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

OBJECTIVES: To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification. METHODS: C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe²⁺ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins. RESULTS: In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe²⁺ concentration and MDA level and the reduction of GP_X level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells. CONCLUSIONS The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Animals ; Phenanthrenes/toxicity* ; Ferroptosis/drug effects* ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Mice, Inbred C57BL ; Hepatocytes/metabolism* ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Iridoid Glucosides/pharmacology* ; Liver/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Male ; Amino Acid Transport System y+/metabolism*

Objective:To conduct a scoping review of research on the self-advocacy of adult cancer patients to identify their self-advocacy needs, behaviors, strengths and weaknesses, so as to provide guidance for future research in this field.Methods:Using the scoping review guidelines of Joanna Briggs Institute in Australia as a methodological framework, relevant literatures were searched in PubMed, Web of Science, Cochrane Library, Embase, Science Direct, CINAHL, Scopus, China National Knowledge Infrastructure, Wanfang, VIP and China Biology Medicine disc. The search period was from establishment of the databases to December 2023, and the results were summarized and analyzed.Results:A total of 14 articles were included, and self-advocacy needs included six types of needs, such as symptom management, communication, interpersonal support, disease information, decision-making and emotional management. Self-advocacy included four aspects, including seeking information, self-decision-making, strengthening contact with the outside world and effective communication.Conclusions:Adult cancer patients have diverse types of self-advocacy needs and certain self-advocacy behaviors. Future research should pay attention to self-advocacy needs assessment, develop corresponding tools, focus on self-advocacy behaviors, leverage the advantages of self-advocacy and explore strategies to achieve effective self-advocacy support.

Objective:To conduct a scoping review of the application of mobile health applications (MHA) in the care of patients with colorectal cancer, summarizing the development process, the functions achieved, as well as the evaluation metrics, to provide references for MHA practice and related research.Methods:Following the scoping review framework, a comprehensive search was conducted across both domestic and international databases, including the China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure (CNKI), VIP Database, Cochrane Library, PubMed, Embase, CINAHL, Web of Science, and Scopus. The search period was from the database inception to February, 2024.Results:A total of 16 studies were included. The development of MHA involved multiple methods including literature reviews, qualitative interviews, consultations with multidisciplinary teams, and guidance from theoretical models. The functions of MHA include health education, peer support, guided feedback, monitoring, and reminder features. Evaluation metrics for MHA comprise usability, adherence, and effectiveness.Conclusions:MHA has demonstrated positive effects in enhancing patients' knowledge and alleviating symptoms such as fatigue and vomiting in colorectal cancer patients. However, it is still in its early stages, and further high-quality studies are needed to scientifically develop MHA that meets patients' needs.

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model cali-bration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the thera-peutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine"disease syndrome"and"macro micro"system modeling to facilitate translational research in CHM formulas.

Objective:To investigate the mechanism of curcumin in the treatment of diabetic retinopathy (DR) by network pharmacology and molecular docking.Methods:The compounds targets of curcumin were predicted by SEA and SwissTargetPrediction databases, and the DR target genes were obtained by CTD database.The different genes were mapped and matched by Venny database to screen their intersections.The intersecting genes were submitted to GeneMANIA database to construct a protein-protein interaction network.WebGestalt database was used to conduct enrichment analysis and AutoDock Vina was used to perform molecular docking of the core targets.Results:A total of 52 targets of curcumin, 1 599 targets of DR and 48 intersecting targets were detected.The core targets were serine/threonine-protein kinase 1 (AKT1), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR), signal transduction and activator of transcription 3 (STAT3) and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Enrichment analysis suggested that these targets were mainly associated with signaling pathways, including the EGFR tyrosine kinase inhibitor resistance signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway and advanced glycosylation end product-the receptor of advanced glycosylation end product (AGE-RAGE) signaling pathway.Conclusions:Curcumin may play an important role in the treatment of DR by regulating multiple signaling pathways to inhibit the inflammatory response and combat oxidative stress.

