Objective: To explore the bidirectional causal relationship between 731 immune cell phenotypes and recurrent aphthous ulcers (RAU) using Mendelian randomization (MR). Methods: A two-sample bidirectional MR study was conducted using publicly available genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and the RAU GWAS summary data from the FinnGen consortium. The inverse-variance weighted (IVW) method was used as the primary analysis tool, with supplementary analyses including the weighted median (WM) method, MR-Egger regression, weighted mode, and simple mode. Sensitivity analyses were conducted using Cochran’s Q test, the mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method for detecting pleiotropy and outliers, and leave-one-out cross-validation. Furthermore, differential analysis was performed using a clinical cohort dataset from the Gene Expression Omnibus (GEO) to further validate the MR results. Results: In the forward MR analysis, 731 immune cell phenotypes were considered as exposures and RAU as the outcome. Among them, 52 immune cell phenotypes showed a significant causal effect on RAU (P<0.05). After false discovery rate (FDR) correction, two immune phenotypes remained significantly associated with RAU risk: with increased monocyte-derived myeloid suppressor cells (M-MDSC) (OR = 1.06; 95% CI: 1.03-1.09) and CD33 on granulocytic myeloid-derived suppressor cells (G-MDSC) (OR = 1.06; 95% CI: 1.03-1.09), the risk of RAU also increased. In reverse MR, RAU was found to have a significant causal effect on two immune cell phenotypes (P<0.05), but no significant effects were found after FDR correction. Sensitivity analysis showed no significant heterogeneity between SNPs (P>0.05). Differential analysis of the GEO dataset revealed that the characteristic genes of myeloid-derived suppressor cells (MDSC) (CTBS, IPMK, and UBA3) were significantly upregulated in RAU (P<0.05). Conclusion The MR results of 731 immune cell phenotypes suggest that M-MDSC and CD33 molecules on G-MDSC may be risk factors for RAU development. The clinical GEO dataset further validated that MDSC may play a role in RAU, while RAU did not show a significant causal association with the 731 immune cell phenotypes.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Objective To investigate the effect of miR-495-3p targeting budding uninhibited by benzimidazoles(BUB1)on signal transducer and activator of transcription 3(STAT3)signaling pathway on biological behavior of esophageal cancer(EC)cells.Methods The differentially expressed genes in EC tissues and normal tissues were screened by the cDNA microarray technique.The differentially expressed genes were analyzed by bioinformatics methods.The target genes of miRNAs were predicted by the TargetScan database and verified by a dual luciferase gene reporter assay.KYSE150 cells were divided into blank control group,NC mimics group and miR-495-3p mim-ics group.The activity of KYSE150 cells were detected by the CCK-8 method.Cell cycle and apoptosis were meas-ured by flow cytometry.The expression of BUB1 mRNA was measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR).The levels of BUB1,STAT3,phosphor(p)-STAT3,cyclin dependent kinase 1(CCNB1),cyclin dependent kinase 1(CDK1),B-cell lymphoma-2(Bcl-2),cysteinyl aspar-tate-specific proteinase-3(Caspase-3)and cysteinyl aspartate-specific proteinase-3(Caspase-9)were measured by Western blot.The migration and invasion abilities of the cells were measured by wound-healing and Transwell inva-sion assays.Results Differentially expressed genes were involved in biological processes,signaling pathways and network construction,which were mainly related to cell cycle.BUB1 is the key(Hub)gene,and BUB1 is the tar-get gene of miR-495-3p.In vitro experiments showed that overexpression of miR-495-3p could significantly inhibit the migration and invasion of EC cells and induce apoptosis and G2/M phase arrest.After treatment with overex-pression of miR-495-3p,the expression of Caspase-3 and Caspase-9 in EC cells increased significantly(P＜0.01),while the expression of Bcl-2,BUB 1,CCNB1,CDK1 and p-STAT3 decreased significantly(P＜0.01).Moreover,the STAT3 signaling pathway might play an important role in this process.Conclusion miR-495-3p may influence the biological behavior of esophageal cancer cells by down-regulating BUB 1-mediated STAT3 signaling pathway.

