OBJECTIVE To investigate the effects of Brassica rapa polysaccharide （BRP） on the Toll-like receptor 4 （TLR4）/ myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1c （SREBP-1c） pathways， intestinal microbiota and liver metabolism of mice with alcoholic liver injury， and preliminarily elucidate its mechanism for improving alcoholic liver injury. METHODS Seventy-two mice were randomly divided into blank group （normal saline）， model group （normal saline）， bifendate group （positive control， 300 mg/kg） and BRP low-， medium- and high-dose groups （75， 150 and 300 mg/kg）. They were given relevant medicine intragastrically， once a day， for consecutive 9 d. After the last administration， mice in all groups except the blank group were gavaged with white liquor to establish an alcoholic liver injury model. The levels of alanine aminotransferase and aspartate aminotransferase in serum， total cholesterol， triglycerides， low-density lipoprotein cholesterol， interleukin-6， interleukin-1β， tumor necrosis factor- α and lipopolysaccharide， as well as protein expressions of TLR4， MyD88， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， AMPK， phosphorylated AMPK （p-AMPK）， and SREBP-1c were all detected； pathological morphological changes of liver tissue and colon were observed. 16S rRNA was used to detect the changes of intestinal microbiota in mice， and metabolomics 2022B02058） technology was used to detect the changes of liver metabolites. RESULTS Compared with model group， the above biochemical indicators and the protein expressions of TLR4， MyD88， p-NF-κB p65， and SREBP-1c in liver tissues were all significantly decreased （P＜0.05 or P＜0.01）， while the protein expression of p-AMPK was significantly increased （P＜0.05 or P＜0.01）. Pathological damage to liver and colon tissues was significantly improved. Medium dose of BRP could increase the relative abundance of Akkermansia， norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group in the intestinal contents of mice to a certain extent， and decrease the relative abundance of Lactobacillus and Escherichia-Shigella. A total of 9 differential metabolites were identified by metabolomics， including homogentisic acid， myristyl lysophosphatidylcholine， which were involved in pathways such as tyrosine metabolism. CONCLUSIONS BRP can regulate the relative abundance of beneficial flora， reduce the relative abundance of harmful flora， improve the structure of intestinal colonies， reduce the entry of pro-inflammatory mediator lipopolysaccharides into liver tissue， affect metabolic pathways such as tyrosine metabolism and the expression of TLR4/MyD88/NF- κB and AMPK/SREBP-1c signaling pathways in the liver， and ultimately improve alcoholic liver injury.

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Objective To investigate the effect of fear-induced stress during pregnancy on the expression of glucose transporters(GLUT)in the placenta,providing evidence for the theory of fetal damage caused by fear-induced stress during pregnancy.Methods Twenty pregnant Wistar rats were randomly divided into a control group and a model group of 10 rats each.In the model group,a fear-induced stress model was established using the modified bystander electroshock method for 20 days.After the experiment,the number of offspring and the weights of the placenta and fetal rats were measured,and the placental efficiency was calculated.Transmission electron microscopy was used to observe the morphological changes of placental cells.Bioinformatics analysis was performed to screen for differential genes in placentas affected by pregnancy stress-phobia,and gene set enrichment analysis was performed.Protein immunoblotting(Western Blot),Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR),and immunohistochemistry were used to detect the expression levels of GLUT1,GLUT3,GLUT6,and GLUT7 proteins and genes.Results The placental efficiency was significantly reduced in the model group compared with that in the control group.The result of transmission electron microscopy in the model group showed that the placental microvilli were sparse and short and that the mitochondria and endoplasmic reticulum were swollen.Gene set enrichment analysis revealed that placental genes were significantly enriched in cellular glucose homeostasis in the model group compared with those in the control group.The result of Western Blot,Real-time PCR,and immunohistochemistry indicated a decrease in both the protein and gene expression levels of GLUT1,GLUT6,and GLUT7 in the placenta of pregnant rats.Conclusions Prenatal exposure to fear-induced stress may lead to adverse pregnancy outcomes.These adverse outcomes are potentially associated with reduced levels of three key GLUTs in the placenta:GLUT1,GLUT6,and GLUT7.

