Treating chronic atrophic gastritis: identifying sub-population based on real-world TCM electronic medical records.

Background and Objective: Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method: Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion: Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

The different paradigms of NK cell death in patients with severe trauma.

Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.

Quercetin ameliorates atherosclerosis by inhibiting inflammation of vascular endothelial cells via Piezo1 channels.

BACKGROUND: Natural antioxidants, exemplified by quercetin (Qu), have been shown to exert a protective effect against atherosclerosis (AS). However, the precise pharmacological mechanisms of Qu also remain elusive. PURPOSE: Here, we aimed to uncover the anti-atherosclerotic mechanisms of Qu. METHODS/STUDY DESIGNS: The inflammatory cytokine expression, activity of NLRP3 inflammasome and NF-κB, as well as mechanically activated currents and intracellular calcium levels were measured in endothelial cells (ECs). In addition, to explore whether Qu inhibited atherosclerotic plaque formation via Piezo1 channels, Ldlr-/- and Piezo1 endothelial-specific knockout mice (Piezo1△EC) were established. RESULTS: Our findings revealed that Qu significantly inhibited Yoda1-evoked calcium response in human umbilical vein endothelial cells (HUVECs), underscoring its role as a selective modulator of Piezo1 channels. Additionally, Qu effectively reduced mechanically activated currents in HUVECs. Moreover, Qu exhibited a substantial inhibitory effect on inflammatory cytokine expression and reduced the activity of NF-κB/NLRP3 in ECs exposed to ox-LDL or mechanical stretch, and these effects remained unaffected after Piezo1 genetic depletion. Furthermore, our study demonstrated that Qu substantially reduced the formation of atherosclerotic plaques, and this effect remained consistent even after Piezo1 genetic depletion. CONCLUSION: These results collectively provide compelling evidence that Qu ameliorates atherosclerosis by inhibiting the inflammatory response in ECs by targeting Piezo1 channels. In addition, Qu modulated atherosclerosis via inhibiting Piezo1 mediated NFκB/IL-1ß and NLRP3/caspase1/ IL-1ß axis to suppress the inflammation. Overall, this study reveals the potential mechanisms by which natural antioxidants, such as Qu, protect against atherosclerosis.

[Evaluation of the clinical effect of acupuncture in treatment of neck pain in cervical spondylosis based on propensity score matching].

OBJECTIVE: To observe the clinical effect and safety of acupuncture in treatment of neck pain due to cervical spondylosis. METHODS: According to the patients' preference and acceptance for the interventions of neck pain induced by cervical spondylosis, an acupuncture group (221 cases) and a non-acupuncture group (251 cases) were divided. After the control of confounding factors with propensity score matching, 218 cases were included in either acupuncture group or non-acupuncture group. In the acupuncture group, acupuncture was applied to Dazhui (GV 14), Baihui (GV 20), ashi points, bilateral neck-Jiaji (EX-B 2), Fengchi (GB 20), Houxi (SI 3), Shenmai (BL 62), etc. The treatment was given once daily, one course of intervention was composed of 5 treatments and 3 courses were included. In the non-acupuncture group, the oral administration of imrecoxib tablets and cobalt tablets was prescribed for 2 weeks. Before and after treatment, the scores of Northwick Park questionnaire (NPQ) and the simplified McGill pain questionnaire (SF-MPQ) were observed, and the safety was assessed in patients of the two groups. RESULTS: After treatment completion, the scores of NPQ and SF-MPQ were all reduced when compared with those before treatment in each group (P<0.001), and the scores of NPQ and SF-MPQ in the acupuncture group were lower than those of the non-acupuncture group (P<0.001). The incidence of adverse reactions was 6.0% (13/218) in the acupuncture group and was 10.1% (22/218) in the non-acupuncture group, without statistical significance in comparison (P>0.05). CONCLUSION: Acupuncture is effective and safe in the relief of neck pain and the improvement of comprehensive quality of life in the patients with cervical spondylosis.

High salt induced hypertension leads to cognitive defect.

Although increasing evidences suggest a relationship between hypertension and brain function for years, it is still unclear whether hypertension constitutes a risk factor for cognitive decline and its underlying mechanism. In the present study, an experimental animal model of hypertension simply by feeding rats with high salt diet was employed. We found that long-term high salt intake caused a marked increase of systolic blood pressure linked to a declined regional cerebral blood flow. Fear conditioning and morris water maze behavioral test revealed that high salt diet induced hippocampal dependent spatial reference memory deficits, while a decreased synaptogenesis without neuronal loss in hippocampus was observed in high salt treated rats. Furthermore, we found that high salt induced a decrease of intracellular calcium, which inactivated CaMK II and resulted in dephosphorylation of CREB at Ser133. These findings suggest a novel etiopathogenic mechanism of cognitive deficit induced by hypertension, which is initiated by high salt diet.

A soluble pentacene: synthesis, EPR and electrochemical studies of 2,3,9,10-tetrakis(trimethylsilyl)pentacene.

A soluble 2,3,9,10-tetrakis(trimethylsilyl)pentacene (1) was synthesized; the discovery of the radical cationic character of in solution through EPR measurement has provided insights into the sensitivity of acenes towards light and oxygen.