China is currently in an accelerated stage of population aging, and brain diseases pose a significant threat to the health of the elderly. " Preventing brain aging and maintaining brain health" has become a high-level goal of healthy aging. During the process of aging, the physiological and psychological states of elderly people change, making them prone to nervousness and exhaustion, which can disturb the brain spirit, damage the brain collaterals, and severely endanger brain health. Starting from the holistic view of cultivating both body and spirit in traditional Chinese medicine, based on the physical and mental characteristics of the elderly, this paper applies the concept and method of " relaxation and tranquility" in the protection of elderly brain health, focusing on maintaining relaxation and tranquility in both physical and mental aspects. Specific measures include emphasizing subjective consciousness, relaxing the heart and calming down; utilizing the daoyin method, relaxing the body and calming down, combining relaxation and tranquility, cultivating both body and spirit to prevent diseases and protect the brain, which enables the elderly to have a healthy mind and body, a sense of happiness and fulfillment, and to age gracefully. Simultaneously, advocating for tranquility is also called " respect" for relaxation, following nature to understand constant changes, and improving one′s ability to think positively in old age, in order to expand ideas for the protection of elderly brain health.

Myocardial fibrosis （MF）， characterized by decreased cardiac function and myocardial compliance， is a pathological process and a progression factor in various cardiovascular diseases. The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome is closely related to the development of MF. Recent studies have shown that traditional Chinese medicine （TCM） can regulate the NLRP3 inflammasome to alleviate MF. Based on this， this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF. It is found that active ingredients of TCM， such as alkaloids （lycorine，vincristine，bufalin）， saponins （astragaloside Ⅳ， diosgenin，ginsenoside Rg3）， terpenoids （celastrol，oridonin）， and phenols （polydatin，curcumin，phloridzin） as well as TCM formulas （Zhachong shisanwei pills，Zhilong huoxue tongyu capsules， Luqi formula） can inhibit the activation of the NLRP3 inflammasome， thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18， reducing inflammatory damage to myocardial tissue， alleviating excessive deposition of the extracellular matrix， and thus exerting the effect of improving MF.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective : To explore the correlation between uteroglobulin-related protein 1(UGRP1) and primary hypothyroidism. Methods : Ninety-six patients with primary hypothyroidism were selected, including 66 patients with positive thyroid peroxidase antibodies(TPOAb) or anti-thyroglobulin antibodies(ATG) as the antibody-positive group, 30 patients with negative thyroid autoantibodies as the antibody-negative group, and 96 healthy people as the control group. The general clinical data, thyroid-related indicators and serum UGRP1 levels were compared among these three groups. Human thyroid normal cells(NTHY-ORI 3-1) were transfected with plasmids in vitro, thus establishing the control group as well as the UGRP1 group. Enzyme linked immunosorbent assay(ELISA) was used to detect and compare the T4 level in the cell culture supernatant. Results : The differences in thyroid stimulating hormone(TSH), TPOAb and ATG among the three groups were statistically significant(P<0.05). The serum UGRP1 levels in the antibody-positive(303.97±156.00) pg/ml and antibody-negative groups(352.13±188. 37) pg/ml were higher than those in the control group( 237. 54 ± 137. 20) pg/ml,and the differences between the groups were statistically significant( P = 0. 005). Meanwhile,there was no statistically significant difference between the antibody-positive and antibody-negative groups. Multi-factor Logistic regression analysis showed that UGRP1 was the risk factor for the occurrence of primary hypothyroidism( OR = 1. 004,95% CI: 1. 001-1. 007,P =0. 007). The difference between the control group and UGRP1 group in T4 concentration secreted by human thyroid normal cells was not statistically significant. Conclusion Serum UGRP1 levels increase in patients with primary hypothyroidism,and the high expression of UGRP1 may have no direct relation to the function of thyroid cells secreting T4.