Objective To investigate the effects and mechanisms of five-element music on the social behavior of the children of mothers with fear stress during pregnancy and provide a basis for the early prevention and treatment of clinical fetogenic affective disorders.Methods Forty-five pregnant mice were randomly divided into three groups:a control group,model group,and five-element music group.The model and five-element music group models were established using the bystander electric shock method.Additionally,the five-element music group was exposed to Palace Tune five-element music daily from 17:00 to 19:00 during pregnancy.On the 19th day of pregnancy,ELISA was employed to assess the levels of adrenocorticotropin(ACTH)and cortisol(CORT)in the serum of pregnant mice in each group for modeling evaluation.The offspring were subsequently grouped with their mother and underwent an 8-week-old three-box social experiment to observe their social behavior.We used the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the medial prefrontal cortex(mPFC)of the offspring.High-performance liquid chromatography was employed to measure the total glutamate(Glu)content in the mPFC,while Gorky staining was used to observe changes in the dendritic spines of mPFC neurons in the offspring.Results Compared to those in the blank group,pregnant mice in the model group exhibited a significant increase in the levels of ACTH and CORT in their serum,and there was a significant decrease in the social interaction time and social novelty preference index of their offspring.There was also a significant decrease in glutamate neuron activity,glutamate content,and neuronal dendritic spine density.In contrast,compared with those in the model group,pregnant mice in the five-element music group demonstrated a reduction in the levels of ACTH and CORT in the serum,and there were improvements in the social behavior,glutamate neuron activity,glutamate content,and condition of neuronal dendritic spines in the offspring.Conclusions Intervention with five-element music effectively ameliorated the offspring's social behavior disorder result ing from prenatal fear stress;the mechanism was potentially linked to enhanced glutamate neuron activity in the mPFC region.

Objective:To explore the value of the classifier model based on CT radiomic characteristics in predicting the activity of pulmonary cystic echinococcosis (CE).Methods:The study was designed as cross-sectional. A retrospective analysis was performed on 81 patients diagnosed with pulmonary CE in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to October 2020. The Python function divided 17 cases into an internal verification group and 64 cases into a training group with a ratio of 2∶8. In addition, 16 patients diagnosed with pulmonary CE from the Fourth Affiliated Hospital of Xinjiang Medical University from October 2020 to 2024 were included in the external validation group. All patients underwent CT examination, and radiomics features were extracted using Radcloud platform of Huimedi Huiying. The intraclass correlation coefficient was performed on the features, then feature screening was performed using the SelectKBest method, variance thresholding method, and least absolute shrinkage and selection operator. Finally, three classifiers (including support vector machine (SVM), K-neighborhood (KNN), and logistic regression (LR)) were used to build the models. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the model′s efficiency.Results:Among 81 patients with lung CE, 58 were male, and 23 were female. twenty-eight lesions were active and 53 were inactive. A total of 11 optimal features were selected. Based on the selected features, the SVM classifier model, KNN classifier model, and LR classifier model were established. The KNN classifier model in the training group had the highest AUC value (0.93) and the highest specificity (0.98) in predicting lung CE activity. In the internal validation group, the SVM classifier model had the highest AUC value (0.92) and the highest specificity (0.91) in predicting lung CE activity. The LR classifier model performed best with the highest AUC of 0.85 for predicting lung CE activity in the external validation group, and the specificity of the three models was 0.92.Conclusion:The classifier model established based on CT radiomic features has a certain value in predicting lung CE activity, and may be helpful in clinical decision-making.

