ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Objective:To analyze the patterns of change of brain function among civil pilots in prospective memory tasks by using task-state functional magnetic resonance imaging (fMRI) and a cue-based repetitive search task.Methods:A total of 85 subjects were enrolled, including 47 civil pilots (pilot group) and 38 ordinary workers (control group). The task-state fMRI data during the execution of the prospective memory task was analyzed using a general linear model to find out about the activation patterns of brain functions in the 2 groups in the 3 phases of encoding, maintenance, and retrieval of the prospective memory task. The differences in activation patterns between the 2 groups and correlations between regions of interest and the rate of accuracy, reaction time and flying hours were analyzed.Results:The repeated measurement analysis of variance showed that there were no interactions of reaction time or of the rate of accuracy between the task and grouping ( P>0.05), and that the difference in the main effect of grouping was significant ( F=5.67, 15.46, P=0.020, <0.001). The difference in the main effect of grouping on the rate of accuracy was significant ( F=5.42, P=0.022), and the rate of accuracy in the pilot group was higher than in the control group ( P=0.048). In the phase of encoding, the activation in the bilateral cerebellum, bilateral superior frontal gyrus, bilateral fusiform gyrus, and temporal lobe regions decreased in the pilot group compared with the control group ( t=2.68-4.13, all P<0.05), while the activation in the fusiform gyrus and the right parietal superior gyrus increased, and the differences were statistically significant ( t=3.28, 3.35, 3.02, P=0.038, 0.024, 0.042). During the phase of maintenance, the pilot group showed significantly reduced activation in the bilateral cerebellum, bilateral medial superior frontal gyrus, bilateral middle occipital gyri, and the right middle temporal gyrus compared with the control group ( t=2.24-3.36, P<0.05 or 0.01). In the retrieval phase, activation in the right peri-calcarine cortex, bilateral caudate nuclei, and bilateral precentral and postcentral gyri was enhanced in the pilot group compared with the control group ( t=2.57-3.35, all P<0.05), especially in the right middle frontal gyrus ( t=3.12, P=0.007). In the encoding phase, activation was increased in the left fusiform gyrus and right parietal superior gyrus of the pilot group, which was positively correlated with flying hours in the last 3 months ( r=0.347, 0.418, P=0.020, 0.005). Conclusions:Due to long-term flights, the way in which such regions as the frontal lobe, cerebellum, and default mode network are activated in civil pilots is likely to undergo some changes during prospective memory activities, which is why they have higher processing efficiency when performing prospective memory tasks.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Objective:To analyze the patterns of change of brain function among civil pilots in prospective memory tasks by using task-state functional magnetic resonance imaging (fMRI) and a cue-based repetitive search task.Methods:A total of 85 subjects were enrolled, including 47 civil pilots (pilot group) and 38 ordinary workers (control group). The task-state fMRI data during the execution of the prospective memory task was analyzed using a general linear model to find out about the activation patterns of brain functions in the 2 groups in the 3 phases of encoding, maintenance, and retrieval of the prospective memory task. The differences in activation patterns between the 2 groups and correlations between regions of interest and the rate of accuracy, reaction time and flying hours were analyzed.Results:The repeated measurement analysis of variance showed that there were no interactions of reaction time or of the rate of accuracy between the task and grouping ( P>0.05), and that the difference in the main effect of grouping was significant ( F=5.67, 15.46, P=0.020, <0.001). The difference in the main effect of grouping on the rate of accuracy was significant ( F=5.42, P=0.022), and the rate of accuracy in the pilot group was higher than in the control group ( P=0.048). In the phase of encoding, the activation in the bilateral cerebellum, bilateral superior frontal gyrus, bilateral fusiform gyrus, and temporal lobe regions decreased in the pilot group compared with the control group ( t=2.68-4.13, all P<0.05), while the activation in the fusiform gyrus and the right parietal superior gyrus increased, and the differences were statistically significant ( t=3.28, 3.35, 3.02, P=0.038, 0.024, 0.042). During the phase of maintenance, the pilot group showed significantly reduced activation in the bilateral cerebellum, bilateral medial superior frontal gyrus, bilateral middle occipital gyri, and the right middle temporal gyrus compared with the control group ( t=2.24-3.36, P<0.05 or 0.01). In the retrieval phase, activation in the right peri-calcarine cortex, bilateral caudate nuclei, and bilateral precentral and postcentral gyri was enhanced in the pilot group compared with the control group ( t=2.57-3.35, all P<0.05), especially in the right middle frontal gyrus ( t=3.12, P=0.007). In the encoding phase, activation was increased in the left fusiform gyrus and right parietal superior gyrus of the pilot group, which was positively correlated with flying hours in the last 3 months ( r=0.347, 0.418, P=0.020, 0.005). Conclusions:Due to long-term flights, the way in which such regions as the frontal lobe, cerebellum, and default mode network are activated in civil pilots is likely to undergo some changes during prospective memory activities, which is why they have higher processing efficiency when performing prospective memory tasks.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Inflammatory bowel disease (IBD) is a chronic non ‑ specific intestinal inflammatory disease. Spondyloarthritis (SpA) is a chronic inflammatory disease that occurs in the axial skeleton and surrounding joints, and is one of the most common extraintestinal manifestations of IBD. The main pathophysiologic mechanism of IBD accompanied with SpA involves the "gut‑joint axis" hypothesis, and dysbiosis of gut flora plays a key role in explaining the pathologic connection of the "gut‑joint axis" in patients with IBD accompanied with SpA. This article reviewed the progress of research on gut flora and IBD accompanied with SpA.