Prognostic factors of surgical management for heart failure patients with reduced left ventricular ejection fraction.

Objectives: There are many available pharmaceutical and surgical management for Coronary artery disease (CAD) patients. However, coronary artery bypass grafting (CABG) is the preferred treatment modality for CAD patients with low ejection fraction (EF) in view of the more favorable outcomes. This study aimed to determine the associated factors of poor outcomes post-CABG for heart failure patients with reduced left ventricular ejection fraction who underwent on-pump and off-pump CABG. Methods: A retrospective review of CAD patients who underwent isolated on-pump CABG (ONCAB) or off-pump CABG (OPCAB) in Beijing Anzhen Hospital Affiliated with Capital Medical University from January 2013 to March 2021. Only those with confirmed reduced left ventricular ejection fraction (LVEF) ≤40% on preoperative echocardiography were included. By analyzing the clinical and surgical data, postoperative mortality and morbidity, as well as major cardiovascular and cerebrovascular adverse events (MACCE) as endpoints, certain risk factors of the postoperative complications were identified. Results: Out of the 500 patients, 64 developed MACCE, of which 14 (13.6%) occurred in the ONCAB group and 50 (14.0%) in the OPCAB group. Univariate COX regression analysis showed that age ≥65 years, history of diabetes, and preoperative renal insufficiency were independent risk factors for postoperative primary endpoint events in CAD patients with heart failure with reduced ejection fraction (HFrEF). Following the multivariate COX regression analysis, in addition to the above three risk factors, a history of previous percutaneous coronary angiography (PCI) intervention was also a risk factor for the occurrence of the primary endpoints post-CABG. Conclusion: Based on the analysis, significant predictors of post-CABG MACCE in patients with HFrEF included being older than 65 years old, having diabetes, preoperative renal insufficiency, and having previous PCI.

Comparison of Direct and Extraction Immunoassay Methods With Liquid Chromatography-Tandem Mass Spectrometry Measurement of Urinary Free Cortisol for the Diagnosis of Cushing’s Syndrome

Background@#Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. @*Methods@#Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. @*Results@#Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. @*Conclusions@#Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

No-touch technique for harvesting saphenous vein in coronary artery bypass grafting and research progress / 中华胸心血管外科杂志

The saphenous vein has been one of the most commonly used vascular materials for coronary artery bypass grafting(CABG), but the low long-term patency of the vein grafts limits the surgical benefits of CABG. The traditional method of saphenous vein harvesting is more damaging to the venous structures, which has led to the development of no-touch saphenous vein harvesting techniques. In this paper, we review the clinical progress of no-touch saphenous vein in CABG and the potential mechanisms of this technique, to improve the patency of vein grafts by analyzing the latest literature and research progress at the domestic and international level.

Advancement in the relationship between gut microbiota and coronary artery disease / 中国胸心血管外科临床杂志

@#Including gut microbiota and oral microbiota, various microorganisms in different human ecosystem constitute the human microbiota, which play an important role in human metabolism, immunity and maintaining microecological homeostasis. Abnormal changes in gut microbiota known as dysbiosis may lead to metabolic abnormalities and inflammatory changes, which are closely related to disease states including hypertension, diabetes, inflammatory bowel disease, and autoimmune diseases. The main cause of coronary artery disease is coronary atherosclerosis, a chronic and progressive inflammatory disease. Many evidences have shown that there is a correlation between gut microbiota and coronary artery disease. Therefore, we aim to review the relationship between gut microbiota and coronary artery disease, and discuss the possible research directions and application prospects.

Mid- and long-term efficacy of off-pump coronary artery bypass grafting in elderly patients with coronary artery disease complicated with moderate ischemic mitral regurgitation / 中国胸心血管外科临床杂志

