Objective:To analysis the risk factors for major adverse cardiovascular event (MACE) in pregnant women with valvular heart disease (VHD) and to construct a risk prediction model.Methods:The clinical data of 245 pregnant women with VHD who were hospitalized in Beijing Anzhen Hospital from January 1, 2012, to June 1, 2023 were retrospectively analyzed, including general information, pre-pregnancy and pregnancy-associated cardiac conditions, and MACE. Univariate analysis and logistic regression models were employed to identify risk factors for MACE during pregnancy among pregnant women with VHD. Furthermore, a predictive model was constructed and internal validation was conducted using bootstrap techniques.Results:(1) Among 245 pregnant women with VHD, the incidence of MACE was 18.0% (44/245), and the most common MACE was heart failure (61.4%, 27/44). The mitral valve was the most frequently affected valve (64.9%, 159/245). Prior to pregnancy, the most common type of valve surgery undertaken was mechanical valve replacement, representing 31.4% (77/245) of surgeries. In contrast, among those pregnant women who did not undergo valve surgery before pregnancy, the most common lesion type was mitral regurgitation (17.6%, 43/245). (2) Comparing the maternal and infant outcomes of warfarin, low molecular weight heparin (LMWH) and LMWH sequential with warfarin, the fetal loss rate (36%, 15/42) and malformation rate (7%, 3/42) were the highest, but the MACE rate (12%, 5/42) was the lowest in warfarin group. The fetal loss rate (1/19), malformation rate (1/19) and artificial valve thrombosis rate (0) of LMWH sequential with warfarin were the lowest, and the fetal loss rate and artificial valve thrombosis rate of the three anticoagulation methods were statistically significant (all P<0.05). (3) There were no significant differences in gestational age, age of diagnosis of heart disease, weight at delivery, pre-pregnancy body mass index, proportion of multiparous women and chronic medical history between women with MACE and those without MACE (all P>0.05). (4) Binary logistic regression analysis identified the following as risk factors for MACE during the second trimester of pregnancy among pregnant women with VHD: pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH during pregnancy, and arrhythmia (all P<0.05). Based on the results of multivariate analysis, a receiver operating characteristic curve was constructed, with an area under the curve of 0.837, indicating good discriminative ability. The calibration plot demonstrated a close alignment between the standard curve and the calibration prediction curve, suggesting excellent calibration of the model. Conclusions:Pregnant women with VHD are at a high risk of experiencing MACE during gestation. Five risk factors, including pre-pregnancy cardiac symptoms, history of corrective surgery for congenital heart disease, pregnancy risk grade Ⅴ, anticoagulation with LMWH, and arrhythmia, could aid in identifying high-risk pregnant women.

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

Objective:To investigate the clinical characteristics and pregnancy outcomes in pregnant women with left ventricular non-compaction (LVNC).Methods:The clinical data of seven pregnant women with LVNC from January 2011 to December 2021 in Beijing Anzhen Hospital,Capital Medical University were retrospectively analyzed, including age, gestational age of symptom first occured, LVNC history, clinical symptoms, New York Heart Association (NYHA) cardiac function class, echocardiography, blood brain natriuretic peptide (BNP), treatment and the maternal and fetal outcomes.Results:Five cases were diagnosed before pregnancy, of which there were three women with medication; one case diagnosed in the month of pregnancy; one case diagnosed at 36 weeks of gestation. NYHA cardiac function was grade Ⅰ in four cases and grade Ⅱ in three cases before or during the first trimester of pregnancy. Of the five pregnant women who underwent echocardiography, there were one case of left ventricular insufficiency, three cases of mild left ventricular dysfunction and one case of normal left ventricular function before or during the first trimester of pregnancy. Of the five pregnant women to the second and third trimester of pregnancy, there were one case of grade Ⅳ, one case of grade Ⅲ, two cases of grade Ⅱ-Ⅲ and one case of grade Ⅱ in NYHA class ; three cases of left ventricular insufficiency, two cases of normal left ventricular function by echocardiography four cases had cardiac symptoms at 15-24 weeks of gestation and were treated with medication. In four cases, blood BNP increased to 214-1 197 ng/L during pregnancy, and were 89-106 ng/L after termination of pregnancy. There were 4 cases with arrhythmia. Indications for termination of pregnancy: LVNC complicated with heart failure in two cases, LVNC complicated with decreased cardiac function and threatened preterm birth in one case, complicated with pregnancy at full term in two cases, LVNC complicated with severe pulmonary hypertension in one case, and left ventricular dysfunction in one case. Cesarean section in four cases in the third-trimester, in one case in the second-trimester, and forceps curettage in two cases were taken. Two full-term infants,two preterm infants were born without LVNC.Conclusions:Women diagnosed with LVNC and low left ventricular ejection fraction before pregnancy are more prone to decreased cardiac function during pregnancy. Carrying out pregnancy risk assessment and strengthening the multi-disciplinary team management of high risk factors in pregnancy are conducive to achieve good pregnancy outcomes.

Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Female ; Humans ; Killer Cells, Natural ; Pregnancy ; Pregnancy Complications

Objective:To study the risk assessment, method selection and clinical management of pregnancy termination during the first and second trimester of pregnant women with cardiovascular disease.Methods:This study focused on pregnant women with cardiovascular diseases who were admitted to Beijing Anzhen Hospital during the first and second trimester of pregnancy from January 2016 to September 2019, to summarize their clinical characteristics, reasons and methods of pregnancy termination, management and outcomes.Results:Among 167 pregnant women, 119 cases (71.3%, 119/167) were in early pregnancy and 48 cases (28.7%, 48/167) were in middle pregnancy. The reasons for termination of pregnancy were cardiovascular disease (109 cases; 65.3%, 109/167), unwanted pregnancy (54 cases; 32.3%, 54/167) and other reasons (4 cases). Vacuum aspiration was performed in 98 cases and forceps curettage was performed in 19 cases, medical abortion was performed in 2 cases in early pregnancy. There was no change in cardiac function after pregnancy termination and all survived in early pregnancy. In the second trimester, 16 cases were induced by intraamniotic injection of ethacridine, 2 cases by water balloon, 1 case by oxytocin intravenous drip, and 29 cases by hysterotomy delivery. The ratio of patients with hysterotomy delivery with cardiac function grade Ⅲ-Ⅳ was significantly higher than that in the patients with vaginal labor induction in the second trimester [79% (23/29) vs 4/19; P<0.01]; the ratio of pregnancy risk grade Ⅳ-Ⅴ was also significantly higher [100% (29/29) vs 14/19; P=0.007]. The mean length of hospital stay of patients with hysterotomy delivery was significantly longer than that in the patients with vaginal labor induction [(7.1±3.4) vs (2.4±1.8) days; P<0.01]. Cardiac function was improved in 4 patients induced by ethacridine and rapid recovery without serious complications. Cardiac function decreased in 5 cases and 1 case died on the first day after hysterotomy delivery. Conclusions:Pregnancy risk assessment should be conducted as early as possible in patients with cardiovascular disease. If it is not suitable to continue the pregnancy, terminate pregnancy as early as possible to reduce the risk. Pregnancy termination methods and analgesic methods should be selected according to different gestational age and complications. The indications for hysterotomy delivery should not be relaxed at will, so as to minimize trauma and hemodynamic changes. After the termination of pregnancy, contraceptive measures should be implemented and the next treatment plan should be guided.

Objective:To explore the mechanism of B10 cell involved in cardiomyocyte hypertrophy following myocarditis, and to develop potential therapeutic strategies.Methods:BALB/c mice infected with Coxsackie virus B3 induced viral myocarditis model. The expression of angiotensin (ANG)Ⅱ and its receptor in myocarditis mice was detected. The changes of B10 cells in the hearts of control mice and myocarditis mice were analyzed by flow cytometry. After losartan was administered to myocarditis mice, the degree of myocardial inflammation was detected by HE staining, the expression of inflammatory factors was detected by ELISA, the myocardial hypertrophy was detected by wheat germ agglutinin (WGA) staining, and the changes of B10 cells in the heart were analyzed by flow cytometry. The levels of cardiac troponin T (C-TNT) and high mobility group box 1 (HMGB1) protein in neonatal mouse cardiomyocytes treated with ANGⅡ and ANGⅡ+ IL-10 were detected. Cardiomyocytes were treated with ANGⅡ, ANGⅡ+ B10 cells, ANGⅡ+ B10 cells + IL-10 receptor antibody and ANGⅡ+ B cells to detect C-TNT protein levels, and Annexin-V/PI was used to detect the apoptosis of cardiomyocytes. Cardiomyocytes were treated with oxidized HMGB1, reduced HMGB1 and disulfide HMGB1, and C-TNT expression was detected.Results:Coxsackievirus B3 infection caused cardiac hypertrophy, high expression of ANGⅡ and its receptor, and transient increase of B10 cells in mice. Losartan treatment blocked the angiotensin receptor, reduced expansion of B10 cells. B10 cells alleviated apoptosis of cardiomyocytes and inhibited the production of HMGB1 induced by ANGⅡ patch by producing IL-10, thus alleviating viral myocarditis and cardiac hypertrophy.Conclusions:B10 cells may play an important role in myocardial protection in myocarditis.