Objective To analyze the clinicopathological features and lymph node metastases characteristics of intrahepatic cholangiocarcinoma (ICC).Methods The retrospective case-control study was conducted.The clinicopathological data of 1 321 ICC patients who were admitted to 12 hospitals from April 2007 to November 2017 were collected,including 182 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,173 in the First Affiliated Hospital of Xi'an Jiaotong University,156 in the First Hospital Affiliated to Army Medical University (Third Military Medical University),139 in the Cancer Center of Sun Yatsen University,128 in the Zhongshan Hospital of Fudan University,113 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,109 in the First Affiliated Hospital of Dalian Medical University,84 in the Tianjin Medical University Cancer Institute and Hospital,65 in the First Affiliated Hospital of Zhengzhou University,62 in the Affiliated Hospital of North Sichuan Medical College,58 in the Affiliated Drum Tower Hospital of Nanjing University Medical School and 52 in the Second Affiliated Hospital of Zhejiang University School of Medicine.Treatment planning was respectively determined by comprehensive hospitals according to clinical features and results of related examinations.Surgical procedures were performed based on the results of intraoperative examinations and patients' conditions.Observation indicators:(1) laboratory examination and treatment situations;(2) relationship between clinicopathological features and primary tumor location and diameter;(3) diagnosis of lymph node dissection and metastases;(4) relationship between clinicopathological features and lymph node metastases.Measurement data with normal distribution were represented as x±s,and comparison between groups was done by the t test.Measurement data with skewed distribution were described as M (range).Comparison of count data were analyzed using the chi-square test.Results (1) Laboratory examination and treatment situations:of 1 321 patients,cases and percentages of positive hepatitis B virus (HBV),positive serum alpha-fetoprotein (AFP) (＞ 20 μg/L),positive serum carcinoembryonic antigen (CEA) (＞ 5 μg/L),positive serum alanine transaminase (ALT) (＞75 U/L),positive serum CA19-9 (＞37 U/mL) and positive serum total bilirubin (TBil) (＞20 μmol/L) were respectively 202,80,329,207,590,300 and 15.586％ (202/1 296),7.339％(80/1 090),26.299％ (329/1 251),16.587％ (207/1 248),49.789％(590/1 185),24.000％ (300/1 250).Of 1 321 patients,1 206 underwent surgery,including 904 with hepatectomy,193 with transcatheter arterial chemoembolization (TACE),72 with percutaneous transhepatic biliary drainage (PTBD),3 with endoscopic retrograde cholangiopancreatography (ERCP),3 with PTBD + ERCP and 31 with other treatments;115 had missing registration of surgical procedures.(2) Relationship between clinicopathological features and primary tumor location and diameter:① Relationship between clinicopathological features and primary tumor location:cases with CA19-9 level ≤ 37 U/mL,38-200 U/mL and ＞ 200 U/mL were respectively 227,91,146 with primary tumor located in left liver and 282,134,137 with primary tumor located in right liver.Cases combined with hepatitis and intrahepatic bile duct stone were respectively 67,73 with primary tumor in left liver and 111,47 with primary tumor in right liver,with statistically significant differences in above indictors (x2 =6.710,5.656,12.534,P＜0.05).The results of further analysis showed that incidence age of ICC was (63± 10)years old in patients with hepatitis and (59± 10) years old in patients without hepatitis,with statistically significant differences (t =4.840,P＜0.05).② Relationship between clinicopathological features and primary tumor diameter:cases with primary tumor diameter ≤ 3 cm,with 3 cm ＜ primary tumor diameter ≤ 5 cm and with primary tumor diameter ＞ 5 cm were respectively 159,250,229 with CEA level ≤ 5 pg/L and 40,65,95 with CEA level ＞ 5 μg/L and 165,258,286 with ALT level ≤ 75 U/L and 34,57,36 with ALT level ＞ 75 U/L and 148,242,281 with TBil level ≤ 20 μmol/L and 51,73,43 with TBil level ＞ 20 μmol/L,and 37,70 and 131 patients had satellite loci of tumor,with statistically significant differences in above indictors (x2=8.669,6.637,15.129,34.746,P＜0.05).(3) Diagnosis of lymph node dissection and metastases:of 904 patients with hepatectomy,346 received lymph node dissection,total number,number in each patient and median number of lymph node dissected were respectively 1 894.0,5.5 and 4.0 (range,1.0-26.0);157 had lymph node metastases,with a rate of lymph node metastasis of 45.376％ (157/346),number and number in each patient of positive lymph node were respectively 393.0 and 2.5.Of 346 patients with lymph node dissection,114 had lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 64 with lymph node metastasis and 50 without lymph node metastasis;232 didn't have lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 93 with lymph node metastasis and 139 without lymph node metastasis.The sensitivity,specificity and diagnostic accuracy by imaging examination were respectively 40.8％,73.5％ and 58.7％.(4) Relationship between clinicopathological characteristics and lymph node metastases:lymph node metastasis rate was respectively 51.397％ (92/179) in patients with primary tumor located in left liver,39.103％ (61/156) in patients with primary tumor located in right liver,34.615％(18/52) in patients with primary tumor diameter ≤ 3 cm,42.500％(51/120) in patients with 3 cm ＜ primary tumor diameter ≤ 5 cm,52.980％(80/151) in patients with primary tumor diameter ＞ 5 cm,48.790％(121/248) in patients with CEA ≤ 5 μg/L,59.302％ (51/86) in patients with CEA ＞ 5 μg/L,40.234％ (103/256) in patients with TBil ≤ 20 μmol/L,35.106％ (33/94) in patients with TBil ＞ 20 μmol/L,with statistically significant differences in above indictors (x2 =5.078,6.262,9.456,5.156,P ＜ 0.05).Conclusions The related etiological factors may be different due to different primary location of ICC.Primary tumor in left liver is significantly associated with intrahepatic bile duct stone of left liver,and primary tumor in right liver is associated with combined hepatitis,while combined hepatitis could lead early occurrence of ICC.At present,there is a low rate of lymph node dissection in ICC patients and a high lymph node metastasis rate in patients receiving lymph node dissection.Lymph node metastasis is associated with primary tumor location and diameter,levels of CEA and TBil.Lymph node metastasis rate in left liver is higher than that in right liver,and is getting higher with increased primary tumor diameter.