@# Objective     To analyze the efficacy of off-pump coronary artery bypass grafting (OPCABG) in elderly patients with coronary artery disease complicated with moderate ischemic mitral regurgitation. Methods     The clinical data of patients aged≥70 years with coronary artery disease complicated with moderate mitral regurgitation, and undergoing OPCABG from January 2009 to January 2020 in Beijing Anzhen Hospital were retrospectively analyzed. The echocardiographic indicators of the patients were compared preoperatively, postoperatively before discharge and during the follow-up. Results     Finally 239 patients were enrolled. There were 136 males and 103 females, aged 74.1±3.2 years. Before postoperative discharge, 49 (20.5%) patients had no mitral regurgitation, 144 (60.3%) mild regurgitation, 46 (19.2%) moderate regurgitation, and 0 severe regurgitation. The area of mitral regurgitation was significantly improved (2.5±1.8 cm2 vs. 5.6±1.0 cm2, P<0.001). There were 10 (4.2%) patients of hospital death, 23 (9.6%) of low cardiac output, 3 (1.3%) of myocardial infarction, and 8 (3.3%) of nervous system injury after operation. As a result, 208 (90.8%) patients were followed up and the mean follow-up time was 3.4 years (range 1-9 years). The cumulative survival rates at postoperative 2, 4, 6, and 8 years were 95.8%, 88.0%, 78.4%, and 73.1%, respectively. Postoperative follow-up showed significant improvements compared with those before surgery in the area of mitral regurgitation, left ventricular ejection fraction, left ventricular end-diastolic and left ventricular end-systolic diameters (all P<0.05). Duirng the follow-up, the major adverse cardiac and cerebrovascular events were all cause death in 22 (10.6%) patients, including cardiac death in 17 (8.2%) patients, myocardial infarction in 7 (3.4%) patients, heart failure in 24 (11.5%) patients, cerebrovascular events in 11 (5.3%) patients, re-hospitalization due to heart disease in 23 (11.1%) patients, and none of the patients with myocardial infarction were revascularized. Conclusion     The mid- and long-term outcomes of OPCABG in the treatment for elderly patients with coronary artery disease complicated with moderate ischemic mitral regurgitation is good.

Morin ameliorates chronic obstructive pulmonary disease by inhibiting the expression of MMP9 / 安徽医科大学学报

Objective To investigate the effects of morin on chronic obstructive pulmonary disease(COPD)animal and cell model through the regulation of matrix metalloproteinase-9(MMP9).Methods SwissTargetPrediction da-tabase was used to predict the genetargets of morin,GeneCards,OMIMand DisGenet databases were used to predict the risk genes of COPD,the intersection of COPD-related gene targets and morin gene targets was obtained by using Venny online website;Protein-protein interaction(PPI)analysis was performed using the String database,and to-pological analysis was performed by Cytoscape 3.8.2 software.Molecular docking was used to validate the interac-tion between the drug components and gene targets;COPD rat models were constructed to verify the therapeutic effects of morin om COPD rat models.The COPD cell model was established to interfere with the expression of MMP9 in the cells.COPD cell models were established and the expression of MMP9 in cells was intervened;flow cytometry was used to detect cell apoptosis rate;ELISA was used to measure the concentration of inflammatory fac-tors.Results The Swiss Target Prediction database predicted 96 gene targets of morin.GeneCards,OMIM,and DisGenet databases predicted 7 122 gene targets of COPD,intersection analysis identified 67 common gene targets between morin and COPD.Topological analysis revealed that the top 5 gene targets with strongest interactions a-mong the intersected targets were SRC,MMP9,MMP2,PTGS2,and FURIN;Molecular docking results showed the best binding activity between MMP9 and morin;animal experiments showed that morin improved respiratory function parameters and lung tissue pathological damage,and inhibited MMP9 expression in COPD rats(P＜0.05);Cell experiments showed that morin increased cell viability in COPD cell models and inhibited MMP9 ex-pression(P＜0.05).In addition,morin inhibited cell apoptosis and expression of inflammatory factors in the COPD cell model,but this effect was reversed by overexpression of MMP9(P＜0.05).Conclusion Morin can improve apoptosis and and expression of inflammatory cytokines in COPD cell model,reduce lung tissue pathologi-cal changes by inhibiting MMP9 expression.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Discussion on internal fixation of Hoffa fractures / 中国骨伤

