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.

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: 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 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 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.

Objective To explore the hippocampal(HC)microstructural changes in patients with unilateral temporal lobe epilepsy(TLE)by neurite orientation dispersion and density imaging(NODDI).Methods The NODDI indexes of the whole HC and HC subregions of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)patients,non-HS patients and healthy controls(control group)were calculated.The differences of NODDI indexes among and within the three groups were compared,and the correlation between the difference indexes and the clinical characteristics of the patients was analyzed.Results A total of 47 patients with TLE(27 cases of TLE-HS,20 cases of non-HS)and 22 cases of healthy controls were enrolled.In the TLE-HS group,the free-water isotropic vol-ume fraction(fiso)values of the HC and granular cell layer of dentate gyrus(GC-DG)subregions of the affected side were signifi-cantly higher than those of the contralateral side;the orientation dispersion index(ODI)values of the CA1 and CA4 subregions were significantly lower than those of the contralateral side;and the neurite density index(NDI)values of the HC,CA1,CA2-3,CA4 and GC-DG subregions of the affected side decreased significantly.There was no significant difference between the affected side and the contralateral side in the non-HS group.The fiso values of the HC and GC-DG subregions of the affected side in the TLE-HS group were significantly higher than those in the control group,the ODI values of the HC CA1 subregions of the affected side in the TLE-HS group were significantly lower than those in the control group and the non-HS group,the NDI values of the HC and subiculum(Sub),CA1,CA4 and GC-DG subregions of the affected side in the TLE-HS group were significantly lower than those in the con-trol group,and the NDI values of the HC and CA1,CA4 and GC-DG subregions of the affected side in the non-HS group were significantly lower than those in the control group.In the TLE-HS group,the NDI value of the HC CA4 subregion of the affected side was negatively correlated with the disease course,but there was no clear correlation between other subregion variables and disease course,onset frequency and duration of single onset.Conclusion NODDI technique has the ability to detect the microstructural changes of HC in patients with TLE,among which NDI is more likely to highlight neuronal damage and fiber reorganization in patients with TLE.

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.

Objective:To evaluate the clinical application of urine sediment score (USS) in early diagnosis, etiological differentiation, staging and prognosis of acute kidney injury (AKI), and to investigate the diagnostic efficacy of independent USS and its combination with blood urea nitrogen(Bun) serum creatinine(sCr) and uric acid(UA) in AKI.Methods:From August 23 to September 28, 2023, 9 020 morning urine samples of hospitalized patients in the First Hospital of Jilin University were detected by Sysmex UF5000.A total of 3 226 ssamples with small and round cell (SRC) > 1/μl and/or CAST>1/μl were screened for microscopic examination, and 404 cases with positive renal tubular epithelial cells and/or cast were enrolled in this study. There were 218 males and 186 females, aged 59.5 (49.0, 71.0) years. The 404 cases were divided into the USS AKI group (345 cases) and the USS non-AKI group (59 cases) according to the USS results based on the microscopic findings. According to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, they were divided into KDIGO criteria AKI group (63 cases) and KDIGO criteria non-AKI group (341 cases), and the AKI group was divided into renal AKI group (33 cases) and non-renal AKI group (30 cases). According to the clinical diagnosis recorded in the medical records, they were divided into clinically diagnosed AKI group (29 cases) and clinically diagnosed non-AKI group (375 cases).The χ 2 test or Fisher exact test was used to compare USS in different AKI causes and stages. Logistic regression was used to calculate the odds ratio of renal AKI and stage 3 AKI. The area under the receiver operating characteristic curve was used to evaluate the sensitivity and specificity of USS, sCr, UA and Bun alone and in combination in the diagnosis of AKI, and the best cut-off value, sensitivity and specificity in the diagnosis of AKI were calculated. P < 0.05 was considered statistically significant. Results:The USS was used to identify the etiology of KDIGO standard AKI group,and there were significant differences in USS between renal AKI group and non-renal AKI group (χ 2=11.070, P<0.001). Compared to USS=1, the odds ratio of renal AKI was 8.125 when USS≥2 (95% CI 2.208—29.901). There was a statistically significant difference in the comparison of USS between groups in each stage of the AKI staging study based on USS (χ 2=15.724, P<0.05). Compared to USS=1, the odds ratio of stage 3 AKI was 9.714 when USS≥2 (95% CI 1.145-82.390). The AUC of independent USS in the diagnosis of AKI was 0.687 (95% CI 0.618-0.757, P<0.001), the specificity was 65.7% and the sensitivity was 61.9%. The AUC of USS combined with Bun, sCr, UA in the diagnosis of AKI was 0.794 (95% CI 0.608-0.980, P<0.05), the specificity was 82.4%, and the sensitivity was 88.9%. Conclusions:There wasan increased likelihood of renal AKI or stage 3 AKI while USS≥2,and whose combination with Bun, sCr and UA will improve the diagnostic efficiency of AKI.