Objective To investigate the effect of letrozole in decreasing the early-stage ovarian hyperstimulation syndrome (OHSS) occurrence during the luteal phase for patients of OHSS high-risk after oocyte retrieval.Methods A total of 176 high-risk OHSS patients were randomly divided into two groups after oocyte retrieval.Patients in experiment group (n=86) received 5 mg letrozole per day from the retrieval day and last for 5 days.Others in control group (n=90) received placebo.The serum concentration of FSH,LH,estradiol (E2),progesterone (P) and vascular endothelial growth factor (VEGF) from the day of hCG injection to days after injection (5 days,8 days,10 days) were measured.And the incidence of moderate and severe OHSS was observed.Results The concentration of E2 on the indicated days (5 days,8 days,10 days after hCG injection) in experiment group and control group were (5 727±2 089) versus (11 826±4 281) pmol/L,(1 613±879) versus (7 925±3 507) pmol/L,(193±90) versus (1 628±888) pmol/L; the concentration of VEGF on the indicated days in the two groups were (80± 14) versus (108± 19) ng/L,(66± 11) versus (126± 14) ng/L,(48±7) versus (148± 14) ng/L; the concentration of E2 and VEGF were lower than those in control group (all P＜0.01).The FSH concentration in experiment group were (2.1 ± 1.1) and (3.5± 1.3) U/L on the day of fifth and eighth day after hCG injection,which were significantly higher than (0.7±0.3) and (0.7±0.4) U/L in control group (P＜0.05); the LH concentration in experiment group were (0.26±0.19) and (0.72±0.60) U/L on the day of fifth and eighth day after hCG injection,which were significantly higher than (0.11 ±0.03) and (0.14±0.08) U/L in control group (P＜0.05).The incidence of moderate and severe OHSS was signicantly decreased after letrozole treatment compared with control group [2％ (2/86) versus 12％ (1 1/90),P＜0.05].Conclusion Administration of 5 mg/d letrozole for 5 days during the luteal phase can reduce the E2 and VEGF levels for the high-risk OHSS patients who needed cryopreserve all embryos,and also reduce the occurrence of early OHSS.

ObjectiveTo analyze the expression of osteopontin (OPN) and interleukin-17 (IL-17)and study the roles in the pathogenesis of chronic severe hepatitis B.MethodsTwenty patients of acute on chronic liver failure were collected from the infection disease in-patients department of the First Affiliated Hospital of Medical College,Zhejiang University from 2009 to 2010,and 40 health controls were from medical examination center during the same period.Meanwhile,Balb/C mice were used for ConA injection to induce fulminant hepatitis and the plasma,serum and liver tissue of mice were collected.OPN and IL-17concentrations were measured using ELISA kits.PBMC were separated and cultured with anti-TNF-α or TNF-α.Supernatants were collected for analysis of OPN and IL-17.Differences between groups were evaluated by using a Student's t test and the relationship between IL-17 and OPN were evaluated by Pearson correlation.ResultsIn chronic severe hepatitis B group,levels of OPN and IL-17 were markedly higher than those of healthy control,respectively.(42.4 ± 12.9 vs 10.6 ±4.8 pg/ml; 1460.1 ±523.1 vs 472.8 ±67.5 ng/ml) ( t =2.387,3.570,P ＜ 0.05).The level of OPN in blood and liver reached peak at 6 hours at 12 hours after ConA injection,respectively.The level of IL-17 in blood and liver was significantly increased after ConA injection.IL-17 were positive correlated with OPN levels (R2 =0.582,P =0.026).TNF-α can increase the level of OPN secreted by lymphocytes.ConclusionsOPN and IL-17 levels in peripheral blood of hepatitis B patients are closely related to the hepatitis B degree.TNF-α can increase the level of OPN secreted by lymphocytes.

Objective: To compare the preoperative and postoperative dosimetric parameters in the treatment of spinal metastasis, and to verify the accuracy of 3D-printing non-coplanar template (3D-PNCT) combined with CT-guided ¹²⁵I seed implantation for the treatment of spinal metastasis. Methods: The treatment plans of 7 patients with spinal metastasis (9 lesions) from 2016 to 2018 receiving 3D-PNCT in combination with CT-guided ¹²⁵I seed implantation were retrospectively analyzed. The dosimetric parameters including homogeneity index (HI), conformal index (CI), external index (EI), dose of 90% target volume(D₉₀), mPD, volume percent of 100%, 150%, and 200% prescribed dose V₁₀₀、V₁₅₀、V₂₀₀ and D_2cm³ of spinal cord were compared before and after operation. The british columbia cancer ageny particle implantation quality evaluation standard was applied to evaluate the quality of implantation. Results: The HI, EI and CI, D₉₀, mPD, V₁₀₀, V₁₅₀, V₂₀₀ and D_2cm³ of spinal cord did not significantly differ before and after the plan (all P>0.05). Five were evaluated as excellent and 4 were assessed as good. Conclusion The postoperative dosimetric parameters of 3D-PNCT combined with CT guided ¹²⁵I seed implantation of spinal metastasis are basically consistent with preoperative dosimetric parameters. The postoperative plans are evaluated as excellent or good, suggesting that the technology has a good therapeutic accuracy in the treatment of spinal metastasis.