Spinal cord stimulation (SCS) is a promising technique for treating disorders of consciousness (DOCs). However, differences in the spatio-temporal responsiveness of the brain under varied SCS parameters remain unclear. In this pilot study, functional near-infrared spectroscopy was used to measure the hemodynamic responses of 10 DOC patients to different SCS frequencies (5 Hz, 10 Hz, 50 Hz, 70 Hz, and 100 Hz). In the prefrontal cortex, a key area in consciousness circuits, we found significantly increased hemodynamic responses at 70 Hz and 100 Hz, and significantly different hemodynamic responses between 50 Hz and 70 Hz/100 Hz. In addition, the functional connectivity between prefrontal and occipital areas was significantly improved with SCS at 70 Hz. These results demonstrated that SCS modulates the hemodynamic responses and long-range connectivity in a frequency-specific manner (with 70 Hz apparently better), perhaps by improving the cerebral blood volume and information transmission through the reticular formation-thalamus-cortex pathway.
Adolescent ; Adult ; Brain ; physiopathology ; Consciousness ; physiology ; Consciousness Disorders ; physiopathology ; therapy ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Spinal Cord ; physiopathology ; surgery ; Spinal Cord Stimulation ; methods ; Young Adult

Objective: To understand the associations between overweight-obesity and puberty timing in children with different genders. Methods: The girls in grade 2, 3, 7, 8 and boys in grade 3, 4, 7, 8 were recruited from primary and middle schools in North new area of Shenyang, Yanqing district of Beijing, Erqi district of Zhengzhou and Jiulongpo district of Chongqing by purposive sampling method between October and December 2014, respectively. The information of demographic characteristics of the respondents were collected and the pubertal development status was evaluated by Pubertal Development Scale (PDS). A total of 6 701 students were recruited; 6 137 out of which were valid with complete questionnaires. The associations between overweight-obesity and puberty timing were estimated by multivariate logistic regression analysis. Results: The prevalence of overweight-obesity in primary schools were 34.8% (522/1 499) among boys and 24.2% (341/1 409) among girls, respectively. The prevalence of overweight-obesity in middle schools were 31.3% (591/1 658) among boys and 21.8% (342/1 571) among girls, respectively. The prevalence of premature puberty in primary schools were 15.0% (225/1 499) among boys and 14.2% (200/1 409) among girls, respectively. The prevalence of delayed puberty in middle schools were 14.3% (237/1 658) among boys and 14.9% (234/1 571) among girls, respectively. After adjusting the effects of region, age, one-child, family income and the parents' educational levels, multivariate logistic regression analysis showed that overweight-obesity had significantly positive association with premature puberty (OR=2.16, 95%CI: 1.56-2.99) among girls in primary schools, and significantly negative association with delayed puberty (OR=0.54, 95%CI: 0.36-0.80) among girls in middle schools when compared with students with normal weights, both P values were <0.05. There was no significant associations among boys in primary and middle schools between overweight-obesity and puberty timing, and the corresponding OR(95%CI) were 1.08(0.80-1.45) and 0.93(0.69-1.27) respectively, both P values >0.05. Conclusion There was significantly positive association between overweight-obesity and premature puberty among girls, and significantly negative association with delayed puberty among girls in middle schools; but the association was not found among boys.

Objective To investigate the epidemic factors of human brucellosis in Qiqihar from 2008 to 2014 so as to provide a scientific basis for prevention and control of the disease.Methods Descriptive epidemiologic method was used to analyze the monitoring results of human brucellosis in Qiqihar between 2008 and 2014.Indexes observed were:the incidence rate,the distribution of gender,age,occupation,area and time.Results From 2008 to 2014,there were a total of 15 003 cases of brucellosis covering all counties.The average incidence rate was 38.85/100 000.The average incidence rate of Meilisi Daur District was the highest,178.93/100 000.Cases occurred year around and peaked in March-July.The average incidence rate of male and female brucellosis was 57.53/100 000 and 19.35/100 000,respectively,and male patients were more than female (x2 =3 658.973,P ＜ 0.05).Most patients were in the 41-50 years old age group,and the number of patients was 4 386.The major occupation was farmer (herdsmen),which acount for 93.96％ (14 097/15 003).Conclusions Qiqihar is the epidemic area of brucellosis and has a higher incidence.Governments should pay nore attention to the epidemic of brucellosis.Health education and intervention measure for high-risk population should be strengthened and the professional team should be reinforced so as to reduce the incidence of brucellosis.