Objective:To explore the relationship between macrophage infiltration in the coronary plaque and downstream myocardial perfusion in mice.Methods:The experimental group consisted of 20 ApoE knockout mice models of the coronary plaque established by feeding with cholesterol-rich diets, and the control group consisted of 20 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice.Adenosine stress myocardial contrast echocardiography was performed on all experimental animals to obtain the values of A, β and A×β of the left ventricular myocardium in anteroseptal and posterior walls both in the resting status and during adenosine stress. Concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using mouse enzyme-linked immunosorbent assay kits according to the manufacturer′s instructions. The degree of macrophage infiltration in the coronary plaque was evaluated by pathological immunohistochemistry staining and the correlations with the above indicators were analyzed.Results:There were no statistically significant differences in heart rate and left ventricular structural parameters between two groups (all P>0.05). The experimental group had a lower left ventricular ejection fraction( P=0.021), and higher weight and serum levels of triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, IL-6, and TNF-α than the control group (all P<0.05). The values of A, β and A × β of the left ventricular myocardium in anteroseptal and posterior walls in the experimental group were significantly lower than those in the control group during adenosine stress (all P<0.05). In the experimental group, the value of the macrophage infiltration found in the plaque of the left main coronary artery correlated positively with the level of serum TNF-α ( r=0.63, P=0.003) and negatively correlated with the values of A×β of the left ventricular myocardium in anteroseptal and posterior walls during adenosine stress ( r=-0.74, P<0.001; r=-0.72, P<0.001; respectively). Conclusions:Myocardial perfusion in ApoE knockout mice models of the coronary atherosclerosis was related with degree of macrophage infiltration in the coronary plaque, and macrophages may play a role by releasing inflammatory mediator TNF-α.

This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.

OBJECTIVE To analyze the serum chemical composition of rats after intragastric administration of water extract of crude Anemarrhenae Rhizoma-crude Phellodendri Chinensis and salted Anemarrhenae Rhizoma-salted Phellodendri Chinensis based on liquid chromatography-mass spectrometry(LC-MS)technology,predict the effect of salt processing on the treatment of type 2 dia-betes in Anemarrhenae Rhizoma-Pheellodendri Chinensis combined with network pharmacology,and preliminarily verify it through in vitro experiments.METHODS Rats were continuously intragastrically administered with crude Anemarrhenae Rhizoma-crude Phello-dendri Chinensis drug pair and salted Anemarrhenae Rhizoma-salted Phellodendri Chinensis drug pair water extract twice,with an in-terval of 1 h.After 60 min of the last administration,the blood was taken from the abdominal aorta,and the protein was precipitated by methanol.After dissolution,the chromatographic column was Shim-pack GIST C18(4.6 mm×150 mm,5 μm);the mobile phase A was 0.1%formic acid water,and the mobile phase B was 0.1%formic acid-acetonitrile;gradient elution,positive and negative ion full scan mode,mass scan range 100-1 500 m/z.Combined with the secondary spectrum of the database and literature,the blood compo-nents of crude Anemarrhenae Rhizoma-crude Phellodendri Chinensis drug pair and salted Anemarrhenae Rhizoma-salted Phellodendri Chinensis drug pair were analyzed and identified.The disease targets of type 2 diabetes were retrieved,and the protein interaction net-work analysis,GO and KEGG pathway enrichment analysis were performed on the intersection targets of blood components and diseases.The"blood components-targets"network diagram was constructed,and the selected core components and core targets were verified by molecular docking using AutoDock software.In the verification experiment,HepG2 cells were used as the experimental ob-ject,and the insulin resistance model was induced by high insulin and high glucose.CCK8 method was used to test the effect of Rhizo-ma Anemarrhenae-Phellodendri Chinensis on cell proliferation before and after salt processing.Western blot was used to detect the ex-pression of PI3K-AKT signaling pathway-related proteins.RESULTS 15 prototype components and 1 mangiferin metabolic compo-nent were identified in the serum of rats.17 prototype components and 1 mangiferin metabolite were identified in the rat serum of the water extract of Anemarrhenae Rhizoma-Phellodendri Chinensis after salt processing.The contents of mangiferin,berberine and 3-isobutylglutaric acid in the blood components after salt-processing were higher than those in the raw products.According to the results of KEGG and GO,the treatment of type 2 diabetes may be related to the transcriptional regulation of RNA polymerase,inflammatory re-sponse,AGE-RAGE,PI3K-AKT pathway and insulin resistance.Cell experiments showed that the ratio of p-PI3K/PI3K,p-AKT/AKT and GLUT4 protein expression could be up-regulated before and after salt processing,and the effect of salt processing group was better than that of the crude group.CONCLUSION This experiment preliminarily revealed the components of Anemarrhenae Rhizo-ma-Phellodendri Chinensis drug pair entering the blood before and after salt exposure,and suggested that ferulic acid,berberine,ber-berrubine,mangiferin,mTOR,SIRT1,EGFR and PPARA may be the main components and targets of Rhizoma Anemarrhenae-Phel-lodendri Chinensis after salt processing to enhance the therapeutic effect of type 2 diabetes.The mechanism may be to enhance the role of PI3K-AKT and other related signaling pathways,providing an important reference for the pharmacodynamic material basis and clini-cal application of Anemarrhenae Rhizoma-Phellodendri Chinensis before and after salt processing.

