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

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.

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.

ObjectiveTo systematically collect， analyze， and evaluate the randomized controlled trials （RCT） of Chinese patent medicine combined with western medicine in the treatment of hypertension， map the evidence， and provide reference for the future clinical research and formulation of guidelines and policies. MethodThe relevant articles were retrieved from China Biology Medicine disc， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， PubMed， Embase， and Cochrane Library with the time interval from inception to December 31， 2022. The RCT of Chinese patent medicines combined with western medicine in the treatment of hypertension were included. The research characteristics and methodological quality were analyzed and evaluated. ResultA total of 330 RCTs of treating hypertension with Chinese patent medicines combined with Western medicine were included in this study， all of which were published in Chinese. These RCTs involved 88 Chinese patent medicines and 37 788 patients， and 46% of RCT had the sample size ≥100 patients. Eighty-seven percent of RCT showed the study period within 3 months. All the interventions in the RCTs were Chinese patent medicine + western medicine vs western medicine. Among the evaluation indicators， blood pressure， response rate， TCM syndrome score， endothelial cell function， and safety were mainly concerned. In terms of methodological quality， most articles did not mention the generation of random sequences， allocation concealment， or blinding method. The blinding evaluation of outcomes showed low risks of bias， and there was insufficient information to judge whether there was selective bias or other bias. ConclusionThere were many Chinese patent medicines used in combination with western medicine in the treatment of hypertension， and they were mainly taken orally. The existing RCT had problems such as small sample size， unclear clinical value positioning， imperfect design failing to reflect the value of Chinese patent medicines， unreasonable measurement indicators， and non-standard measurement methods. Future research should solve the above problems， improve the research quality， value， and authenticity， and enhance the reliability and extension of evidence.

Chaihu Guizhi Ganjiangtang with a definite clinical effect has been widely used and recorded since the Han Dynasty. As a classic prescription of Chaihu classic formula praised by doctors ofsuccessive generations， it has been included in the Ancient Classic Prescription Catalogue （Second Batch）： Han Medicine published by the National Administration of Traditional Chinese Medicine in August 2023. We carried out a bibliometric study involved 34 ancient books of traditional Chinese medicine， with 37 records including the name and composition of the prescription. This paper summarizes the source name， composition， original medicinal plant， dose， preparation method， usage， ancient and modern indications， and clinical application of Chaihu Guizhi Ganjiangtang. The results of textual research show that Chaihu Guizhi Ganjiangtang is derived from the Treatise on Febrile Diseases （Shanghanlun） written by ZHANG Zhongjing in the Han dynasty， and the original plants of medicines in this prescription are basically the same in ancient and modern times. Most records about the doses in ancient books are consistent with those in the Treatise on Febrile Diseases （Shanghanlun）. The efficacy of Chaihu Guizhi Ganjiangtang is to harmonize lesser yang and resolve water retention by warming. This prescription was used to treat a variety of diseases， especially those caused by disturbance of Qi movement in the greater Yang and lesser Yang. It is now mainly used to treat the diseases in the digestive system， respiratory system， dermatology， nervous system， etc.， being effective for difficult and complicated diseases. Through the excavation and combing of the ancient records of Chaihu Guizhi Ganjiangtang， this paper clarifies the key information， providing a reference for the clinical application of classical prescriptions and the development of new drugs.

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.