Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

Conjugated oligomers,as analogues of conjugated polymers,allow for constructing ultrafine fluorescent nanoparticles with improved sensing sensitivity due to their more precisely defined molecular structure and smaller size.Herein,a new porphyrin-pyridyl conjugated oligomer,i.e.,Zn-TPP-OMe,was designed and synthesized via Sonogashira coupling strategy and a super-small(～2.0 nm)water-soluble fluorescent nanoprobe(Zn-TPP-OMe nanoparticles(NPs))was subsequent obtained by nanoprecipitation method.Due to the addition reaction of chlorine atom to porphyrin ring,the fluorescence intensity of Zn-TPP-OMe NPs at 619-660 nm significantly decreased with increasing HCLO concentration.Meanwhile,Zn-TPP-OMe NPs aggregated obviously after adding HClO,achieving enhanced fluorescence quenching.The fluorescence detection mechanism was verified by transmission electron microscopy(TEM),proton nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS)analyses.The experimental results indicated that the porphyrin-pyridyl conjugated oligomer nanosystem had high sensitivity(LOD=0.005 μmol/L)and excellent selectivity in detection of HClO,and was successfully applied to the sensing of HClO in actual water samples.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin. METHODS: Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×10⁹/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes and hemoglobin. RESULTS: The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717). CONCLUSION CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.
Male ; Humans ; Altitude Sickness/metabolism* ; Glucose Transporter Type 1 ; 2,3-Diphosphoglycerate ; Hemoglobins ; Chronic Disease ; RNA, Messenger ; Phenotype ; Glucose

Objective:To analyze influencing factors of coronary heart disease(CHD)in advanced aged population and the therapeutic effect of percutaneous coronary intervention(PCI).Methods:According to diagnosed as CHD or not,a total of 209 aged patients underwent cardio-and cerebrovascular examination in our hospital were divided into CHD group(n=104)and no CHD group(n=105),and general clinical data were compared between two groups.According to treatment method,CHD group was divided into routine treatment group(received routine medication)and PCI group;and recovery time,hospital stay,incidence rate of adverse events during admission and prognosis within one-year follow-up were compared between two groups.Influencing factors of CHD in aged population was analyzed.Results:Compared with no CHD group,there were significant rise in percentages of age＞80 years,smoking,diabetes mellitus,hypertension,total cholesterol＞5.17mmol/L,triglyceride＞1.7mmol/L,high density lipoprotein cholesterol(HDL-C)＜0.96mmol/L,low density lipoprotein cholesterol＞3.37mmol/L,uric acid＞420μmol/L and fibrinogen＞4 g/L in CHD group(P＜0.05 or＜0.01).Compared with routine treat-ment group,there were significant reductions in recovery time,hospital stay,incidence rates of adverse events,lu-men loss/restenosis,primary and secondary endpoint events within one-year follow-up in PCI group(P＜0.05 or＜0.01).Binary Logistic regression analysis indicated that age＞80 years,uric acid＞420μmol/L and HDL-C＜0.96mmol/L were independent risk factors for CHD in advanced aged population(OR=1.755～6.103,P＜0.05 or＜0.01).Conclusion:Age＞80 years,uric acid＞420μmol/L and HDL-C＜0.96 mmol/L are independent risk fac-tors for coronary heart disease in advanced aged population.PCI can significantly shorten recovery time and treat-ment time in advanced aged patients with coronary heart disease with good safety.

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H₂O₂. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.
Animals ; Harmaline/metabolism* ; Harmine/metabolism* ; Heme ; Hydrogen Peroxide ; Rats ; Tandem Mass Spectrometry

