Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Objective:To evaluate alterations in dopaminergic neurons, cortical metabolism, and functional connectivity networks in patients with early-onset Parkinson′s disease (EOPD) using multimodal neuroimaging.Methods:In this prospective cross-sectional study, 26 patients with EOPD and 16 healthy controls (HC group) were recruited from the PLA General Hospital between April and November 2023. All participants underwent integrated 11C-β-CFT PET/MR, 18F-FDG PET/CT brain imaging and resting-state functional MRI. Clinical assessments were conducted using the Unified Parkinson′s Disease Rating Scale and Hoehn-Yahr staging. Cognitive status was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment. Standardized uptake value ratios for both 11C-β-CFT and 18F-FDG PET images were calculated using cerebellar gray matter as the reference region. Voxel-wise two-sample t-tests were performed to identify regions with significant group differences in tracer uptake. Seed regions showing altered 11C-β-CFT or 18F-FDG uptake were used to compute seed-based functional connectivity (FC) with all other brain voxels, and group differences in FC were assessed. Correlations between imaging metrics and clinical scales were evaluated using Pearson or Spearman analyses as appropriate. Results:Compared with HC group, EOPD group showed significantly reduced 11C-β-CFT uptake in the bilateral putamen, globus pallidus, and left temporal pole ( P<0.05), and decreased 18F-FDG uptake in the right superior frontal gyrus and anterior cingulate cortex ( P<0.05). Relative to HC group, EOPD group exhibited markedly lower FC between the right putamen and the left gyrus rectus as well as the right parahippocampal gyrus; the right superior frontal gyrus and the left gyrus rectus; the anterior cingulate cortex and the olfactory area of the frontal lobe, the left gyrus rectus, and the right superior parietal gyrus; the left temporal pole and the left orbitofrontal cortex as well as the left olfactory area ( P<0.05). Correlation analyses revealed no statistically significant associations between altered FC values and clinical scale scores in the EOPD group. Conclusions:Patients with EOPD demonstrate impaired nigrostriatal dopaminergic function, regional cortical hypometabolism, and aberrant functional connectivity across multiple brain networks.

Objective:To evaluate alterations in dopaminergic neurons, cortical metabolism, and functional connectivity networks in patients with early-onset Parkinson′s disease (EOPD) using multimodal neuroimaging.Methods:In this prospective cross-sectional study, 26 patients with EOPD and 16 healthy controls (HC group) were recruited from the PLA General Hospital between April and November 2023. All participants underwent integrated 11C-β-CFT PET/MR, 18F-FDG PET/CT brain imaging and resting-state functional MRI. Clinical assessments were conducted using the Unified Parkinson′s Disease Rating Scale and Hoehn-Yahr staging. Cognitive status was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment. Standardized uptake value ratios for both 11C-β-CFT and 18F-FDG PET images were calculated using cerebellar gray matter as the reference region. Voxel-wise two-sample t-tests were performed to identify regions with significant group differences in tracer uptake. Seed regions showing altered 11C-β-CFT or 18F-FDG uptake were used to compute seed-based functional connectivity (FC) with all other brain voxels, and group differences in FC were assessed. Correlations between imaging metrics and clinical scales were evaluated using Pearson or Spearman analyses as appropriate. Results:Compared with HC group, EOPD group showed significantly reduced 11C-β-CFT uptake in the bilateral putamen, globus pallidus, and left temporal pole ( P<0.05), and decreased 18F-FDG uptake in the right superior frontal gyrus and anterior cingulate cortex ( P<0.05). Relative to HC group, EOPD group exhibited markedly lower FC between the right putamen and the left gyrus rectus as well as the right parahippocampal gyrus; the right superior frontal gyrus and the left gyrus rectus; the anterior cingulate cortex and the olfactory area of the frontal lobe, the left gyrus rectus, and the right superior parietal gyrus; the left temporal pole and the left orbitofrontal cortex as well as the left olfactory area ( P<0.05). Correlation analyses revealed no statistically significant associations between altered FC values and clinical scale scores in the EOPD group. Conclusions:Patients with EOPD demonstrate impaired nigrostriatal dopaminergic function, regional cortical hypometabolism, and aberrant functional connectivity across multiple brain networks.