Hoffa fracture is an unstable intra-articular fracture with significant redisplacement tendency. It is easy to be missed diagnosis when accompanied by distal intercondylar or supracondylar fracture of femur. CT scan is the gold standard for the diagnosis of Hoffa fracture. The treatment principles are anatomic reduction of the articular surface, reliable internal fixation, and early functional activity. At present, the main treatment is arthroscopic screw fixation. During screw fixation, the tail cap of screw should be buried, resulting in non-healing iatrogenic injury of articular cartilage. In the early postoperative functional activity of knee joint, fracture block was repeatedly subjected to backward and upward shear force under the action of the tibial plateau, which is the main reason for the failure of internal fixation. Plate assisted screw fixation could increase local mechanical stability, but it still cannot avoid the defects of iatrogenic cartilage injury. At the same time, plate molding is required during the operation due to the absence of special anatomical plates, resulting in increased surgical trauma and time-consuming surgery. The ideal fixation method for Hoffa fracture should include:(1) Avoid iatrogenic injury of articular surface cartilage. (2) With the rear anti-shear barrier plate function.(3) The internal fixator is closer to the load interface, so as to obtain greater load and better fixed strength.

Cangxi Tongbi Capsules promote chondrocyte autophagy by regulating circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit development of knee osteoarthritis / 中国中药杂志

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1β(IL-1β) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1β showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.

Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Research progress on"one-two punch"strategy in the therapy of glioma / 中国肿瘤临床

Glioblastoma(GBM)originates from glial cells,and complete surgical resection followed by radiotherapy and chemotherapy is the current standard treatment.However,gliomas are subjected to not only accelerated cell death after radiotherapy and chemotherapy but also cellular senescence.Senescent cells produce a senescence-associated secretory phenotype(SASP),which has a dual effect on the tumor microenvironment.The"one-two punch"strategy of specifically eliminating senescent cells and inhibiting SASP-derived secretions provides a new direction for tumor therapy.In this article,we review the mechanisms that mediate tumor cellular senescence and SASP,the elimina-tion of senescent cells by senolytics for SASP inhibition,and the current situation of the"one-two punch"strategy for the treatment of glioma.

Characteristics of bone marrow compensatory erythropoiesis in hereditary spherocytosis / 中华血液学杂志

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Serum brain-derived neurotrophic factor predicts post-stroke cognitive impairment in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between serum brain-derived neurotrophic factor (BDNF) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke, and to evaluate its predictive value for PSCI.Methods:Patients with acute ischemic stroke admitted to the Affiliated Hospital of Jining Medical University from April 2018 to September 2020 were prospectively enrolled. Cognitive impairment was assessed by Montreal Cognitive Assessment (MoCA) at 3 months after onset. Multivariate logistic analysis was used to determine the independent correlation between serum BDNF and PSCI, and receiver operating characteristics (ROC) curve was used to evaluate its predictive value for PSCI. Results:A total of 511 patients with acute ischemic stroke were enrolled, including 332 males (65.0%), aged 60.67±10.18 (range 49-80) years. The median score of the National Institutes of Health Stroke Scale (NIHSS) at the baseline was 5.0 (interquartile range 2.7-6.7), and 413 patients (80.8%) had anterior circulation stroke. The median of serum BDNF was 11.54 μg/L (interquartile range 6.13-16.25 μg/L). PSCI occurred in 310 patients (60.7%). Univariate analysis showed that there were significant differences in age, history of previous transient ischemic attack, baseline NIHSS score and serum BDNF between the PSCI group and the non-PSCI group (all P<0.05). Multivariate logistic analysis showed that there was a significant independent correlation between serum BDNF and PSCI (odds ratio 0.514, 95% confidence interval 0.356-0.807; P=0.005). ROC curve analysis showed that the area under the curve of serum BDNF predicting PSCI was 0.863 (95% confidence interval 0.830-0.896; P<0.001). The best cut-off value was 10.78 μg/L, and the sensitivity and specificity were 74.9% and 86.8% respectively. Conclusion:Higher baseline serum BDNF was a protective factor for PSCI and had good predictive value for PSCI.

Study of quantitative flow ratio-guided surgical coronary artery revascularization strategy / 中华胸心血管外科杂志

