Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Objective:To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation.Methods:A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University.Results:① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1β, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [ P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 ( P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions:Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

Objective To explore the postoperative characteristics and management experience of patients with coronavirus disease 2019 (COVID-19) undergoing cardiac and vascular surgery. Methods From December 7, 2022 to January 5, 2023, the patients with COVID-19 who were admitted to Cardiovascular Hospital Affiliated to Kunming Medical University and underwent cardiac and vascular surgery were selected. The clinical history, surgical information, postoperative recovery process and treatment plan were analyzed retrospectively. Results There were 18 patients in this group, including 11 (61.1%) males and 7 (38.9%) females, with an average age of 58.1±10.9 years. There were 7 patients of hypertension, 5 patients of diabetes, 3 patients of respiratory diseases, and 2 patient of chronic renal insufficiency. There were 5 (27.8%) patients receiving emergency operations and 13 (72.2%) elective operations. All the 18 patients underwent cardiac and vascular surgery in the period of COVID-19, and the time between the last positive nucleic acid test and the surgery was 1.50 (1.00, 6.25) days. There were 8 patients of pulmonary imaging changes, including 3 patients with chest patch shadow, 3 patients with thickened and disordered lung markings, and 2 patients with exudative changes before operation. Antiviral therapy was not adopted in all patients before operation. Three patients were complicated with viral pneumonia after operation, including 2 patients with high risk factors before operation, who developed into severe pneumonia after operation, and underwent tracheotomy. One patient with thrombus recovered after anticoagulation treatment. Another patient of mild pneumonia recovered after antiviral treatment. The other 15 patients recovered well without major complications. There was no operation-related death in the whole group. One patient died after surgery, with a mortality rate of 5.6%. Conclusion Patients with COVID-19 are at high risk of cardiac and vascular surgery, and patients with high-risk factors may rapidly progress to severe pneumonia. Patients with preoperative lung imaging changes or other basic visceral diseases should consider delaying the operation. Early antiviral combined with immunomodulation treatment for emergency surgery patients may help improve the prognosis.

Objective To explore the postoperative characteristics and management experience of patients with coronavirus disease 2019 (COVID-19) undergoing cardiac and vascular surgery. Methods From December 7, 2022 to January 5, 2023, the patients with COVID-19 who were admitted to Cardiovascular Hospital Affiliated to Kunming Medical University and underwent cardiac and vascular surgery were selected. The clinical history, surgical information, postoperative recovery process and treatment plan were analyzed retrospectively. Results There were 18 patients in this group, including 11 (61.1%) males and 7 (38.9%) females, with an average age of 58.1±10.9 years. There were 7 patients of hypertension, 5 patients of diabetes, 3 patients of respiratory diseases, and 2 patient of chronic renal insufficiency. There were 5 (27.8%) patients receiving emergency operations and 13 (72.2%) elective operations. All the 18 patients underwent cardiac and vascular surgery in the period of COVID-19, and the time between the last positive nucleic acid test and the surgery was 1.50 (1.00, 6.25) days. There were 8 patients of pulmonary imaging changes, including 3 patients with chest patch shadow, 3 patients with thickened and disordered lung markings, and 2 patients with exudative changes before operation. Antiviral therapy was not adopted in all patients before operation. Three patients were complicated with viral pneumonia after operation, including 2 patients with high risk factors before operation, who developed into severe pneumonia after operation, and underwent tracheotomy. One patient with thrombus recovered after anticoagulation treatment. Another patient of mild pneumonia recovered after antiviral treatment. The other 15 patients recovered well without major complications. There was no operation-related death in the whole group. One patient died after surgery, with a mortality rate of 5.6%. Conclusion Patients with COVID-19 are at high risk of cardiac and vascular surgery, and patients with high-risk factors may rapidly progress to severe pneumonia. Patients with preoperative lung imaging changes or other basic visceral diseases should consider delaying the operation. Early antiviral combined with immunomodulation treatment for emergency surgery patients may help improve the prognosis.

Objective:To analyze the status quo, hotspots and fronts of emergency nursing training research at home and abroad in the past ten years, and to provide reference and ideas for the efficient development of emergency nursing training in China.Methods:CiteSpace 6.2.R2 software was used to visually analyze the Chinese and English literatures on emergency nursing training included in CNKI and Web of Science core databases from January 1, 2013 to June 1, 2023.Results:A total of 1 177 Chinese literatures and 1 163 English literatures were included. The number of foreign articles in this field increased year by year, while the number of domestic articles showed a downward trend since 2018. There were many stable core author groups and core institution groups in foreign countries, while there was less cooperation among domestic authors and institutions. The common research hotspots and frontiers at home and abroad focused on broadening the training audience of emergency nursing, innovating the training methods of emergency nursing, strengthening the evaluation of the effect of emergency nursing training, and paying attention to the training experience and needs of nurses. Foreign researches also focused on specialized nurses, interprofessional education and nurses′mental health, etc, and the research direction was diversified.Conclusions:The development stages of emergency nursing training researches at home and abroad are different, and the research hotspots are different. In the future, we should learn from foreign research, strengthen interdisciplinary cooperation, improve the depth and breadth of research, and strengthen the cooperation between authors, institutions and countries to promote the high-quality development of emergency nursing training research in China.