ObjectiveTo investigate the mechanism of Baitouweng Tang in inhibiting the growth of esophageal cancer （EC） cells by regulating budding uninhibited by benzimidazoles 1 （BUB1）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodGene chip technology was used to explore the differential gene expression between esophageal cancer tissues and normal tissues and identified differentially expressed genes. The differentially expressed genes were analyzed by bioinformatics methods. EC cells were treated with 25， 50， 100， 200， 400， 800 mg·L^-1 Baitouweng Tang. EC cell viability was detected by Thiazolyl Blue （MTT） colorimetry. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 was measured by real time quantitative polymerase chain reaction （Real-time PCR）. The protein levels of BUB1， STAT3， phosphorylated （p）-STAT3， Cyclin B1 （CCNB1）， cyclin-dependent kinase 1 （CDK1）， B-cell lymphoma-2 （Bcl-2）， cysteinyl aspartate-specific proteinase（Caspase）-3， and Caspase-9 were measured by Western blot. The migration and invasion abilities of the cells were measured by wound-healing and Transwell invasion assays. ResultDifferentially expressed genes were primarily involved in biological processes， signaling pathways， and network construction related to cell mitosis， with BUB1 identified as a key core gene. Compared with the control group， Baitouweng Tang inhibited BUB1 expression （P<0.05，P<0.01）. In vitro experiments showed that compared with the control group， Baitouweng Tang could significantly inhibit the growth （P<0.05，P<0.01）， migration and invasion （P<0.05，P<0.01） of EC cells， induce apoptosis （P<0.05，P<0.01）， and cause G₂/M phase increase （P<0.01）. After treatment with Baitouweng Tang， compared with the results in the control group， the expression of Caspase-3， and Caspase-9 in EC cells increased significantly （P<0.05，P<0.01）， while the expression of Bcl-2， BUB1， CCNB1， and CDK1 decreased significantly （P<0.05，P<0.01）. Moreover， the STAT3 signaling pathway was also found to play an important role in this process. ConclusionBaitouweng Tang may inhibit the growth of EC cells by downregulating BUB1 and mediating the STAT3 signaling pathway.

Objective To observe the effects of different frequencies of electroacupuncture on the degree of atrophy of quadriceps femoris in rabbits with anterior cruciate ligament(ACL)injury model;To explore the possible mechanisms of electroacupuncture in treating ACL injury.Methods Totally 24 New Zealand rabbits were randomly divided into blank group,model group,low-frequency electroacupuncture group and high-frequency electroacupuncture group,with 6 rabbits in each group.Except for the blank group,ACL injury models were established in the other groups.On the 7th day after modeling,the low-frequency electroacupuncture group and the high-frequency electroacupuncture group performed electroacupuncture treatment(continuous wave,frequency of 2 Hz and 100 Hz respectively,and left the needle in place for 20 min)at"Xuehai"and"Liangqiu"of the operation side,and the remaining groups were only grasped and immobilized,for 21 days.The mass ratio of the quadriceps femoris was calculated,the histopathological morphology of the quadriceps femoris tissue of the rabbits in each group was observed by HE staining,the expressions of NO,iNOS in quadriceps femoris tissue were detected by ELISA,the content of ROS in quadriceps femoris tissue was detected by fluorescent probe,the protein expressions of PERK,ATF6,IRE1,MuRF1,MAFbx in quadriceps femoris tissue were detected by Western blot.Results Compared with the blank group,the quadriceps femoris muscle mass ratio of the model group rabbits was significantly reduced(P<0.01),with irregular arrangement of muscle cells,accompanied by swelling and atrophy,significant interstitial edema,and extensive inflammatory infiltration,the contents of NO,iNOS and ROS in quadriceps femoris tissue significantly increased(P<0.01),while the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly increased(P<0.01).Compared with the model group,the quadriceps femoris muscle mass ratio in the low-frequency and high-frequency electroacupuncture groups significantly increased(P<0.01),with regular arrangement of muscle cells,improved swelling and atrophy of cells,and reduced interstitial edema and inflammation,the contents of NO,iNOS and ROS in quadriceps femoris tissue were significantly reduced(P<0.01),and the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly decreased(P<0.01).Moreover,the low-frequency electroacupuncture group had better effects than the high-frequency electroacupuncture group(P<0.05).Conclusion Different frequencies of electroacupuncture intervention in ACL injury rabbits can better delay the degree of quadriceps femoris atrophy,and its mechanism may be related to reducing the expressions of oxidative metabolites NO,iNOS,ROS,and reducing the expressions of endoplasmic reticulum stress-related proteins PERK,ATF6,IRE1 in quadriceps fermoris,which in turn inhibit the expressions of quadriceps atrophy factors MuRF1,MAFbx,and delaying the degradation of quadriceps muscle proteins.The effect of low-frequency electroacupuncture is superior to the high-frequency electroacupuncture.