Background and Purpose:The early prediction of local tumor progression-free survival(LTPFS)after radiofrequency ablation(RFA)for colorectal cancer(CRC)lung metastases has significant clinical importance.The application of radiomics in the prediction of tumor prognosis has been explored.This study aimed to construct a radiomics-based nomogram for predicting LTPFS after RFA in CRC patients with lung metastases.Methods:This study retrospectively analyzed 172 CRC patients with 401 lung metastases admitted to Department of Interventional Radiology,Fudan University Shanghai Cancer Center from August 2016 to January 2019.This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:2402291-24).After augmentation of pre-ablation and immediate post-ablation computed tomography(CT)images,the target metastases and ablation regions were segmented manually to extract the radiomic features.Maximum relevance and minimum redundancy algorithm(MRMRA)and least absolute shrinkage and selection operator(LASSO)regression models were applied for feature selection.The clinical model,the radiomics model,and the fusion model were constructed based on the selected radiomic features and clinical variables screened by the multivariate analysis.The Harrell concordance index(C-index)and area under receiver operating characteristic(ROC)curves(AUC)were calculated to evaluate the prediction performance.Finally,the corresponding nomogram of the best model was drawn.Results:Among all the lung metastases,102(25.4%)had final recurrence,and 299(74.6%)had complete response(CR).The median follow-up time was 21 months(95%CI:19.466-22.534),and the LTPFS rates at 1,2,and 3 years after RFA were 76.5%(95%CI:72.0-80.4),72.1%(95%CI:66.6-76.9)and 69.9%(95%CI:64.0-75.1).In both the training and test dataset,the fusion model based on the final 12 radiomic features through the LASSO regression and 4 clinical variables screened by multivariate analysis achieved the highest AUC values for LTPFS,with C-index values of 0.890(95%CI:0.854-0.927)and 0.843(95%CI:0.768-0.916),respectively.Conclusion:The fusion model based on radiomic features and clinical variables is feasible for predicting LTPFS after RFA of CRC patients with lung metastases,whose performance is superior to the single radiomic and clinical model.At the same time,the nomogram of the fusion model can intuitively predict the prognosis of CRC patients with lung metastases after RFA,thus assisting clinicians in developing individualized follow-up review plans for patients and adjusting treatment strategies flexibly.

This article summarizes the clinical experience in treatment of refractory tinnitus with He's santong therapy of acupuncture (three techniques of acupuncture to remove the blockage and promote circulation). Refractory tinnitus is characterized by a mixture of deficiency and excess, which is implicated in the dysfunction of zangfu organs, resulting in physical and mental injuries. In association with the complicated conditions of the diseases and etiology, He's santong therapy of acupuncture is adopted. The needling with filiform needles acts directly on the affected site to regulate the mind and improve the hearing, the fire needling works on removing the refractory illness and blockage through heating up, and bloodletting on activating blood circulation and promoting qi flowing to eliminate the pathogens. The three techniques of acupuncture co-work on harmonizing the mind, promoting the circulations in the ear to stop tinnitus.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Middle Aged ; Adult ; Female ; Acupuncture Points

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

【Objective】 To investigate the current status of incision sites to obtain intact specimens in laparoscopic nephrectomy by urologists in China, so as to provide reference for the standardized procedure. 【Methods】 During Jun.20, 2021 and Jul.4, 2021, more than 20 000 urologists in a WeChat group were surveyed with a questionnaire. The general data, incision sites and related complications were statistically analyzed. 【Results】 A total of 601 valid questionnaires were collected, covering urologists from 31 provinces, autonomous regions and municipalities. Surgical approaches: 68 urologists chose trans-abdominal approach, 432 chose posterior abdominal space approach, 101 chose both surgical approaches. Incision sites: 97 urologists chose lumbar transverse incision, 202 chose dorsal oblique incision of the waist, 119 chose ventral oblique incision, 93 chose the paramedian incision, 112 chose the lower abdominal oblique incision (Gibson), 11 chose the transverse lower abdominal incision (Pfannenstiel), 7 chose the median incision of the lower abdomen, 2 chose the median incision in the upper abdomen, 15 chose axillary midline direct incision; 399 chose to cut off the muscles, and 202 chose not to. Complications: 232 urologists reported pain after 2 weeks, 369 reported no pain; 325 reported numbness after 2 weeks, 276 reported no numbness; 66 reported incisional hernia, 535 reported no hernia. 【Conclusions】 Chinese urologists tend to choose retroperitoneoscopic nephrectomy and waist incision to obtain intact specimens. Transperitoneal laparoscopic nephrectomy has a variety of incisions for intact specimens. There is no standardized incision sites to obtain intact specimens.