Objective: To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells. Methods: Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1. Results: 5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01). Conclusion JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.

Objective: To investigate the feasibility of magnetic anastomosis for uretero-ileal anastomosis using experimental rabbit models. Methods: Six experimental rabbits were used as the models.The lower part of the left ureter was cut with scissors，the daughter magnet (DM) was placed in the middle of the ureter，and the distal end of the ureter was ligated.After that，the ileum wall was opened，the parent magnet (PM) was inserted through it，the positions of the PM and DM were adjusted so that their ends were attracted to each other，and then ileum wall incision was sutured.The operation time，intraoperative blood loss，postoperative complications and magnet discharge time were recorded.Two weeks after operation，left ureterography was performed to obtain the specimens of the uretero-ileal anastomosis，and to observe the patency of the anastomosis.The formation of the anastomosis was observed with naked eyes and light microscope. Results: Uretero-ileal magnetic anastomosis was performed successfully in 6 experimental rabbits.The operation time was 28-39（32.50±3.94） min，and the intraoperative blood loss was less than 5 mL.The rabbits recovered well after operation，and no complications were observed.All animals survived to the end point of observation.The disconnection time of magnet after operation was 9-13(10.83±1.72) days.The gross specimen showed that the anastomosis was patent.The histological observation showed that the mucosa of the anastomosis was continuous and smooth，and the anastomosis was well formed. Conclusion: Magnetic anastomosis is feasible for uretero-ileal anastomosis with simple operation and good anastomosis formation.After further experimental verification，this technique is expected to be used in clinical practice.

OBJECTIVE: To observe the clinical efficacy of acupuncture based on the "head qijie" theory combined with endovascular intervention in the treatment of ischemic stroke (IS). METHODS: Sixty-six IS patients were randomly divided into an experimental group (33 cases, 3 cases dropped out) and a control group (33 cases, 3 cases dropped out). The control group received endovascular intervention. On the basis of the treatment in the control group, the experimental group received acupuncture based on the "head qijie" theory starting from the second day after surgery, Baihui (GV20) and bilateral Fengchi (GB20), Tianzhu (BL10), etc. were selected, once a day, 6 times a week for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and modified Rankin scale (mRS) were observed in the two groups, the clinical efficacy and safety were evaluated. RESULTS: After treatment, the NIHSS and mRS scores were decreased compared with those before treatment in both groups (P<0.01), the NIHSS and mRS scores in the experimental group were lower than those in the control group (P<0.05). After treatment, the MBI scores were increased compared with those before treatment in both groups (P<0.01), the MBI score in the experimental group was higher than that in the control group (P<0.05). The total effective rate in the experimental group was 86.7% (26/30), which was higher than 66.7% (20/30) in the control group (P<0.05). The incidence of adverse events in the experimental group was 6.7% (2/30), which was lower than 13.3% (4/30) in the control group (P<0.05). CONCLUSION Acupuncture based on the "head qijie" theory combined with endovascular intervention in treating IS has good efficacy, improves neurological function, and enhances daily living ability.
Humans ; Male ; Female ; Acupuncture Therapy ; Middle Aged ; Aged ; Ischemic Stroke/therapy* ; Acupuncture Points ; Endovascular Procedures ; Treatment Outcome ; Adult ; Combined Modality Therapy

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

Objective To explore the value of 11C-methionine(MET)PET/CT radiomics model for evaluating isocitrate dehydrogenase1(IDH1)status of glioblastoma.Methods Data of 157 patients with glioblastoma who underwent 11C-MET PET/CT examination,including 68 cases of IDH1 mutation and 89 cases of IDH1 wild-type were retrospectively analyzed.The patients were divided into training set(n=125)and validation set(n=32)at the ratio of 8:2.Based on PET/CT images,lesions ROI were delineated and radiomics features were extracted and screened to establish radiomics models with logistic regression(LR),support vector machine(SVM)and decision trees(DT),respectively.Meanwhile,the nomogram based on patients'age and radiomics features was drawn.The efficacy of radiomics models and clinical-radiomics nomogram for evaluating IDH1 status were comparatively observed.Results The area under the curve(AUC)of DT radiomics model for evaluating IDH1 status of glioblastoma in training set was 0.910,higher than that of LR(0.697)and SVM(0.698)models(both P＜0.05).In validation set,the AUC of DT model for evaluating IDH1 status of glioblastoma was 0.805,which was higher than that of LR model(0.740)and clinical-radiomics nomogram(0.704)(both P＜0.05).Conclusion 11C-MET PET/CT radiomics model based on DT was helpful for evaluating IDH1 status of glioblastoma.