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

Objective: To analyze the prevalence and related factors of pediatric flexible flatfoot (PFF) among 7-8 year old children in Changzhou, so as to provide a feasible basis for the prevention and treatment of PFF. Methods: From December 2023 to February 2024, a total of 1 685 children aged 7-8 from 10 primary schools in Changzhou were selected by stratified cluster random sampling method, and screened for PFF by using a foot optical assessment recording device. Information including sex, body mass index (BMI), diet, exercise and shoe wearing habits were collected. The valgus angle of the hindfoot was measured on the body surface by using an orthopedic measuring ruler in the standing position. Pain levels were evaluated by using visual analogue score (VAS) for children with flatfoot syndrome. Multivariate Logistic analysis was used to analyze related factors of PFF. Results: The overall detection rate of PFF was 27.4%, and there was a significant difference in the detection rate of PFF between boys and girls, with 30.3% and 24.1% respectively ( χ 2=7.96, P < 0.01 ). Most cases of PFF were mild flatfoot (60.8%) and bilateral ( 60.4% ). Approximately 13.2% of children with PFF had flatfoot syndrome, with a mean VAS of (2.86±0.73). About 56.1% of children with PFF had a normal valgus angle of the hindfoot. Sex, high BMI and preference for shoe last with front upturned shoe shape were positively correlated with the detection of PFF ( OR= 1.74, 1.54, 1.13, P <0.05). After stratified by sex, regular exercise in boys and age in girls were negatively correlated with the detection of PFF ( OR=0.40, 0.64, P <0.05). Conclusions The detection rate of PFF in 7-8 year old children is high. Additionally, PFF combined with flatfoot syndrome or valgus hindfoot is relatively rare and is likely to be underestimated, which emphasizes the importance of early detection and intervention for PFF.

Objective:This study evaluates the agreement between a new low-load sleep monitoring system, QSA600, based on millimeter-wave radar technology, and polysomnography (PSG) in diagnosing obstructive sleep apnea (OSA).Methods:A total of 155 subjects were recruited for a parallel agreement study in the sleep laboratory of the Department of Otorhinolaryngology Head and Neck Surgery at Shanghai Sixth People′s Hospital from July to September 2023. The subjects underwent simultaneous monitoring with both PSG and the QSA600 system. One hundred and forty-five subjects consisting of 75 males and 70 females included in the final analysis, with an average age of (35.30±12.41) years, an average height of (168.23±8.08) cm, and an average weight of (68.28±13.74) kg. The subjects were divided into four groups based on the apnea-hypopnea index (AHI): <5.0 events/h (non-OSA group, 39 cases), ≥5.0-<15.0 events/h (mild OSA group, 47 cases), ≥15.0-<30.0 events/h (moderate OSA group, 25 cases), and≥30.0 events/h (severe OSA group, 34 cases). Intraclass correlation coefficients (ICC), Pearson correlation coefficients ( r), and Bland-Altman analysis were employed to assess the agreement between the two monitoring techniques regarding AHI and other parameters. Sensitivity and specificity of the QSA600 in diagnosing OSA were evaluated at different AHI thresholds. Statistical analyses were conducted using MATLAB R2022a. Results:Using AHI 5 events/h, 15 events/h and 30 events/h as thresholds, the sensitivity for diagnosing mild, moderate, and severe OSA was 88.68%, 89.83% and 97.06%, respectively. The specificity was 94.87%, 98.84% and 99.10%, respectively. The areas under the receiver operating characteristic (ROC) curve was 0.973 4, 0.990 9 and 0.999 5, respectively. The comparison of key indicators between QSA600 and PSG diagnostic results revealed:a Pearson correlation coefficient of 0.987 2( P<0.001) between the AHI measurement values. The mean difference between the Bland-Altman measurement values of the two was -1.43(95% CI:-8.74-5.88) events/h and the ICC between the two was 0.985 0(95% CI: 0.975 4-0.990 4). Conclusions:As a new low-load sleep monitoring system, QSA600 demonstrates high concordance with traditional PSG in diagnosing OSA and stratifying its severity, which has promising potential for clinical application. (Clinical trial registration number: NCT06038006)

