0.81, 95% confidence interval as 0.65?1.00, P>0.05). Conclusions:For adjuvant chemotherapy in elderly patients with stage Ⅲ gastric cancer, there is no significant survival advantage of double-agent or triple-agent chemotherapy over single-agent oral chemotherapy. However, there is a higher incidence of neutropenia, anorexia, ausea.