Objective To analyze the effect of luteinizing hormone (LH) change amplitude in follicular phase on ovarian response and pregnancy outcome after fresh embryo transfer cycle in infertility patients with normal ovarian function during controlled ovarian hyperstimulation (COH) with antagonist protocol. Methods A total of 277 infertility patients who underwent in vitro fertilization and embryo transfer (IVF-ET) in the Center for Reproductive Medicine of this hospital from January 2019 to December 2021 were se-lected.Patients were divided into the high LH group (n=91),medium LH group (n=93) and low LH group (n=93) according to the tertiles of changes between LH level on the fourth day of COH and basal LH level before COH administration.The basic clinical features,use of exogenous gonadotropin (Gn) during COH, hormone levels at different periods,indexes of ovarian response,laboratory outcomes and pregnancy outcomes during fresh embryo transfer cycle were compared among all groups.Results There was no significant differ-ence in age,infertility duration,infertility types,basal follicle stimulating hormone (FSH),estradiol and tes-tosterone levels among the three groups (P>0.05).The duration of use of Gn in the high LH group was the shortest,the total amount and initiation dose of Gn was the smallest,and the estradiol level,ovarian sensitivity index (OSI),numbers of oocytes,metaphase Ⅱ(MII) oocytes,diprokaryotic fertilization,embryo formation and high-quality embryos were the highest after exogenous Gn stimulation,and the differences were statisti-cally significant compared with the other two groups (P<0.016).There was no significant difference in the clinical pregnancy rate,biochemical pregnancy rate and early miscarriage rate during fresh embryo transfer cy-cle among the three groups (P>0.05).Conclusion The infertility patients with normal ovarian function who have a large decrease in LH level during COH with antagonist protocol can obtain better embryo quantity and quality,but there was no effect on the pregnancy outcome during fresh embryo transfer cycle.

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
Animals ; Sevoflurane/toxicity* ; Microglia/drug effects* ; Anesthetics, Inhalation/adverse effects* ; Mice ; Mice, Inbred C57BL ; Receptors, Erythropoietin/metabolism* ; Neuronal Plasticity/drug effects* ; Male ; Prefrontal Cortex/drug effects* ; Erythropoietin/pharmacology* ; Signal Transduction/drug effects*

Objective: To study the effect of the inhibitor of Notch signaling pathway-γ-secretase inhibitor DAPT on the ultrastructures of middle ear in the ovalbumin (OVA)-mediated allergic OME in vivo. Methods: Male Sprague-Dawley (SD) rats, weighing 250-300 g, were completely and randomly divided into three groups (5 rats, 10 ears in each group):(1)Control group(2)OME group(3)OME+DAPT group. Rats in the OME group underwent systemic and local sensitization by intraperitoneal and intratympanic injection of ovalbumin to make the model of OVA-induced OME. Rats in the control group were sensitized with PBS. On the basis of establishing the OME model, OME+DAPT group were intraperitoneal injected with DAPT (10 mg/kg) for seven consecutive days and were administered before intratympanic injection of ovalbumin. After the model was successfully established, endoscopy,H&E staining and scanning electron microscopy were used to study the histology and mucous-ciliary ultrastructures of the non-ciliated and ciliated mucosa in the middle ear of each group. One-way ANOVA and Tukey methods were used for statistical analysis. Results: H&E staining showed that the three groups had statistically significant differences in submucosal thickness both in non-ciliated and ciliated regions (non-ciliated area:(6.83±1.47)μm, (38.58±9.57)μm, (32.17±11.89)μm, respectively. F=107.9;cilia area:(26.69±3.22)μm, (30.41±6.75)μm, (26.76±4.06)μm, respectively. F=5.62,both P<0.01). The thickness of the submucosa in the non-ciliated area and the cilia area of the OME group were significantly thicker than that of control group (F=42.08 and 4.40,both P<0.05); the thickness of the non-ciliated area and the ciliated area in OME+DAPT group were reduced compared to OME group(F=1.55 and 2.77,both P<0.05). Scanning electron microscopy showed that the array of cilia on the middle ear mucosa was disorderly arranged and inversed, this phenomenon was relieved in the OME+DAPT group. The number of goblet cells in the control group, OME group, and OME+DAPT group were 9.87±1.92; 15.67±5.77; 10.33±1.99 respectively and the difference between them was statistically significant (F=11.43, P<0.01). The number of goblet cells in the OME group were significantly higher than those in the control group (F=9.00,P<0.01) and the number of goblet cells in the OME+DAPT group were decreased compared to those of OME group (F=8.41, P<0.01). Conclusions: The study demonstrates the pathological changes of the ultrastructure in middle ear in OVA-induced OME and the effect of the γ-secretase inhibitor on it. In OME group, the cilia are disorderly arranged and inversed, the number of goblet cell is increased and they are swelled which suggest the hypersecretion of the mucus. DAPT can regulate OVA-induced allergic inflammation and relieve pathological changes of ultrastructure in middle ear mucociliary transport system through alleviating submucosal inflammation, reducing the hypersecretion of goblet cell and the morphological damage of cilia through the Notch signaling pathway.
Amyloid Precursor Protein Secretases ; Animals ; Ear, Middle ; Male ; Otitis Media with Effusion/drug therapy* ; Ovalbumin ; Rats ; Rats, Sprague-Dawley