Objective To investigate the effects of microRNA( miR)-29a-3p on the proliferation and invasion of gastric cancer cells and analyze its related molecular mechanism. Methods The expression level of miR-29a-3p in gastric cancer cells was detected, and the role of miR-29a-3p in the proliferation, migration, and invasion of gastric cancer cells was evaluated. Western blotting and luciferase analysis showed that miR-29a-3p was directly bound to Serpinhl 3 ' -untranslated region(3' UTR). In addition, the effects of the miR-29a-3p/Serpinhl axis on the proliferation, migration, and invasion of gastric cancer cells were detected by MTT assay, colony formation assay, and Transwell assay in vitro. Results After transfection, the expression of miR-29a-3p in the miR-29a-3p mimic group was significantly higher than that in the miR-29a-3p negative control and blank group. After transfection, the proliferation of BGC823 cells decreased significantly. Luciferase analysis showed that miR-29a-3p inhibited the expression of Serpinhl by targeting the 3 ' UTR of Serpinhl. In addition, overexpression of miR-29a-3p significantly inhibited the proliferation, invasion, and migration of gastric cancer cells by targeting Serpinhl. Conclusion MiR-29a-3p can target Serpinhl and regulate the proliferation and invasion of gastric cancer cells.

OBJECTIVE: To investigate the prognostic value of interim ¹⁸F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (△SUVmax%) cut-off value. The prognostic value of △SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum △SUV max% cut-off value was 74.9%. Patients with △SUVmax%≥74.9% had a lower rate of progression or recurrence than those with △SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). △SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). △SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), △SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that △SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION Both 5-PS and △SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of △SUVmax% is superior to that of 5-PS.
Fluorodeoxyglucose F18/therapeutic use* ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Thiamine

Objective: To evaluate the diagnostic value and application of 24 h multichannel intraluminal impedance-pH (24 h MII-pH) monitoring in children with gastroesophageal reflux disease (GERD). Methods: This is a cross-sectional study. From January 2013 to December, 2020, 417 patients who received 24 h MII-pH monitoring in Department of Gastroenterology of Children's Hospital Capital Institute of Pediatrics were included. According to results, these children were divided into the GERD and non-GERD groups. Furthermore, the 132 children with GERD who had gastroscopy were divided into the reflux esophagitis (RE) and non-erosive reflux disease (NE) groups to investigate the differences in their refluxes. Non-parametric Mann-Whitney U test or indepentent sample t test was used for comparisons between the groups. Results: Among the 417 children, 232 were males and 185 females, aged (7.3±3.9) years. The course of disease was 0.5 (0.1, 2.0) years. The main clinical symptoms included acid reflux (128 cases), vomiting (173 cases), abdominal pain (101 cases), and cough (76 cases). The 24 h MII-pH monitoring were positive in 243 children (58.3%, 243/417), which was higher than that by 24 h esophageal pH monitoring (43.6%, 182/417). The 24 h MII-pH monitoring results demonstrated significant differences in the episodes of acid reflux, weakly acidic reflux, non-acidic reflux, liquid reflux and mixed reflux between GERD and non-GERD groups (10 (4, 19) vs. 4 (1, 9) times/24 h, 14 (6, 32) vs. 7 (3, 13) times/24 h, 0 (0, 0) vs. 0 (0, 0) times/24 h, 19 (10, 34) vs. 8 (3, 14) times/24 h, and 6 (2, 12) vs. 3 (1, 5) times/24 h, Z=-6.96, -7.25, -5.62, -8.75, and -6.48, all P<0.05, respectively). Besides, the results also showed significant differences in Boix-Ochoa score, episodes of long reflux, course of long reflux, and episodes of weakly acidic reflux between the RE and NE groups (51.2 (21.4, 153.2) vs. 20.7 (12.1, 34.7), 5 (2, 10) vs. 1 (0, 4) times/24 h, 19 (7, 87) vs. 8 (3, 22) min, and 5 (2, 15) vs. 15 (6, 33) times/24 h, Z=-3.44, -3.41, -2.65, and -2.27, all P<0.05, respectively). Conclusion: 24 h MII-pH monitoring not only improves the detection rate of GERD in children, but also provides a possibility to early etiological diagnosis.
Female ; Male ; Humans ; Child ; Cross-Sectional Studies ; Electric Impedance ; Gastroesophageal Reflux/diagnosis* ; Esophageal pH Monitoring ; Hydrogen-Ion Concentration