Objective:To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer(IVF-ET)with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility.Methods:A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center,Sir Run Run Shaw Hospital from April 2018 to April 2022.After applying the propensity score matching(PSM),473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study,and the pregnancy and neonatal outcomes were compared between the two groups.Results:There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups(all P＞0.05).In the stratification analysis,the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group(P＜0.05),but the very early pregnancy loss rates were similar between the two groups(P＞0.05),while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group(P＜0.05).Among different age groups of women,the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to＜30 years old group than that in the 30 to＜35 years old group(both P＜0.05),but the clinical pregnancy rate was lower in the 20 to＜30 years old group than that in the 30 to＜35 years old group(P＞0.05).Additionally,the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to＜30 years age group(P＜0.05).Conclusions:There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET.Due to the shorter transfer times,less embryo freezing damage and reduced costs,fresh embryo transfer can be considered as the first choice.However,it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Cancer is the second-leading cause of death worldwide. Cancer mortality is largely caused by the absence of recognizable early signs and a poor prognosis. Therefore, developing efficient diagnostic and prognostic biomarkers is crucial to reducing the incidence of cancer and improving its prognostic accuracy. tRNA-derived fragments are a new class of non-coding RNAs with important regulatory roles in cancer biology. In this paper, the research progress of tRNA-derived fragments as biomarkers in tumorigenesis, development, and prognosis was reviewed to provide a theoretical basis for cancer diagnosis and prognostic assessment.

In recent years, antiangiogenic drugs based on VEGF and VEGFRs signaling pathway have been widely used in the treatment of malignant tumors. Apatinib is an orally bioavailable small-molecule antiangiogenic agent and can specifically inhibit the tyrosine kinase activity of VEGFR, thereby inhibiting tumor angiogenesis. Apatinib is the first-level recommendation of third-line treatment of gastric cancer in CSCO Guidelines for the Diagnosis and Treatment of Gastric Cancer published in 2018. Apatinib has been proved to be effective and safe in gastric, lung and breast cancers. In addition, the drug shows great potential in the treatment of a variety of solid tumors. This article reviews the recent progress on the mechanism, clinical efficacy, related efficacy predictors of apatinib and its combination with other antitumor drugs.

Objective:To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC).Methods:Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed.Results:(1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B 12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions:One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective:To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC).Methods:UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis.Results:The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS ( P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS ( P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients ( P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage ( P=0.009). Conclusions:The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.