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 analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Objective:This work aims to analyze the relationship between the 14 weeks′ Infliximab (IFX) treatment trough blood-concentration of IFK and antibodies to infliximab (ATI) concentration and mucosal healing and infusion reactions in the treatment of Crohn disease (CD).Methods:A total number of 119 CD patients who started IFX treatment in DrumTower Hospital affiliated to Nanjing University Medical School from June 2018 to August 2022 were retrospectively included. General data, endoscopic scores, laboratory tests, 14 weeks′ IFX treatment trough concentration and ATI, as well as endoscopic reexamination and clinical responses during follow-up were collected. According to the endoscopic examination results at (32±4) weeks, the two groups′ patients were divided into the mucosal healing group and non-mucosal healing group. The 14 week IFX trough concentration and ATI situation of the two groups were compared. Multiple logistic regression analysis was applied to analyze the risk factors of (32±4) weeks mucosal healing, using (32±4) weeks mucosal healing as the categorical variable, receiver operating curve (ROC) was obtained, and the optimal critical value of 14 week IFX trough concentration was selected.Result:The results of the 14 weeks′ time point indicated that the end-point IFX concentration and baseline albumin concentration in the mucosal healing group ( n=70 cases) were all significantly higher than those in the non-mucosal healing group ( n=49 cases), with values of 5.0 (2.8, 8.7) μg/ml vs 2.2 (0.3, 4.3) μg/ml, (38.7±3.5) g/L vs (36.6±3.8) g/L, respectively. The 14 week effective trough IFX concentration of (32±4) weeks mucosal healing was 2.90 μg/ml, AUC value is 0.704. Multivariate logistic regression analysis showed that 14 week trough IFX concentration≥2.9 μg/ml ( OR=5.369, 95% CI 2.42-11.92) and baseline Alb≥35 g/L ( OR=7.378, 95% CI 2.18-24.99) were significantly correlated with mucosal healing. The positive rate of ATI at 14 weeks′ time-point was 15.1%, and the trough IFX concentration of all the patients with moderate to high concentrations of ATI ( n=21 cases) was<0.4 μg/ml. Twelve patients (10.1%) experienced infusion reactions, and 53 patients (44.5%) had discontinued IFX. Conclusion:The 14 week trough IFX concentration is closely related to (32±4) week endoscopic mucosal healing.

Objective:To explore the accuracy of mpMRI combined with Partin table, MSKCC nomogram and CAPRA score in predicting extracapsular extension and seminal vesicle invasion of prostate cancer.Methods:From January 2016 to June 2021, a total of 178 patients who underwent laparoscopic radical prostatectomy were selected. The average age of patients was (68.3±3.5) years, the average preoperative PSA level was (24.5±7.1)ng/ml, and the average percentage of positive cores in biopsy was 44.3%. The clinical T 1c stage was determined in 67 cases (37.6%), T 2a in 69 cases (38.8%) and T 2b-2c in 42 cases(23.6%). Biopsy Gleason score of 3+ 3=6 was found in 45 cases(25.3%), 3+ 4=7 in 41 cases(23.0%), 4+ 3=7 in 26 cases(14.6%), 8 with different combinations in 36 cases(20.2%), and 9 or 10 in 30 cases(16.9%). According to preoperative PSA level, biopsy Gleason score, clinical stage, age, total biopsy cores and positive cores, the posibility of extracapsular extension and seminal vesicle invasion were predicted using 2012-version Partin table and MSKCC nomogram. CAPRA score of each patient was calculated. The prediction schemes were built as follows: ①mpMRI alone, ②mpMRI combined with Partin scale, ③mpMRI combined with MSKCC nomogram, ④mpMRI combined with CAPRA score. The results of each prediction scheme were compared with postoperative pathological reports. Logistic regression analysis was used to evaluate the relationship between predictive results and postoperative pathological outcomes. The receiver operating characteristic curve of each prediction scheme was drawn. The area under curve was used to compare the predictive accuracy of each combination scheme for the pathological results of prostate cancer. The decision analysis curve of each prediction scheme was drawn. The clinical benefits of each scheme were analyzed by comparing the net return under different risk thresholds. Results:mpMRI predicted extracapsular extension in 21 cases(11.8%) and seminal vesicle invasion in 16 cases(9.0%). The postoperative pathological results reported extracapsular extension in 27 cases(15.2%) and seminal vesicle invasion in 39 cases(21.9%). Logistic regression analysis showed that mpMRI and clinical scales were predictors related to the pathological results of prostate cancer( P<0.05). The receiver operating characteristic curve of each scheme showed that the area under curve for predicting extracapsular extension by using mpMRI, mpMRI combined with Partin table, mpMRI combined with MSKCC nomogram and mpMRI combined with CAPRA score were 0.599, 0.652, 0.763 and 0.780, respectively, and the area under curve for predicting seminal vesicle invasion were 0.607, 0.817, 0.826 and 0.820, respectively. Compared with simple application of mpMRI, except that the scheme of mpMRI combined with Partin table had no obvious advantage in predicting extracapsular extension( P=0.117), any other combined scheme had higher prediction accuracy( P<0.01). mpMRI combined with MSKCC nomogram or CAPRA score was better than mpMRI combined with Partin table in predicting extracapsular invasion ( P<0.01). There was no significant difference in predicting seminal vesicle invasion among these three combination schemes ( P>0.05). The net income of the combined prediction scheme was higher than that of using mpMRI alone under any risk threshold. The scheme of using mpMRI combined with MSKCC nomogram had the highest net income. Conclusions:mpMRI combined with clinical scales has good accuracy in predicting pathological characteristics of prostate cancer in Chinese population. Compared with other schemes in this study, the combination scheme of mpMRI combined with MSKCC nomogram has the highest prediction accuracy.