Purpose To explore the application value of combining 18F-FDG PET images with interpretable deep learning radiomics(IDLR)models in the differential diagnosis of primary Parkinson's disease(IPD)and atypical Parkinson's syndrome.Materials and Methods This cross-sectional study was conducted using the Parkinson's Disease PET Imaging Benchmark Database from Huashan Hospital,Fudan University from March 2015 to February 2023.A total of 330 Parkinson's disease patients underwent 18F-FDG PET imaging,both 18F-FDG PET imaging and clinical scale information were collected for all subjects.The study included two cohorts,a training group(n=270)and a testing group(n=60),with a total of 211 cases in the IPD group,59 cases in the progressive supranuclear palsy(PSP)group,and a group of 60 patients with multiple system atrophy(MSA).The clinical information between different groups were compared.An IDLR model was developed to extract feature indicators.Under the supervision of radiomics features,IDLR features were selected from the features collected by neural network extractors,and a binary support vector machine model was constructed for the selected features in images of in testing group.The constructed IDLR model,traditional radiomics model and standard uptake ratio model were separately used to calculate the performance metrics and area under curve values of deep learning models for pairwise classification between IPD/PSP/MSA groups.The study conducted independent classification and testing in two cohorts using 100 10-fold cross-validation tests.Brain-related regions of interest were displayed through feature mapping,using gradient weighted class activation maps to highlight and visualize the most relevant information in the brain.The output heatmaps of different disease groups were examined and compared with clinical diagnostic locations.Results The IDLR model showed promising results for differentiating between Parkinson's syndrome patients.It achieved the best classification performance and had the highest area under the curve values compared to other comparative models such as the standard uptake ratio model(Z=1.22-3.23,all P<0.05),and radiomics model(Z=1.31-2.96,all P<0.05).The area under the curve values for the IDLR model in differentiating MSA and IPD were 0.935 7,for MSA and PSP were 0.975 4,for IPD and PSP were 0.982 5 in the test set.The IDLR model also showed consistency between its filtered feature maps and the visualization of gradient-weighted class activation mapping slice thermal maps in the radiomics regions of interest.Conclusion The IDLR model has the potential for differential diagnosis between IPD and atypical Parkinson's syndrome in 18F-FDG PET images.

Objective:To investigate the role and mechanism of long non-coding RNA (lncRNA) gastric cancer associated transcript 3 (GACAT3) in glioma radioresistance.Methods:Real-time reverse transcription PCR (RT-qPCR) was used to detect the expression of lncRNA GACAT3 and miR-497 in human astrocyte NHA cells and glioma cells U251. NC-siRNA and GACAT3-siRNA were transfected into U251 cells, and the cells were treated with X-ray irradiation. Colony formation assay was used to detect the survival fraction of U251 cells. The apoptosis of U251 cells was detected by flow cytometry. Western blot was used to detect the expression of cysteine containing aspartate specific protease 3 (Caspase-3) in U251 cells. Bioinformatics software and dual luciferase reporter gene assay were used to predict and verify the targeting relationship between lncRNA GACAT3 and miR-497, and between miR-497 and Yes-associated protein 1 (YAP1), respectively. NC mimic, miR-497 mimic, GACAT3-siRNA and NC inhibitor, GACAT3-siRNA and miR-497 inhibitor were co-transfected into U251 cells. Colony formation assay, flow cytometry and Western blot were adopted to evaluate the effect of miR-497 overexpression and lncRNA GACAT3 on the radiosensitivity of U251 cells by regulating miR-497.Results:Compared with NHA cells, the expression of lncRNA GACAT3 in U251 cells was significantly up-regulated, and the expression of miR-497 in U251 cells was significantly down-regulated (both P<0.05). After knockdown of GACAT3, the survival fraction of irradiated U251 cells was significantly decreased, while the apoptosis rate and Caspase-3 protein expression were significantly increased (all P<0.05). lncRNA GACAT3 targeted and negatively regulated the expression of miR-497. Overexpression of miR-497 significantly reduced the survival fraction of U251 cells after irradiation, and increased the apoptosis rate and Caspase-3 protein expression. Inhibition of miR-497 significantly reversed the promoting effect of lncRNA GACAT3 knockdown on the radiosensitivity of U251 cells. miR-497 targeted and negatively regulated the expression of YAP1. Conclusion:Knockdown of lncRNA GACAT3 can enhance the radiosensitivity of glioma cells by regulating the miR-497/YAP1 axis.

Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.