Objective To investigate the characteristics of brain network based on brain electrical activity induced by somatosensory electrical stimulation,and to provide a theoretical basis for further understanding the mechanism of brain neural plasticity induced by somatosensory electrical stimulation.Methods Ten healthy subjects were selected and a somatosensory electrical stimulation experiment was constructed based on the directed transfer function (DTF).In the experiment,the DTF causal connection matrixes of the 32-channel EEG data of Delta,Theta,Alpha and Beta bands were obtained under the somatosensory electrical target and non-target stimulation,and the differences of clustering coefficient and global efficiency between two stimulation states were contrasted based on graph theory.Results Under the target stimulation and non-target stimulation states,the regions with stronger DTA causal connections were mainly concentrated in FCz,Cz,CPz and Pz channels.The causal connection intensity under target stimulation state was greater than that of non-target stimulation.Also,in the Delta,Theta,and Alpha bands,the clustering coefficient under the target stimulation state was significantly higher than that in the non-target stimulation state (P＜0.05).In the Delta and Theta bands,the global efficiency of the target stimulation state was significantly higher than that of the non-target stimulation state (P＜0.05).Conclusions Somatosensory electrical stimulation can activate and induce EEG brain networks.In the target stimulation state,the role of the parietal lobe in the EEG causal network is enhanced,which helps to induce attention to specific brain region plasticity,and thus realizing the nerve rehabilitation in the brain regions of interest.While in the non-target stimulation state,the synergistic interactions between brain regions were enhanced,which helps to activate and induce a wide range of associations in the whole brain network,so as to promote the global neural activity in the brain.

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

OBJECTIVE: To quantitatively assess cardiac functions in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance-feature tracking (CMR-FT) technique and evaluate the prognostic value of CMR-FT in patients with CA. METHODS: We retrospectively collected the data from 31 CA patients with systemic amyloidosis confirmed by Congo red staining and serum immunohistochemistry after extracardiac tissue biopsy undergoing CMR at our hospital from March, 2013 to June, 2021.Thirty-one age and gender matched patients with asymmetric left ventricular wall hypertrophy and 31 healthy individuals without organic or functional heart disease served as the controls.Radial, circumferential and longitudinal strains and strain rates of the left ventricle at the global level and in each myocardial segment (basal, middle and apical) were obtained with CMR-FT technique and compared among the 3 groups.The predictive value of myocardial strains and strain rates for all-cause mortality in CA patients was analyzed using a stepwise COX regression model. RESULTS: The left ventricular volume, myocardial mass, ejection fraction and cardiac output differed significantly among the groups (P < 0.05).Except for apical longitudinal strain, the global and segmental strains were all significantly lower in CA group than in HCM group (P < 0.05).The global and segmental strains were all significantly lower in CA group than in the healthy individuals (P < 0.05).The basal strain rates in the 3 directions were significantly lower in CA group than in the healthy individuals (P < 0.05), but the difference in apical strain rates was not statistically significant between the two groups.Multivariate stepwise COX analysis showed that troponin T (HR=1.05, 95%CI: 1.01-1.10, P=0.017) and middle peak diastolic circumferential strain rate (HR=6.87, 95%CI: 1.52-31.06, P=0.012) were strong predictors of death in CA patients. CONCLUSION Strain and strain rate parameters derived from CMR-FT based on cine sequences are new noninvasive imaging markers for assessing cardiac impairment in CA and cardiac function changes in HCM, and provide independent predictive information for all-cause mortality in CA patients.
Humans ; Retrospective Studies ; Magnetic Resonance Imaging, Cine/methods* ; Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Ventricular Function, Left ; Stroke Volume ; Amyloidosis/diagnostic imaging* ; Magnetic Resonance Spectroscopy ; Prognosis ; Predictive Value of Tests

Objective:To understand the profile type of serum Epstein-Barr virus (EBV) antibodies in children with infectious mononucleosis (IM), and to analyze the significance of viral capsid antigen (VCA) IgG antibody affinity in the diagnosis of IM.Methods:Retrospective analysis was performed on the results of the serum anti-EBV antibody profile and plasma EBV nucleic acid test of 150 hospitalized children with IM diagnosed in Beijing Children′s Hospital, Capital Medical University, from May 2016 to May 2019.Anti-EBV antibody profiles, including anti-VCA-IgG, anti-VCA-IgM, anti-early antigen (EA) IgA, anti-EBV nuclear antigen (EBNA) IgG, and anti-VCA-IgG affinity, were detected by enzyme-linked immunosorbent assay (ELISA). Plasma EBV nucleic acids were detected by real-time quantitative PCR.Results:There were mainly two types of anti-EBV antibody profiles in 150 children with IM: (1)130 cases who were positive for anti-VCA-IgM/IgG, negative for anti-EBNA-IgG and positive for anti-VCA-IgG antibodies with low affinity, accounting for 86.7% (130/150 cases), of which 50 cases were positive for anti-early antigen IgA; (2)18 cases who were negative for anti-VCA-IgM, positive for anti-VCA-IgG, negative for anti-EBNA-IgG and positive for anti-VCA-IgG antibody with low affinity, accounting for 12.0% (18/150 cases), of which 5 cases were positive for anti-EA IgA.EBV DNA was measured in 132 children, with a posi-tive rate of 37.9% (50/132 cases).Conclusions:There were several types of serum EBV antibody profiles in children with IM, 12.0% of patients with IM in this study were negative for anti-VCA-IgM, and the diagnosis of IM was confirmed by the affinity of anti-VCA IgG.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.