Objective To analyze and summarize the acupoint selection law of acupuncture and moxibustion for the treatment of temporomandibular joint dysfunction syndrome(TMD)using data mining technology.Methods Clinical literature about acupuncture and moxibustion for the treatment of TMD was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from the establishment of the databases to March 1,2024.Excel 2021 was used to establish a prescription database of acupoints.SPSS Modeler 18.0 and SPSS Statistics 27.0 were used to analyze the frequency of use of acupoints,meridians,locations,specific acupoints,and the analysis of association rules,factor analysis,and clustering analysis.Results A total of 480 articles and 480 prescriptions were included in the study,containing 90 acupoints,with a total frequency of 2 290 times.The high-frequency acupoints were Xiaguan,Hegu,Jiache,Tinggong and Ashi point;the commonly used meridians were the stomach meridian,large intestine meridian,small intestine meridian,bile meridian,and triple-energizer meridian;the most frequently chosen acupoints were the Jiaohui acupoints,Yuan acupoints and Wushu acupoints;and mostly involved acupoints were located at the head and neck area,the upper limb area and the lower limb area.The association analysis showed that the top five combinations were"Xiaguan-Hegu","Xiaguan-Jiache","Xiaguan-Hegu-Jiache","Xiaguan-Tinggong","Xiaguan-Tinggong-Jiache";clustering analysis showed that five valid clusters were extracted;factor analysis extracted seven valid common factors.Conclusion The core acupoints of acupuncture and moxibustion for the treatment of TMD is Xiaguan-Hegu-Jiache-Tinggong,and mainly follows the principle of combining proximal and distal acupoints.

Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.

Purpose/Significance To design a comprehensive data platform to meet the needs of collecting and sharing survey data on meteorological sensitive diseases,so as to enhance monitoring capabilities for meteorological sensitive diseases in China.Method/Process Through various methods such as data extraction,data exchange,data import and customized collection,disease data,meteoro-logical data,environmental data and diagnosis and treatment data are processed and integrated into the platform for unified management.Result/Conclusion This platform realizes the functions of data collection,aggregation,visualization display and data sharing,which can provide support for scientific researchers in various bases across the country to better manage and utilize meteorological sensitive disease survey data.

The standardization of classification methods of Traditional Chinese Medicine(TCM) ancient books can provide a clear and reliable reference for all kinds of TCM ancient books collection units, which can also promote the sharing and utilization of TCM ancient books. We studied and investigated the classification methods of TCM ancient books in past dynasties. The standard on classification of TCM ancient books was formulated by compared with the classification table of Zhongguo Zhongyi Guji Zongmu, and referred to the classification table of Zhonghua Guji Zongmu. This standard specified three-level categories and classification principles of TCM ancient books, and mainly composed of basic categories, three-level category table, classification principles and examples, and instructions for use.