Objective:To assess the correlation and consistency of electrochemiluminescence and direct chemiluminescence in detecting 12 tumor markers.Methods:A total of 2426 serum specimens were selected from the physical examination in Beijing Tiantan Hospital,Capital Medical University from March to August 2023.These specimens included 446 cases for alpha fetoprotein(AFP),284 cases for carcinoembryonic antigen(CEA),289 cases for carbohydrate antigen 72-4(CA72-4),87 cases for carbohydrate antigen 19-9(CA19-9),205 cases for carbohydrate antigen 125(CA-125),216 cases for carbohydrate antigen 15-3(CA 15-3),292 cases for total prostate specific antigen(TPSA),292 cases for free prostate specific antigen(FPSA),84 cases for serum cytokeratin 19 fragment(Cyfra21-1),84 cases for neuron specific enolase(NSE),84 cases for squamous cell carcinoma associated antigen(SCC)and 63 cases for pro-gastrin-releasing peptide(PROGrp).The electrochemiluminescence and direct chemiluminescence methods were respectively used to detect the above 12 indexes,and then,the correlation and consistency between the two detection methods were analyzed.Results:The results of Pearson and Spearman correlation analysis showed that there were significantly positive correlations between electrochemiluminescence and direct chemiluminescence methods in detecting 12 tumor indexes(AFP,CEA,CA72-4,CA19-9,CA125,CA15-3,TPSA,FPSA,Cyfra21-1,NSE,SCC and PROGrp)(r=0.971,0.934,0.945,0.975,0.900,0.948,0.994,0.984,0.982,0.828,0.879,0.922,P<0.05),respectively.The total coincidence rates between the two methods were respectively 98.21%,98.24%,98.27%,98.85%,97.07%,99.54%,99.66%,99.32%,92.86%,92.86%,95.24%and 96.83%.There were consistencies between electrochemiluminescence and direct chemiluminescence methods for 10 indexes excepted CA15-3 and NSE that could not calculate Kappa values due to data reasons(Kappa=0.848,0.728,0.930,0.794,0.485,0.887,0.664,0.540,0.477,0.652,P<0.05),respectively.Conclusion:In the detections of electrochemiluminescence and direct chemiluminescence methods for tumor indexes,there are favorable correlations and consistencies between them in detecting AFP,CA72-4,CA19-9 and TPSA,and there are favorable correlations between them in detecting CEA,CA125,FPSA,Cyfra21-1,SCC and PROGrp but the consistencies between them are average in detecting these indexes,and there are favorable correlations between them in detecting CA15-3 and NSE.Clinical detection should pay attention to there may be differences in the results between different detection methods when the detection is conducted in reference laboratory.

Objective:To investigate the effects of apolipoprotein E (APOE) ε4 allele on β-amyloid (Aβ) deposition in subcortical structures and functional connectivity (FC) between brain regions in patients with Alzheimer′s disease (AD). Methods:Forty-three patients with probable mild/moderate AD were prospectively enrolled from the First Medical Centre, Chinese PLA General Hospital between January 2023 and October 2023, including 23 APOE ε4+ patients (12 males and 11 females, age (74.8±8.4) years), 20 APOE ε4- patients (14 males and 6 females, age (77.6±8.9) years) and 20 normal cognitive volunteers (NC) (15 males and 5 females, age (75.3±6.2) years). All subjects underwent 11C-Pittsburgh compound B (PIB) PET/MR brain imaging. The differences of gray matter volume (GMV) in subcortical structures (hippocampus, amygdala) among the three groups were analyzed by one-way analysis of variance and least significant difference (LSD) t test. Independent-sample t test and Pearson correlation analysis were used to analyze difference in Aβ deposition between APOE ε4+ patients and APOE ε4- patients, and the correlation between subcortical structure and brain FC. Results:The GMV of bilateral amygdala between NC group and APOE ε4+ gene carrier group, and between APOE ε4+ and APOE ε4- gene carrier groups were significantly different ( F=6.43, P=0.002; P values: 0.002, 0.003). Significant difference of GMV was observed in the bilateral hippocampus among three groups ( F=5.34, P=0.030). Abnormal PIB uptake was detected in both the hippocampus and amygdala of both APOE ε4+ and APOE ε4- gene carrier groups, with a more pronounced effect observed in the APOE ε4+ group ( t values: 3.14, 2.19, P values: 0.032, 0.009). Taking the hippocampus as the seed point, there was no obvious abnormality in the whole brain connectivity map among APOE ε4+, APOE ε4- carriers and NC groups. With the amygdala as the seed point, the whole brain connectivity in the APOE ε4+ gene carrier group was significantly reduced, and the connectivity between the amygdala and the cingulate gyrus, parietal lobe and temporal lobe was significantly reduced in the APOE ε4+ gene carrier group compared with NC group, while the connectivity between the amygdala and the whole brain was not significantly reduced in the APOE ε4- gene carrier group. Aβ deposition in amygdala was positively correlated with FC coefficients of frontal brain regions, gyrus rectus, right middle occipital gyrus and left temporal lobe ( r values: 0.56-0.70, all P<0.05). Conclusion:APOE influences GMV and Aβ deposition of hippocampus and amygdala, and FC of amygdala, and may be involved in the pathological mechanism of cognitive impairment.