Objective:To analyze the differentially diagnostic ability of metabolic parameters of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography(18F-FDG PET/CT)in thymic epithelial tumors(TETs)of different histological types.Methods:A total of 72 patients who underwent 18F-FDG PET/CT examination and were confirmed as TETs before treatment at the Department of Nuclear Medicine of the First Medical Center of Chinese PLA General Hospital between January 2013 to May 2022 were analyzed.The patients were divided into thymic tumor with low risk group(9 cases),thymic tumor with high risk group(15 cases)and thymic cancer group(9 cases)according to histological type.The clinical data of patients were recorded,and the patients were staged according to pathological Masaoka-Koga staging of thymic tumor surgery.The maximum standardized uptake value(SUVmax),average standardized uptake value(SUVmean),metabolic tumor volume(MTV),total lesion glycolysis(TLG)and standardized uptake value ratio(SUVR)of the lesions were recorded respectively.The differences of metabolic parameters of various group were compared.The area under curve(AUC)value of receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of 18F-FDG PET/CT in TETs of different histological types.Results:The results of analyzing each metabolic parameter of three groups indicated that the SUVmax,SUVmean and SUVR values of thymic tumor with high risk group and thymic cancer group were significantly higher than them of thymic tumor with low risk group,and the differences were significant(F=10.315,8.336,11.593,P<0.05),respectively.SUVR has the highest diagnostic efficacy in the differential diagnosis for thymic tumor and thymic cancer(AUC:0.864,sensitivity:83.3%,specificity:75.0%),and for thymic tumor with high-risk and thymic cancer(AUC:0.832,sensitivity:56.3%,specificity:100.0%).In addition,SUVR has the highest diagnostic efficacy for thymic tumor with high-risk and thymic tumor with low-risk(AUC:0.748,sensitivity:80.0%,specificity:66.7%).Conclusion:The metabolic parameters of 18F-FDG PET/CT have a certain of differential and diagnostic value in identifying TETs of different histological types.

Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.

OBJECTIVE:There are many kinds of biological scaffolds used for pulp revascularization in clinical practice,and the difference of efficacy between different scaffolds is controversial.The efficacy of nine kinds of biological scaffolds in endodontic revascularization was evaluated by Bayesian network meta-analysis.METHODS:The computer was used to search the literature in CNKI,VIP,WanFang,China Biomedical Literature Service System,PubMed,Cochrane Library,Web of Science,Embase,and Scopus databases.Randomized controlled trials of different biological scaffolds for the treatment of pulp revascularization in young permanent teeth meeting inclusion criteria were collected from each database up to April 1,2024.Two researchers sifted through the literature,data collection,sorting and extraction were completed independently,and the quality of the included literature was assessed for risk of bias.A network meta-analysis was performed using BUGSnet1.1.1 package of R4.2.0 software.RESULTS:A total of 22 studies with 926 affected teeth and 9 different interventions were included in this study.The results of network meta-analysis showed that:(1)Clinical success rate(primary goal):platelet-rich fibrin was superior to blood clot[OR=1.45,95％CI(0.32,2.69)],and the top three ranking results were:concentrated growth factor(82.77％)＞platelet-rich fibrin(75.38％)＞modified platelet-rich fibrin(62.39％).(2)Increased root length(secondary goal):There was no difference among the 7 biological scaffolds at 1-6 months of follow-up(P＞0.05),the top 3 ranking results of rank probability were:concentrated growth factor(86.25％)＞platelet-rich plasma(53.76％)＞platelet-rich fibrin(51.11％).When followed up for＞6 months and＜12 months,concentrated growth factor was superior to blood clot[MD=9.59,95％CI(0.52,18.40)],the top 3 ranking results of rank probability were:concentrated growth factor(92.42％)＞platelet-rich plasma(56.03％)＞platelet-rich fibrin(55.76％).When followed up for more than 12 months,concentrated growth factor was superior to modified platelet-rich fibrin[MD=11.01,95％CI(0.02,22.72)],the top 3 ranking results of rank probability were:concentrated growth factor(86.95％)＞platelet-rich fibrin(68.61％)＞blood clot combined with collagen(52.5％).(3)Increased root wall thickness(secondary goal):at 1-6 months of follow-up,platelet-rich fibrin was superior to blood clot[MD=11.37,95％CI(4.74,17.71)],the top 3 ranking results of rank probability were:platelet-rich fibrin(93.66％)＞concentrated growth factor(63.11％)＞modified platelet-rich fibrin(50.48％).At＞6 months and＜12 months of follow-up,there was no difference among the 6 biological scaffolds(P＞0.05),the top 3 ranking results of rank probability were:modified platelet-rich fibrin(73.63％)＞platelet-rich fibrin(62.36％)＞concentrated growth factor(56.25％).When followed up for more than 12 months,there was no difference among the 9 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(81.9％)＞platelet-rich plasma(62.67％)＞modified platelet-rich fibrin(59.49％).(4)Pulp vitality(third-level goal):there was no difference among the 6 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(84.22％)＞concentrated growth factor(67.71％)＞platelet-rich fibrin(48.79％).CONCLUSION:Existing evidence shows that the clinical success rate of different scaffolds is higher in pulp revascularization,among which platelet-rich fibrin is better than blood clots.In terms of comprehensive comparison of root length and root wall thickness increase,concentrated growth factor performs best in the follow-up period of 1-6 months and＞6 months and＜12 months,while blood clot combined with collagen performs best after follow-up of more than 12 months;concentrated growth factor performs outstandingly in all levels of goals,and may be more conducive to the continued development of the tooth root than other scaffolds,and has great potential in pulp regeneration treatment.Limited by the quality and quantity of literature,the above conclusions still need to be verified by more high-quality studies.

