Objective To investigate the differences in emotional processing characteristics and electroencephalography （EEG） power values in patients with Parkinson disease （PD）. Methods A total of 24 PD patients were enrolled as subjects， and 30 healthy individuals were enrolled as control group. With the use of the EPIE experimental paradigm， SAM questionnaire was used to determine the scores of emotional valence and arousal， and EEG was used for real-time monitoring of cortical EEG signals. The two groups were compared in terms of the differences in valence/arousal and EEG power values under different emotions and their correlation. Results The PD group had significantly higher BAI and BDI scores than the control group[BAI（16.92±3.83）vs（11.62±3.65），t=4.521，P<0.05；BDI（22.69±2.30）vs（14.17±4.06），t=7.981，P<0.05]. In the negative mood， there were significant differences in valence/arousal between the two groups （t=4.505，-7.705，bothP<0.05）. There were significant differences between the two groups in power values at Fp1，Fp2，F7，F3，F4，T3，T4， and T5（t=-4.12，-12.43，5.76，-2.90，-4.72，-5.34，-5.81，-2.65，all P<0.05）. In the negative mood， for the control group， valence score was correlated with Fp1 （r=-0.837， P<0.01）， Fp2 （r=-0.920， P<0.01），F4（r=-0.604，P=0.008），P3（r=-0.658，P=0.003），and P4（r=-0.546，P=0.019）， and arousal score was correlated with Fp1（r=0.887， P<0.01）， Fp2 （r=0.958， P=0.003），F4（r=0.683，P=0.003），P3 （r=0.721， P=0.003），and P4 （r=0.610，P=0.007）； for the PD group， valence score was correlated with Fp2（r=-0.490，P=0.015） and F7（r=-0.564，P=0.004）， and arousal score was correlated with Fp2 （r=0.440， P=0.031） and F7（r=0.853，P<0.01）. Conclusion Patients with PD have negative emotional processing abnormalities associated with right PFC and left lateral FL.
Electroencephalography

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

On the basis of that the fluorescence wavelength of copper nanoclusters(CuNCs)could cover the entire visible region,multicolor fluorescent CuNCs/starch composites were prepared and applied in fingermark development.With L-glutathione as the reducing agent and protective ligand,blue emissive and orange emissive CuNCs solutions were obtained in alkaline solutions at 90℃and 25℃,respectively.With the aggregation-induced emission effect induced by ethanol as a poor solvent,the fluorescence of orange emissive CuNCs with a higher intensity was achieved in an ethanol-water solution.With ascorbic acid as the reducing agent and 3-mercaptopropionic acid as the protective agent,green emissive CuNCs solution was prepared in an acid solution.Particle morphologies,chemical compositions and optical properties of these three CuNCs above were investigated using physical characterization and spectroscopic analysis,indicating that well-dispersed CuNCs had excellent photoluminescent properties.These CuNCs solutions were combined with starch to form composite powders by simply drying.The influences of the type of CuNCs and the ratio of CuNCs to starch on the emission wavelength and fluorescence intensity of the products were studied.The obtained CuNCs/starch composites could emit blue,green and orange fluorescence under 365 nm ultraviolet light,respectively,which were suitable for fingermark development.Minutiae and partial level-3 features of latent fingermarks could be effectively developed.High-quality fluorescence fingermark images would be captured using appropriate optical filters to eliminate background interference of various substrates.

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.