Objective To explore the levels of γ-aminobutyric acid complex(GABA+),glutamate and glutamine(Glx)in the bilateral hippocampal region of patients with temporal lobe epilepsy(TLE),and to analyze the potential clinical correlation.Methods The levels of GABA+and Glx in the hippocampal region of 23 TLE patients(TLE group)and 20 healthy volunteers(control group)were measured by quantitative Meshcher-Garwood point resolved spectroscopy(MEGA-PRESS)sequence.The differences of metabolite levels in bilateral hippocampal region were compared.At the same time,the differences of metabolites in hippocampal region between control group,TLE affected subgroup and TLE unaffected subgroup were compared.Spearman correlation coefficient was used to evaluate the correlation between hippocampal region metabolite levels and clinical.Results The levels of two metabolites in bilateral hipp-ocampal region of the control group were symmetrical distribution.The GABA+level in the affected hippocampal region of the TLE group was significantly lower than that in the bilateral hippocampal region of the control group,and the Glx level in the affected hip-pocampal region of the TLE group was not significantly different from that of the control group.The level of GABA+in the affected hippocampal region of the TLE group was significantly lower than that of the unaffected[(1.65±0.85)i.u.vs(1.86±0.58)i.u.;(1.68±0.67)i.u.vs(1.80±0.81)i.u.];The level of GABA+in the affected hippocampal region of the TLE subgroup with cogni-tive impairment(CI)was significantly lower than that of the TLE subgroup with normal cognition,and there was no significant difference in Glx content between the two subgroups(P>0.05).The level of GABA+in the TLE subgroup with CI was negatively correlated with the course of disease and attack frequency(r=-0.90,P<0.05;r=-0.91,P<0.05).Conclusion The change of GABA+level in hippocampal region is a marker of TLE occurrence and disease progression,and is closely related to CI.

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Objective To explore the levels of γ-aminobutyric acid complex(GABA+),glutamate and glutamine(Glx)in the bilateral hippocampal region of patients with temporal lobe epilepsy(TLE),and to analyze the potential clinical correlation.Methods The levels of GABA+and Glx in the hippocampal region of 23 TLE patients(TLE group)and 20 healthy volunteers(control group)were measured by quantitative Meshcher-Garwood point resolved spectroscopy(MEGA-PRESS)sequence.The differences of metabolite levels in bilateral hippocampal region were compared.At the same time,the differences of metabolites in hippocampal region between control group,TLE affected subgroup and TLE unaffected subgroup were compared.Spearman correlation coefficient was used to evaluate the correlation between hippocampal region metabolite levels and clinical.Results The levels of two metabolites in bilateral hipp-ocampal region of the control group were symmetrical distribution.The GABA+level in the affected hippocampal region of the TLE group was significantly lower than that in the bilateral hippocampal region of the control group,and the Glx level in the affected hip-pocampal region of the TLE group was not significantly different from that of the control group.The level of GABA+in the affected hippocampal region of the TLE group was significantly lower than that of the unaffected[(1.65±0.85)i.u.vs(1.86±0.58)i.u.;(1.68±0.67)i.u.vs(1.80±0.81)i.u.];The level of GABA+in the affected hippocampal region of the TLE subgroup with cogni-tive impairment(CI)was significantly lower than that of the TLE subgroup with normal cognition,and there was no significant difference in Glx content between the two subgroups(P>0.05).The level of GABA+in the TLE subgroup with CI was negatively correlated with the course of disease and attack frequency(r=-0.90,P<0.05;r=-0.91,P<0.05).Conclusion The change of GABA+level in hippocampal region is a marker of TLE occurrence and disease progression,and is closely related to CI.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

Background: The association between high thyrotropin receptor antibody (TRAb) titers at diagnosis and long-term outcomes following prolonged antithyroid drug (ATD) therapy in Graves’ disease (GD) remains unclear. This study examined TRAb dynamics and outcomes in high-titer patients receiving prolonged ATD. Methods: In this retrospective cohort (2018–2021), 1,148 of 3,052 newly diagnosed GD patients met inclusion criteria (≥18-month ATD course, TRAb negativity before withdrawal, and ≥12-month follow-up). Initial TRAb levels were defined as low-titer (<5.25 IU/L, 3×upper normal limit [UNL]), intermediate-titer (5.25–10.5 IU/L), and high-titer (>10.5 IU/L, 6×UNL). Outcomes included TRAb dynamics, treatment duration, and relapse. Results: High-titer patients required longer therapy (50 months vs. 30 months vs. 22 months, P<0.001) and slower thyroid-stimulating hormone normalization (6 months vs. 4 months vs. 2 months, both P<0.001). TRAb negativity at 24/48 months occurred in 91.85%/99.26% (low-titer), 52.38%/75.24% (intermediate-titer), and 12.70%/52.68% (high-titer) (P<0.001). High-titer patients showed fluctuant (46.20%) or smoldering (28.89%) trends. Remission rates declined with higher TRAb titer (60.45% vs. 42.70% vs. 30.47%, P<0.001). High-titer patients showed increased risk of persistent TRAb positivity (2.17-fold; 95% confidence interval [CI], 1.55 to 3.05) and relapse (1.66-fold; 95% CI, 1.45 to 3.22). Thresholds of 10.90 IU/L and 16.01 IU/L predicted positivity and relapse, respectively. Definitive therapy post-relapse was more common in high-titer patients (38.29% vs. 16.98% in low-titer, P<0.001). Conclusion High TRAb titers strongly predict persistent TRAb positivity and relapse after ATD withdrawal. Cut-off at 10.90 and 16.01 IU/L may guide prognosis and treatment.

Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.

To investigate the role of chebulagic acid(CA)in regulating lipopolysaccharide(LPS)-in-duced inflammatory response in endometrial tissue of dairy cows,and to provide new ideas for the treatment and new drug development of endometritis in dairy cows.The endometrial tissues of dairy cows were isolated and cultured in vitro,stimulated with 1 mg/L LPS for 1 h and then co-cultured with CA(12.5,25.0,50.0,100.0 mg/L).Then the endometrial tissues of different treat-ment groups were collected for experiments.The protein secretion and gene expression levels of TNF-α,IL-6 and IL-1β were detected by ELISA and real-time fluorescence quantitative PCR.HE staining was used to observe the degree of endometrial tissue damage.The expressions of high mobility protein 1(HMGB-1)and hyaluronidase binding protein 2(HABP-2)were detected by immunofluorescence.The phosphorylation levels of ERK,p65 and IκBα were detected by Western blot.The results showed that the protein secretion levels of TNF-α at 6,24 h and IL-6 at 6,12 and 24 h,and the gene expression levels of IL-1β and IL-6 at 6,9,and 12 h and TNF-α at 6 h were sig-nificantly down-regulated after CA treatment with the LPS-induced endometrial tissue inflammation response model of dairy cows.HE staining showed that compared with the LPS group,the LPS+CA group had some improvements,the degree of epithelial cell exfoliation was reduced,the struc-ture of glands and blood vessels was relatively complete,the degree of inflammatory cell infiltra-tion was reduced,and there was no obvious necrosis or hemorrhage.The expression of HMGB-1 and HABP-2 in LPS+CA group was also significantly down-regulated.The phosphorylation levels of ERK,IκBα and p65 in the LPS+CA group were significantly decreased.In conclusion,CA can reduce LPS-induced inflammation in the endometrial tissue of dairy cows by inhibiting the activa-tion of MAPK and NF-κB pathways and down-regulating the expression of inflammatory factors in the uterine tissue.It is concluded that CA may be a potential therapeutic agent for endometritis in dairy cows and deserves further research and development.

Objective To systematically analyze the effect of virtual reality(VR)and augmented reality(AR)on cognition,emotion and adaptive behavior in children and adolescents with autism spectrum disorder(ASD). Methods The randomized controlled trials(RCT)about the effect of VR or AR interventions on cognition,emotion and adaptive behavior in children and adolescents with ASD were retrieved from databases of PubMed,Cochrane Li-brary,Embase,Web of Science,CNKI,VIP and Wanfang data from January,2008 to August,2024,and a system-atic review was conducted. Results Nine RCT from China,Italy,Spain,Iran and the United Kingdom,involving a total of 384 participants,were in-cluded,published between 2016 and 2024.Participants aged two to 15 years.The approaches included VR im-mersive headsets,Xbox 360 Kinect game consoles,CAVE-style immersive virtual environments and AR;cov-ered daily life scenario experiences,cognitive and social scenario training,and emotion recognition tasks.Out-come measures involved cognitive function,emotional function,attention,memory,basic interpersonal communi-cation and adaptive behavior.Interventions typically lasted 15 to 60 minutes a time,one to three times a week,for three to 24 weeks.VR-based training improved overall cognition,emotion recognition,emotional control and expression,basic interpersonal communication and adaptive behavior;while AR-based training improved execu-tive function,spatial orientation,task focus and memory. Conclusion VR and AR are effective on overall cognitive function,emotional function,attention,memory,basic inter-personal communication and adaptive behavior in ASD children and adolescents.

Objective To explore the value of automatic segmentation technique combined with neurite dispersion and density imaging(NODDI)for displaying volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy(mTLE-HS).Methods MRI data of 33 patients with left mTLE-HS(mTLE-HS group)and 35 healthy adults(control group)were retrospectively analyzed.The hippocampal subregions were automatically segmented using FreeSurfer software,the volume of cornu Ammonis(CA)1,CA2-3,CA4,granulose cell-dentate gyrus(GC-DG)and subiculum were measured,then the NODDI parameters of each subregion were obtained through post-processing.The intra-and inter-groups hippocampal subregion volumes and NODDI parameters were compared,and the correlations of parameters being significantly different with the onset age and disease courses were analyzed.Results The volume of hippocampal subregions in mTLE-HS group were all lower than those in control group(all P＜0.05).In mTLE-HS group,the neurite density index(NDI)of left CA1 and CA4 subregions were both lower,while the free-water isotropic volume fraction(fiso)of the left CA1 subregion was higher than those of the right side(all P＜0.05).The orientation dispersion index(ODI)of left CA1,CA2-3 and CA4 subregions,as well as NDI of left CA1,CA4 and GC-DG subregions in mTLE-HS group were all lower than those in control group(all P＜0.05),while fiso of left CA1,GC-DG and subiculum subregions in mTLE-HS group were all higher than those in control group(all P＜0.05).The volume of left hippocampal subregions in patients with mTLE-HS were all moderately positively correlated with the onset age(r=0.540-0.667,all P＜0.001)but weakly negatively correlated with disease courses(r=-0.492--0.386,all P＜0.05).NDI of left CA4 and GC-DG subregions in patients with mTLE-HS were both weakly negatively correlated with disease courses(r=-0.418,-0.388,both P＜0.05).Conclusion Automatic segmentation technique combined with NODDI could be used to display the volume and microstructure changes of mTLE-HS.NDI might be a biomarker of mTLE-HS being sensitive to progressive neuronal damage.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.