Objective:To explore the feasibility of applying quantitative flow ratio(QFR) to assess the degree of coronary artery functional stenosis before surgery, and to guide coronary artery bypass grafting(CABG) revascularization strategy.Methods:The study prospectively included a total of 154 patients who were electively treated with CABG in the 11th ward of the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 2019 to September 2020, and their coronary angiography visually showed stenosis of the coronary artery to perform QFR analysis to know the diseased blood vessels. For functional stenosis, the surgeon was blinded to the results of QFR analysis before surgery. Collect its baseline data, perioperative data and recent clinical outcomes for summary analysis.Results:One year later, the coronary artery CTA showed that the occlusion rate of functionally significant disease(QFR<0.8) was 5.5%, and that of non-functionally significant disease(QFR≥0.8) was 15.6%. There was no difference in angina class or repeat interventions between patients with or without occluded bypass grafts.Conclusion:According to QFR analysis, coronary arteries with functional non-significant disease have a higher risk of grafts failure than those with functionally significant disease. For coronary arteries with negative QFR lesions, the risk of occlusion of arterial grafts is higher than that of venous. However, this finding is not significantly related to clinical prognosis, because patients with patency or occlusion of the grafts in non-significant lesions have not found excessive angina pectoris or repeated coronary interventions. QFR-guided selection of coronary surgery strategies is safe and feasible.

Risk factors of early death and long-term outcomes in myocardial infarction complicated with ventricular septal rupture / 中华老年医学杂志

Objective:To analysis the risk factors of early death and long-term outcomes of myocardial infarction complicated with ventricular septal rupture.Methods:A total of 135 patients with myocardial infarction complicated with ventricular septal rupture in Beijing Anzhen Hospital from January 2008 to December 2020 were retrospectively analyzed.According to the survival or death within 30 days after ventricular septal rupture, the patients were divided into the early survival group(n=71)and the early death group(n=64). The clinical characteristics of the two groups were observed, and the risk factors for early death group were analyzed.The long-term outcomes of the surgery group(n=69)and the non-surgery group(n=66)was analyzed.Results:The early mortality rate of patients with myocardial infarction complicated with ventricular septal rupture was 47.4%(64/135). Univariate analysis showed that age, sex, white blood cell count, platelet count, C-reactive protein level, left ventricular end-diastolic diameter, abnormal liver function, pulmonary infection, no surgery repair and Killip grade ≥3 were associated with early death as compared with the early survival group(all P<0.05). Multivariate regression analysis showed that no surgery repair( OR=16.103, 95% CI: 4.400-58.930, P<0.001)and Killip≥3 grade( OR=9.014, 95% CI: 2.506-32.428, P=0.001)and abnormal liver function( OR=5.171, 95% CI: 1.388-19.264, P=0.014)were independent risk factors for early death in patients with myocardial infarction complicated with ventricular septal rupture.During follow-up of 1.0 to 11.8(median 3.2)years, the 2-year and 10-year cumulative survival rates were significantly higher in the surgery group than in the non-surgery group(76.7% vs.16.7%, P<0.001; 73.1% vs.16.7%, P<0.001). Conclusions:No surgical repair, Killip grade ≥3 and abnormal liver function are independent risk factors for early death in patients with myocardial infarction complicated with ventricular septal rupture.The long-term outcomes of surgical treatment for myocardial infarction complicated with ventricular septal rupture is good.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 variants

SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.

Adult Age Estimation of CT Image Reconstruction of the Laryngeal Cartilages and Hyoid Bone Based on Data Mining / 法医学杂志

Objective To explore the feasibility of the CT image reconstruction of laryngeal cartilage and hyoid bone in adult age estimation using data mining methods. Methods The neck thin slice CT scans of 413 individuals aged 18 to <80 years were collected and divided into test set and train set, randomly. According to grading methods such as TURK et al., all samples were graded comprehensively. The process of thyroid cartilage ossification was divided into 6 stages, the process of cricoid cartilage ossification was divided into 5 stages, and the synosteosis between the greater horn of hyoid and hyoid body was divided into 3 stages. Multiple linear regression model, support vector regression model, and Bayesian ridge regression model were developed for adult age estimation by scikit-learn 0.17 machine learning kit （Python language）. Leave-one-out cross-validation and the test set were used to further evaluate performance of the models. Results All indicators were moderately or poorly associated with age. The model with the highest accuracy in male age estimation was the support vector regression model, with a mean absolute error of 8.67 years, much higher than the other two models. The model with the highest accuracy in female adult age estimation was the support vector regression model, with a mean absolute error of 12.69 years, but its accuracy differences with the other two models had no statistical significance. Conclusion Data mining technology can improve the accuracy of adult age estimation, but the accuracy of adult age estimation based on laryngeal cartilage and hyoid bone is still not satisfactory, so it should be combined with other indicators in practice.