Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Purpose To investigate the predictive value of 18F-FDG PET/CT radiomic features before treatment for progression free survival(PFS)and overall survival(OS)in diffuse large B-cell lymphoma(DLBCL).Materials and Methods A total of 135 patients with pathologically proven DLBCL in Chinese PLA General Hospital from January 2016 to December 2018 and 18F-FDG PET/CT imaging prior to treatment were retrospectively collected.Patients were randomly divided into training set and test set using 8∶2,and then the training set was divided into training set and verification set using 8∶2 to construct the model.Semi-automatically delineated patients'lymphoma lesions as regions of interest and extracted the features.Univariate COX and least absolute shrinkage and selection operator regression were used to screen the features,and the non-zero radiomic features were obtained and the weight coefficients were used to calculate the Radscore value of each patient,and the predictive value of Radscore on PFS and OS was analyzed.Three models were established using traditional prognostic indicators(metabolic parameters and clinical factors),Radscore and combination.C-index,time-dependent area under the curve and decision curve were used to evaluate the model prediction efficiency.Finally,based on the optimal model,a column diagram was drawn,and the calibration curve was used to verify the efficiency of the column diagram.Results The combined model predicted PFS and OS at 3 and 5 years better than the traditional prognostic index model and Radscore model(Z=0.962 1-2.253 9,all P<0.05).Decision curve showed that the combined model achieved the greatest clinical net benefit.The calibration curve showed that the predicted values of the nomogram were in good agreement with the observed values.Conclusion Radscore is an independent prognostic factor for survival in DLBCL patients.The combined model has great application value in guiding the formulation of clinical individualized treatment plan.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

OBJECTIVE To study of the dynamic evolution process of the themes of off-label drug use from a macroscopic perspective, perspective is needed to reveal the overall development vein of the field, and discover research hot spots and development trends of the field. METHODS A total of 3 876 literatures published in Web of Science from 2012 to 2022 on the topic of off-label drug use were used to obtain three visual maps of overlapping map, systematic evolution map and strategic map by using SciMAT analysis, and these maps of each period were analyzed. RESULTS Over the past ten years, there had been an increasing in the number of publications, themes, and keywords on the off-label drug use, with research themes from the former period having a large impact on the latter period, with complex evolutionary pathways and increasing evolutionary themes. Roughly, 14 evolutionary paths were formed in 4 research directions:adolescents and children, treatment, off label use, and drug RCT. CONCLUSION The content and scope of research in the field of off-label drug use will be diversified and developed, with greater focus on pediatric drug use, psychiatric drug use, COVID-19, and guidelines will be paid more attention.

Objective:Constructing a physical fitness test index system for pregnant women to fully understand their physical fitness level and provide a reference for exercise prescription for this population.Methods:The system was established by way of literature review and Delphi survey, which was further validated on 60 pregnant women undergoing prenatal examination at Maternal and Child Health Hospital of Beijing Haidian District from November 7, 2019, to January 7, 2020. A questionnaire was used to evaluate the satisfaction of pregnant women with the process and results of the physical fitness test. The test and survey data adopted the descriptive analysis. Paired sample t test was used for statistical analysis. Results:The index system of maternal physical fitness test during pregnancy was established through three rounds of expert discussion, and consists of three first-level indexes, 11 second-level indexes, and 23 third-level indexes. All 60 subjects completed the test successfully and no complaints or discomfort were reported. There was no significant difference in the fetal heart rate before and after the test [(142.1±3.8) vs (142.1±4.5) bpm; t=－0.025, P=0.980]. The average test duration was (32.6±3.4) min, and the average load consumption was (300.1±41.2) kcal (1 kcal=4.184 kJ). The questionnaire showed that all subjects were satisfied with the test process and results. Conclusions:The index system of physical fitness test for pregnant women established in this study is scientific, practical, and safe, which is a potential evaluation tool of the physical fitness level for pregnant women.

Single arm trial ( SAT) was widely used for new drug application ( NDA) of novel anti?cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials ( RCT) . Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti?cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.

Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.

Single arm trial ( SAT) was widely used for new drug application ( NDA) of novel anti?cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials ( RCT) . Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti?cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.

Objective To retrospectively overview the malaria death cases reported in Henan Province and analyze the cause of death. Methods The data including basic information,epidemiological survey and medical records of malaria death cases in Henan Province from 2010 to 2015 were collected and analyzed. Results In the six years,a total of 14 malaria pa?tients were dead. All the death patients were adult males and imported from Africa. They had definite histories of living in malaria?epidemic areas and the symptoms of fever. Twelve patients were diagnosed as malaria after at least twice diagnoses. The average time from symptom appearing to correct diagnosis was 6.5 d. The causes of deaths were misdiagnosis and delayed treatment. Con?clusions The major reasons of malaria death cases in Henan Province are the failure of correct diagnosis and prompt treatment. Health education of malaria prevention and diagnosis and treatment training of malaria should be strengthened in order to im?prove the public awareness and the diagnosis ability of clinical doctors for malaria,which can prevent the death of imported ma?laria cases.

Objective To understand the epidemic characteristics of imported malaria in Henan Province from 2012 to 2014,so as to provide the evidence for proposing the reasonable suggestions for imported malaria prevention and control. Meth?ods The data of imported malaria were collected and the epidemic characteristics were analyzed in Henan Province from 2012 to 2014. Results A total of 569 imported malaria cases were reported in Henan Province from 2012 to 2014,including 445 cas?es of falciparum malaria,48 cases of vivax malaria,61 cases of ovale malaria,14 cases of quartan malaria,and 1 case of mixed infection. All the malaria cases were confirmed in laboratory. During the three years,the time of higher incidence was in Spring Festival,and May and June,and the cases mainly distributed in Luoyang,Zhengzhou,Puyang,Xinxiang,Anyang,Xuchang and Nanyang cities,accounting for 68.54%. Totally 82.43%of the patients were male youth and middle?aged. Of the 569 pa?tients,534(93.85%)returned from Africa and 35(6.15%)returned from Southeast Asian countries. The average time was 6.22 d and the median was 4 d from the onset to diagnosis. Among 569 cases,290(50.97%)were confirmed by different levels of cen?ters for disease prevention and control,and 279(49.03%)were diagnosed by different levels of medical institutions. Conclu?sions The imported malaria cases have been increased obviously in recent 3 years in Henan Province. Therefore,the health ed?ucation for the knowledge about malaria prevention and control,and the technician training should be strengthened.