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

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:There are many kinds of biological scaffolds used for pulp revascularization in clinical practice,and the difference of efficacy between different scaffolds is controversial.The efficacy of nine kinds of biological scaffolds in endodontic revascularization was evaluated by Bayesian network meta-analysis.METHODS:The computer was used to search the literature in CNKI,VIP,WanFang,China Biomedical Literature Service System,PubMed,Cochrane Library,Web of Science,Embase,and Scopus databases.Randomized controlled trials of different biological scaffolds for the treatment of pulp revascularization in young permanent teeth meeting inclusion criteria were collected from each database up to April 1,2024.Two researchers sifted through the literature,data collection,sorting and extraction were completed independently,and the quality of the included literature was assessed for risk of bias.A network meta-analysis was performed using BUGSnet1.1.1 package of R4.2.0 software.RESULTS:A total of 22 studies with 926 affected teeth and 9 different interventions were included in this study.The results of network meta-analysis showed that:(1)Clinical success rate(primary goal):platelet-rich fibrin was superior to blood clot[OR=1.45,95％CI(0.32,2.69)],and the top three ranking results were:concentrated growth factor(82.77％)＞platelet-rich fibrin(75.38％)＞modified platelet-rich fibrin(62.39％).(2)Increased root length(secondary goal):There was no difference among the 7 biological scaffolds at 1-6 months of follow-up(P＞0.05),the top 3 ranking results of rank probability were:concentrated growth factor(86.25％)＞platelet-rich plasma(53.76％)＞platelet-rich fibrin(51.11％).When followed up for＞6 months and＜12 months,concentrated growth factor was superior to blood clot[MD=9.59,95％CI(0.52,18.40)],the top 3 ranking results of rank probability were:concentrated growth factor(92.42％)＞platelet-rich plasma(56.03％)＞platelet-rich fibrin(55.76％).When followed up for more than 12 months,concentrated growth factor was superior to modified platelet-rich fibrin[MD=11.01,95％CI(0.02,22.72)],the top 3 ranking results of rank probability were:concentrated growth factor(86.95％)＞platelet-rich fibrin(68.61％)＞blood clot combined with collagen(52.5％).(3)Increased root wall thickness(secondary goal):at 1-6 months of follow-up,platelet-rich fibrin was superior to blood clot[MD=11.37,95％CI(4.74,17.71)],the top 3 ranking results of rank probability were:platelet-rich fibrin(93.66％)＞concentrated growth factor(63.11％)＞modified platelet-rich fibrin(50.48％).At＞6 months and＜12 months of follow-up,there was no difference among the 6 biological scaffolds(P＞0.05),the top 3 ranking results of rank probability were:modified platelet-rich fibrin(73.63％)＞platelet-rich fibrin(62.36％)＞concentrated growth factor(56.25％).When followed up for more than 12 months,there was no difference among the 9 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(81.9％)＞platelet-rich plasma(62.67％)＞modified platelet-rich fibrin(59.49％).(4)Pulp vitality(third-level goal):there was no difference among the 6 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(84.22％)＞concentrated growth factor(67.71％)＞platelet-rich fibrin(48.79％).CONCLUSION:Existing evidence shows that the clinical success rate of different scaffolds is higher in pulp revascularization,among which platelet-rich fibrin is better than blood clots.In terms of comprehensive comparison of root length and root wall thickness increase,concentrated growth factor performs best in the follow-up period of 1-6 months and＞6 months and＜12 months,while blood clot combined with collagen performs best after follow-up of more than 12 months;concentrated growth factor performs outstandingly in all levels of goals,and may be more conducive to the continued development of the tooth root than other scaffolds,and has great potential in pulp regeneration treatment.Limited by the quality and quantity of literature,the above conclusions still need to be verified by more high-quality studies.

Objective To observe the value of improved marching cubes(MC)algorithm based on Monte Carlo sampling and multi-feature analysis for reconstructing head and abdominal CT images.Methods Totally 69 head axial CT images from one patient with glioma and 108 abdominal axial CT images from another patient with liver cancer were retrospectively enrolled,while 98 head axial CT images of males in visible human project dataset were included.Monte Carlo sampling and multi-feature analysis were introduced into MC algorithm.Monte Carlo sampling was used to simulate the uncertainty of voxel values and estimate the probability of voxels belonging to the isosurface,and dynamic thresholds were generated through combining gradient,curvature,local variance and distance term features of voxels.Then head and abdominal CT images were reconstructed with improved MC algorithm,which were compared with those reconstructed with traditional MC and probabilistic MC(PMC)algorithms.Results Compared with traditional MC and PMC algorithms,improved MC algorithm had lower mean square error,higher signal-to-noise ratio,peak signal-to-noise ratio and computation time for reconstructing head and abdominal CT images without significant difference of Dice similarity coefficient nor recall rate,which could keep the structural loss rate and morphological change rate at low level.Conclusion Improved MC algorithm based on Monte Carlo sampling and multi-feature analysis could significantly improve the robustness and edge accuracy for reconstructing head and abdominal CT images,but the computational efficiency and preservation of head structural details still needed to be optimized.