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 establish a non-invasive model for predicting axillary lymph node metastasis(ALNM)based on breast cancer related metabolic parameters.Materials and Methods A total of 158 patients diagnosed as breast cancer in Meizhou People's Hospital from January 1,2016 to March 30,2023 were selected,and all of them underwent whole-body PET/CT examination in our department before operation.Metabolic parameters of primary breast cancer[maximum standard uptake value(SUVmax),metabolic volume,total glycolysis(TLG)],highest axillary lymph node uptake SUVmax(SUVmaxALN),axillary lymph node short diameter and clinical related indexes[age,maximum tumor diameter,pathological type and tumor location]were obtained.According to the surgical and pathological results,the patients were divided into ALNM positive[ALNM(+)]group and ALNM negative[ALNM(-)]group.The relationship between the parameters of the two groups was analyzed,the best influencing factors were screened out,and binary Logistic regression was used to establish a prediction model to obtain the primary metabolic parameters of breast cancer.Results There were significant differences in TLG,metabolic volume,axillary lymph node short diameter and SUVmaxALN between ALNM(+)group and ALNM(-)group(Z=-3.924--1.812,all P<0.05),but there were no significant differences in age,tumor maximum diameter,pathological type,tumor location,primary focus SUVmax and SUVavg(all P>0.05).Multivariate Logistic regression analysis showed that TLG of breast cancer primary focus and SUVmaxALN could be used as independent risk factors of ALNM of breast cancer,and the regression model established by using these two factors was Logit(P)=0.142+0.443×SUVmaxALN-0.013×TLG.The area under the curve of ALNM prediction model based on TLG and SUVmaxALN was 0.769(95%CI 0.691-0.841,P<0.001).Conclusion TLG of breast cancer primary focus and SUVmaxALN can be used as independent predictors of ALNM of breast cancer,and the prediction model based on these two factors can predict ALNM well.This non-invasive method may have a certain application prospect in clinic.

Objective:To explore the relationship between ultrasound characteristics and invasiveness in the follicular variant of papillary thyroid carcinoma (FVPTC), and to integrate multiple ultrasound parameters for visual assessment of predictive outcomes by using Nomogram.Methods:A total of 312 FVPTC patients who were pathologically confirmed through surgery in Zhejiang Cancer Hospital and Zhejiang Provincial People′s Hospital from January 2013 to December 2023 were retrospectively collected.Based on defined criteria, FVPTC patients were categorized into high-invasion and low-invasion groups. The dataset was divided into a training set and a validation set in a ratio of 7 to 3. Clinical information and ultrasound feature parameters were collected. Univariate and multivariate Logistic regression analyses were performed on the training set. A predictive model for FVPTC invasiveness was constructed based on ultrasound features. The model′s discriminative ability and calibration were evaluated in the validation set, and a nomogram was generated.Results:The training set included a total of 218 patients with FVPTC, among which 131 were classified as high invasive.The validation set consisted of 94 patients, with 53 cases of high invasive FVPTC patients. Multivariate logistic regression analysis on the training set revealed that tumor multifocality ( OR=6.505, P=0.016), hypoechoic ( OR=3.235, P=0.103), shape ( OR=0.521, P=0.049), and microcalcifications ( OR=2.479, P=0.004) were independent influencing factors for predicting invasiveness in FVPTC. In the training set, the area under the curve (AUC) of the ultrasound predictive model was 0.704 (95% CI=0.634-0.771), and in the validation set, the AUC was 0.650 (95% CI=0.531-0.770), indicated good discriminative ability.The calibration curve showed good alignment with the ideal curve, demonstrating favorable calibration performance. Conclusions:Ultrasound features provide valuable information for assessing the invasiveness of FVPTC, and the model constructed by combining ultrasound features demonstrates good predictive efficacy for the invasiveness of FVPTC.

Abstract: Upon monitoring cytoplasmic aberrant double-stranded DNA, cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines, which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection. However, sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases, aging-associated inflammation, and neurodegenerative pathologies. Herein, we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases, with a particular review of the research and development progress of STING agonists, cGAS inhibitors, and STING inhibitors, aiming to provide some theoretical reference for the future development of cGAS-STING modulators.

Objective To investigate the effects of the rhein on the mitochondria fission and epithelial-mesenchymal transition(EMT)of breast cancer cells MDA-MB-231.Methods Human breast cancer cells were intervened with rhein,and the cells were divided into control group(0 μmol·L-1),low dose rhein group(100 μmol·L-1),and high dose rhein group(200 μmol·L-1).The proliferation activity of the cells was detected by CCK-8,and migrations was detected by Scratch-healing migration assay.The morphology and distribution of mitochondria were detected by transmission electron microscope,and the expression levels of Dynamin-related protein 1(Drp1),mitofusin2(Mfn2),E-cadherin,Vimentin proteins were detected by Western blot.Results Compared with control group,Rhein significantly reduced the protein expression of Drp1、Vimentin(P<0.05),and increased E-cadherin and Mfn2,thus down-regulating mitochondria fission,inhibiting cell proliferation and migration.High dose Rhein was better than low dose.Conclusion Rhein can inhibit the proliferation and migration of breast cancer cells by reducing the expression of Drp1,Vimentin and up-regulating Mfn2,E-cadherin proteins.

Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.
Humans ; Salmonella enterica/genetics* ; Serogroup ; Anti-Bacterial Agents/pharmacology* ; Multilocus Sequence Typing ; Cities ; London ; Clonidine ; Phylogeny ; Genomics ; Drug Resistance ; Electrophoresis, Gel, Pulsed-Field ; Microbial Sensitivity Tests

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.