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 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.

Objective:To investigate the effects of baicalein on the protein kinase B(AKT)/glycogen synthase kinase 3β(GSK3β)pathway and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)in lipopolysaccharide(LPS)-activated BV2 microglial cells.Methods:BV2 microglial cells were cultured and divided into control group,LPS-induced group,and LPS+Baicalein group.Molecular docking was conducted to verify the bind-ing affinity of baicalein to AKT.Western blot and immunofluorescence staining were used to assess the expression and phosphorylation levels of AKT,GSK3β,TNF-α,and IL-1β in activated BV2 cells.Results:Baicalein exhibited a strong binding affinity for AKT.Western blot results showed that LPS stimulation led to increased TNF-α and IL-1 βexpression and decreased phosphorylation of AKT and GSK3β in BV2 cells(P＜0.05).After Baicalein treatment,TNF-α and IL-1 β expression significantly decreased,while AKT and GSK3β phosphorylation levels increased compared to the LPS group(P＜0.05).Immunofluorescence staining results were consistent with those of Western blot.Conclusion:Baicalein inhibits the expression of TNF-α and IL-1 β in activated microglia,potentially through activation of the AKT/GSK3β pathway.

Objective:To investigate the effects of baicalein on the protein kinase B(AKT)/glycogen synthase kinase 3β(GSK3β)pathway and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)in lipopolysaccharide(LPS)-activated BV2 microglial cells.Methods:BV2 microglial cells were cultured and divided into control group,LPS-induced group,and LPS+Baicalein group.Molecular docking was conducted to verify the bind-ing affinity of baicalein to AKT.Western blot and immunofluorescence staining were used to assess the expression and phosphorylation levels of AKT,GSK3β,TNF-α,and IL-1β in activated BV2 cells.Results:Baicalein exhibited a strong binding affinity for AKT.Western blot results showed that LPS stimulation led to increased TNF-α and IL-1 βexpression and decreased phosphorylation of AKT and GSK3β in BV2 cells(P＜0.05).After Baicalein treatment,TNF-α and IL-1 β expression significantly decreased,while AKT and GSK3β phosphorylation levels increased compared to the LPS group(P＜0.05).Immunofluorescence staining results were consistent with those of Western blot.Conclusion:Baicalein inhibits the expression of TNF-α and IL-1 β in activated microglia,potentially through activation of the AKT/GSK3β pathway.

Purpose/Significance To propose data governance and fusion technologies for different business application scenarios for the fusion of multi-source and multi-dimensional big data with complex sources and diverse standards.Method/Process Taking the practice of multi-source and multi-dimensional big data fusion in responding to major public health emergencies as an example,the pa-per focuses on the challenges faced by multi-source and multi-dimensional big data fusion,the design of the application architecture,technology integration,the implementation path,the application scenarios,etc.,and analyzes the application effect and the deficiencies that exist.Result/Conclusion Through the design of intelligent multi-source and multi-dimensional big data fusion technology,real-time monitoring,reading,governance,and interactive correlation of high-frequency updates at 100 billion levels are realized,and intel-ligent paths are explored for effectively responding to public emergencies.

In order to solve the problem of strong subjectivity and difficulty in quantification,clinical objectification mainly adopts the techniques of image processing,computer vision and machine learning.The acquisition and processing of prior knowledge is a key link in the objectification of inspection,as well as an important elaboration of the quantification of subjective judgment and macro performance in objectification research.However,there is still a lack of in-depth summary and parametric processing of prior knowledge.Based on the analysis of the current research status of objectification of inspection,this paper uses data mining technology to summarize the experience of TCM inspection.Moreover,the observation information can be transformed into quantifiable digital features through natural language processing and representation learning.Meanwhile,the application of deep learning can realize automatic diagnosis and analysis of observation images to improve accuracy and efficiency,and promote the process of TCM modernization.

Objective To investigate the infection of Chlamydia pneumoniae and mycoplasma pneumoniae in adults and their association with atherosclerosis,and to provide theoretical guidance for the prevention of such diseases. Methods A case-control study was used to collect 362 patients who were diagnosed with atherosclerosis from January 2019 to December 2021 in Department of Sichuan Bazhong Central Hospital, and 370 cases who were admitted to the hospital during the same period of physical examination without any cardiovascular disease were selected as the control group, and whole blood samples of the two groups of study subjects were collected, and the infection of Chlamydia pneumoniae and mycoplasma pneumoniae was detected by PCR. Results The infection rate of Chlamydia pneumoniae was 35.49%, the infection rate of mycoplasma was 40.37%, and the co-infection rate was 11.37%；The infection rate of Chlamydia pneumoniae in the control group was 12.04%, the infection rate of mycoplasma was 15.83%, and the coinfection rate was 3.14%, and the difference between the two groups was statistically significant ( χ²=10.926, P=0.023). The effects of mycoplasma, chlamydia, and co-infection on atherosclerotic patients have sex differences, mainly manifested as higher infection rates in men; In addition, the effects of mycoplasma, chlamydia, and co-infection on atherosclerosis patients varied by age, mainly in the 55-70 years age group (P<0.05). Multivariate logistic regression results showed that Chlamydia pneumoniae infection was a risk factor for atherosclerosis (OR=1.303, 95%CI: 1.043-1.677) in the whole population, and chlamydia pneumoniae (OR=1.472, 95% CI: 1.037-1.556), mycoplasma (OR=2.003, 95%CI: 1.637-3.842) and co-infection in men (OR=1.937, 95%CI: 1.380-2.184) were risk factors for atherosclerosis, while co-infection in women (OR=1.699, 95%CI: 1.263-1.765) was a risk factor for atherosclerosis. Conclusion Chlamydia pneumoniae and mycoplasma infection are risk factors for atherosclerosis, and their impact on male groups is greater, and more attention needs to be paid to them.

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.