Objective Breast cancer is one of the deadliest malignancies in the world. ebracteolatain A (EA) is a kind of acetylphloroglucinol extracted from ebracteolatain. To explore the specific mechanism of EA inhibiting the proliferation of breast cancer cell MCF-7, so as to provide a new approach for the clinical treatment of breast cancer. Methods EA with different concentrations were added to breast cancer cell MCF-7 to detect changes in PKD1 protein expression. The plasmid with overexpressed PKD1 was constructed and transfected into cells, and the mRNA and protein expression levels of PKD1 were detected by real-time fluorescence quantitative PCR and Western Blot assay. CCK-8 assay was used to detect changes in cell proliferation capacity. Western Blot assay was used to detect the expression level of PKD1 and its related signaling pathways. Results EA inhibited the expression of PKD1 protein in breast cancer cells with a dose-dependent manner (P< 0.05). When transfected with the overexpressed plasmid, PKD1 was significantly increased in mRNA and protein levels (P<0.001). At the same time, PKD1 overexpression significantly reversed inhibition of EA on MCF-7 proliferation (P<0.001). It was confirmed by signaling pathway analysis that EA might affect the proliferation ability of breast cancer cells by inhibiting PKD1-mediated MEK/ERK and PI3K/AKT signaling activity (P<0.05). Conclusion EA could inhibit the proliferation of breast cancer cells by regulating PKD1-mediated MEK/ERK and PI3K/AKT signaling pathways.

Objective To preliminary investigate the clinical efficacy of whole brain simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in patients diagnosed with brain metastases ( BM) . Methods Fifty-two cases of BM admitted to our hospital from January 2016 to December 2017 were equally recruited and randomly divided into the observation and control groups. Patients in the observation group were treated with SIB-IMRT, and those in the control group received conventional whole brain radiotherapy (WBRT).The clinical efficacy and prognosis were statistically compared between two groups. Results The ORR in the observation group was 77％, significantly higher than 27％ in the control group (P=0. 00).The median survival in the observation group was 384 d,significantly longer compared with 211 d in the control group (P=0. 00).All patients in both groups successfully completed corresponding treatment. Acute adverse reactions were mainly 1-2 grade reactions. Conclusions SIB-IMRT is an efficacious and safe treatment of BM,which yields tolerable adverse events and deserves application in clinical practice.

Background:Gross target volume of primary tumor (GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ifnd a suitable cut?off value of GTV?P for prognosis prediction. Methods:Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic (ROC) curves were used to identify the cut?off values of GTV?P for the prediction of different end?points [overall survival (OS), local relapse?free survival (LRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system. Results:The 358 patients with locally advanced NPC were divided into two groups by the cut?off value of GTV?P as determined using ROC curves: 219 (61.2%) patients with GTV?P≤46.4mL and 139 (38.8%) with GTV?P>46.4mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P≤46.4mL than in those with GTV?P>46.4mL (allP<0.05). Multivariate analysis indicated that GTV?P>46.4mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriifed that the predictive ability of GTV?P was superior to that of T category (P<0.001). The cut?off values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4mL, respectively. Conclusion:In patients with locally advanced NPC, GTV?P>46.4mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.

OBJECTIVE To investigate the blocking activities of a series of potential α1-adrenoceptor (α1-AR) antagonists (Compounds B1 -B9) on α1-AR.METHODS ① A series of potential α1-adrenoceptor (α1-AR) antagonists,indolylpiperidine derivative (IPD) and Compounds B1 -B9,with indolylpiperidine moiety and different substitutes were synthesized through the coupling of indolylpiperidine and piperazine derivatives.② Inotropic responses experiment was used to examine blocking effects of IPD and Compounds B1 - B9 in isolated rat atria by phenylephrine (PE) stimulation.③ Blocking effect of IPD and Compounds B1 - B9 on phosphorylation level of extracellular signal-regulated kinase (ERK) in PE treated HEK293 cells was tested by Western blotting.RESULTS ① Potential α1-adrenoceptor (α1-AR) antagonists with indolylpiperidine moiety and different substitutes were synthesized successfully.② PE caused a dose-dependent inotropic response which was inhibited by pre-incubation of phentolamine (Phen),a non-selective α1-AR antagonist,IPD and Compounds B1,B3,B4,B7,B8 and B9,respectively; IPD and Compounds B4 and B8 caused an obvious rightward shift of inotropic response-curve,the pA2 values for IPD and Compounds B4 and B8 were 6.72 ± 0.21,6.86 ± 0.29 and 6.67 ± 0.19,respectively.③ Phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B1,B2,B3,B5,B6,B7,B8 and B9 or IPD in PE treated α1A-AR stably expressed HEK293 cells; PE-stimulated phosphorylation level of ERK1/2 was inhibited by pre-incubation with Compounds B2,B4,B7 or B8 in α1B-AR stably expressed HEK293 cells.CONCLUSION Compound B4 has a selective blocking activity on α1B-AR,and Compounds B1,B3,B5,B6 and B9 or IPD have a selective blocking activity on the phosphorylation level of ERK1/2.

In handling crises in hospitals caused by natural disasters like earthquake, systemati cpractical measures of crisis management are needed, which include: early contact with top managements for support in counter disaster supplies, immediate organization of temporary first aid stations by hospital staff, logistic support by full time personnel to solve problems such as drugs and medical equipments as well as food and drinking water, and psychological consultation to patients and staff members.