Objective To explore the effects of cranioplasty onneurological functionin patients based on the cerebral CT perfusion technique. Methods Twenty cases of patients receiving cranioplasty were rerecorded during the study period,and they wererespectively scanned by CT perfusion within 72 hours before and 2 weeks after the cranioplasty. Meanwhile,the neurological function was evaluated by neurological function scale. Results The difference of cerebral blood flow before and after cranioplasty was statistically significant(P<0.05), whereas the difference of cerebral blood volume,transit time to the peak and mean transit time was not statistically significant(P>0.05).Correlation analysis showed that the preoperativedifference ratio of thecerebral blood infusio-nis not correlated with the neurological function score(P > 0.05). The changes of preoperative and postoperative difference rateof the cerebral blood infusionwas correlated with the functional independence measure(P < 0.05), whereas not with mini-mental state examination(P > 0.05). Conclusions The neurological function of the patients after cranioplasty may be improved.This improvement may benefit from the improvement of cerebral blood flow after cranioplasty.

Objective To summarize and analyze the methods of termination of pregnancy in the first and second trimester of pregnancy with severe cardiovascular disease. Methods A retrospective analysis of 27 cases of termination of pregnancy in the first and second trimester of pregnancy in Beijing Anzhen Hospital from January 1, 2016 to December 30, 2017. All of these pregnant women were pregnancy complicated with severe cardiovascular disease in grade Ⅴ pregnancy risk. Results (1)The age of 27 pregnant women was 22-40 years, gestational age was 6-27 weeks; cardiac function grade before induced labor was: 5 cases of grade Ⅱ, 15 cases of grade Ⅲ, 7 cases of gradeⅣ. The cardiovascular diseases included ventricular septal defect in 9 cases, simple atrial septal defect in 3 cases, patent ductus arteriosus in 2 cases, tetralogy of Fallot in 2 cases, rheumatic valvular disease in 1 case, arrhythmia-paroxysmal atrial velocity in 2 cases, cardiomyopathy in 2 cases, hypertensive cardiopathy in 2 cases, primary pulmonary hypertension in 1 case, tissue disease complicated with pulmonary hypertension 1 case, hyperthyroid heart disease in 1 case, coronary heart disease in 1 case. Among them, 21 cases were complicated with pulmonary hypertension, and 5 cases with Eisenmenger syndrome.(2)Methods of termination of pregnancy:in 27 cases, eight cases of vacuum curettage, and 2 cases of forceps curettage under general anesthesia without intubation;rivanol intraamniotic induction of labor in 1 case;and hysterotomy delivery in 16 cases (11 cases were treated with continuous epidural anesthesia, 1 case was treated with combined spinal and epidural anesthesia, 4 cases were treated with spinal anesthesia).(3)After termination of pregnancy, one patient with severe primary pulmonary hypertension at 19 weeks of gestation died on the 1st day postoperative. No significant changes in cardiac function were observed in other patients before and after termination of pregnancy, and all of them survived. Conclusions In patients with severe cardiovascular disease, termination of pregnancy after pregnancy may result in maternal death even at the second trimester of pregnancy. It is strongly recommended that such patients undergo pre-pregnancy assessment and fertility counseling. If visiting doctor after pregnancy, we should organize a multidisciplinary consultation as soon as possible to assess the risk of continuing pregnancy and give medical advice. If the risk of pregnancy is high, we should terminate the pregnancy as early as possible, after making a suitable treatment plan. During termination of pregnancy, temporary or permanent contraception may be taken if the condition permits.

Objective To evaluate the effect of electroacupuncture (EA) preconditioning on inositol-requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP1) signaling pathway in endoplasmic reticulum in the cortex in a rat model of cerebral ischemia-reperfusion (I/R).Methods One hundred and eight pathogen-free healthy male Sprague-Dawley rats,aged 8-12 weeks,weighing 200-250 g,were assigned into 3 groups (n =36 each) using a random number table:sham operation group (group S),group I/R and EA preconditioning group (group EA).Focal cerebral I/R was induced by occlusion of right middle cerebral arteries for 2 h followed by reperfusion in rats anesthetized with chloral hydrate.In group EA,Baihui acupoints were stimulated with an electric stimulator for 30 min once a day for 5 consecutive days starting from 5 days before ischemia,and the model was established at 24 h after the last preconditioning.Rats were sacrificed after neurological deficit was scored at 6,12 and 24 h of reperfusion,brains were removed,and the ischemic area in cerebral cortex was isolated for examination of the cell ultrastructure (with an electronic microscope) and for determination of the expression of IRE1 and XBP1 (by Western blot).Results Compared with group S,the neurological deficit scores were significantly increased,and the expression of IRE1 and XBP1 in the ischemic area was up-regulated at each time point in I/R and EA groups (P＜0.01).Compared with group I/R,the neurological deficit scores were significantly decreased,and the expression of IRE1 and XBP1 was up-regulated at each time point in group EA (P＜0.05).The cell damage in the ischemic area in cerebral cortex was significantly attenuated in group EA when compared with group I/R.Conclusion The mechanism by which EA preconditioning attenuates cerebral I/R injury is related to activating IRE1-XBP 1 signaling pathway and relieving endoplasmic reticulum stress in rats.