Objective:To investigate the epidemiology features, intervention effects and influencing factors of thrombosis in arteriovenous graft (AVG), and to provide reference for optimizing vascular access scheme in hemodialysis patients.Methods:It was a retrospective study. The clinical and follow-up data of patients with AVG constructed in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were analyzed. According to whether AVG thrombosis occurred during the follow-up period, they were divided into thrombosis group and non-thrombosis group, and the epidemiology status, influencing factors and patency rates of AVG thrombosis were analyzed. AVG was followed up until June 30, 2023 or abandonment or death of patient or loss of follow-up. Kaplan-Meier method was used to analyze the patency rates of AVG. Log-rank test was used to compare the differences of patency rates between groups. Logistic regression model was used to analyze the influencing factors of AVG thrombosis.Results:The study included 475 AVG from 464 patients, with age of (55.50 ± 11.85) years old, 193 males (40.6%), 185 diabetes patients (38.9%) and dialysis age of 24 (1, 68) months. One hundred and fifty-four AVG (32.4%) had a total of 307 AVG thrombotic events during the follow-up of 602 (380, 920) days, with a standardized incidence of 0.34 times per patient-year. Among them, 60 cases (19.5%, 60/307) had frequent thrombosis. Kaplan-Meier survival analysis showed that AVG secondary patency rates at 2-years and 3-years in the thrombosis group and frequent thrombosis subgroup were inferior to those in the non-thrombosis group (84.0% vs. 92.5%, P=0.017; 66.5% vs. 85.7%, P<0.001; 78.9% vs. 92.5%, P=0.030; 54.6% vs. 85.7%, P<0.001). Two hundred and sixty-nine AVG thrombotic events were analyzed to evaluate the treatment effects. Endovascular interventional surgery was used for thrombectomy in 215 cases (79.9%), and hybrid surgery (endovascular interventional surgery combined with surgical incision) was used in 54 cases (20.1%), with a technical success rate of 98.9% (266/269) and a clinical success rate of 98.1% (264/269). Kaplan-Meier survival analysis showed that there were no statistically significant differences in the primary post-intervention patency rates at 90 days and 365 days, respectively (all P>0.05), and there was statistically significant difference in the primary post-intervention patency rate at 180 days (45.1% vs. 26.5%, Z=2.563, P=0.015). Multivariate logistic regression analysis showed that graft-applied type (intering as the reference, propaten OR=1.953, 95% CI 1.139-3.350, P=0.015; acuseal OR=2.628, 95% CI 1.438-4.800, P=0.002), body mass index < 18.5 kg/m 2 (18.5-24.0 kg/m 2 as the reference, OR=0.291,95% CI 0.090-0.943, P=0.040), serum albumin < 40 g/L ( OR=1.579, 95% CI 1.019-2.445, P=0.041), serum ferritin < 200 μg/L ( OR=1.818, 95% CI 1.162-2.845, P=0.009) and mean arterial pressure < 70 mmHg ( OR=7.180, 95% CI 1.339-38.501, P=0.021) were the independent influencing factors of AVG thrombosis. Conclusions:The incidence of AVG thrombotic events is 0.34 times per patient-year, mainly concentrated in a small number of patients. Thrombosis reduces the secondary patency rate of AVG. AVG thrombosis treatment with endovascular interventional surgery or hybrid surgery has a high technical success rate and a clinical success rate. The thrombosis is related to graft-applied types, nutritional status of patients and mean arterial pressure level.

OBJECTIVE To evaluate the short-term efficacy of single-session microwave ablation for benign thyroid nodule.METHODS Patients with benign thyroid nodules treated by microwave ablation between June 2019 and December 2022 at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,were included for analysis.Thyroid function was tested 1 month after treatment,and ultrasound and thyroid function were performed 3 months,6 months and 1 year after treatment.Volume reduction rates(VRR)of nodules were calculated.Data of the last follow-up within 1 year were included for analysis.Variables including gender,age,whether Hashimoto's thyroiditis was present,longitudinal diameter of nodules,solid volume of nodules were included for univariate and multivariate analysis.RESULTS A total of 151 patients with 163 nodules were included.The perioperative complication rate was 1.99%(3/151).The VRR at half year after treatment was(79.58±17.70)%,and the success rate at half year after treatment was 93.43%(128/137).The VRR of at 1year after treatment was(81.24±24.29)%.The 1-year treatment success rate was 92.77%(77/83).Univariate and multivariate analysis showed that nodular solid volume and age were independent factors affecting VRR after ablation.Regression coefficient of age and solid volume was 0.34(P<0.05)and-0.47(P<0.05),respectively.For every 1 cm3 increase in solid volume,1-year VRR(%)decreased by 0.47.Regression equation:1-year VRR=68.92+0.34×age-0.47×solid volume.Serum FT4 gradually decreased and the thyroid stimulating hormone(TSH)gradually increased within 6 months after ablation,and the differences were statistically significant(P<0.05).After 6 months,serum FT4 gradually recovered to the normal level and TSH gradually recovered.However,TSH still did not reach the preoperative level one year after ablation.FT3 decreased gradually after treatment,but there was no significant difference between the values at each time point(P=0.40).After the ablation of thyroid nodule,the mean value of thyroid function index fluctuated,but all of them were within the normal reference range.CONCLUSION Microwave ablation is a safe and effective treatment method for benign thyroid nodules,with an overall success rate of over 90%.Solid nodule volume and age are independent factors affecting the microwave ablation effect of benign thyroid nodules.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.