Objective To identify immune cell-related biomarkers in lung adenocarcinoma (LUAD) using weighted gene co-expression network analysis (WGCNA). Methods Based on data from The Cancer Genome Atlas (TCGA) database, a gene co-expression network was constructed for the TCGA-LUAD dataset using the "WGCNA" R package, and genes were clustered into different modules. Concurrently, the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm was applied to the tumor samples in the TCGA-LUAD dataset. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to evaluate the biological functions of genes within the most significantly correlated module. Candidate hub genes from the key module were intersected with a protein-protein interaction (PPI) network to identify the final hub genes. The prognostic performance of these hub genes and their correlation with immune cell infiltration were validated using Kaplan-Meier curves and the Tumor IMmune Estimation Resource (TIMER) algorithm. Finally, a multivariate Cox regression analysis was conducted on the identified hub genes to construct a prognostic risk model. Results In the co-expression network, the brown module was found to be highly correlated with the ImmuneScore, StromalScore, and ESTIMATE Score. Five immune-related hub genes were identified: CD53, PLEK, SPI1, IL10RA, and C3AR1. Enrichment analysis of the brown module revealed that its genes were primarily enriched in GO terms such as "regulation of innate immune response" and KEGG pathways like the "NF-kappa B signaling pathway". Furthermore, the expression levels of these five hub genes were significantly and positively correlated with the infiltration abundance of various immune cells. The immune relevance of the model was validated by the Immunophenoscore (IPS) and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Moreover, the established RiskScore demonstrated significant potential in predicting the response to immunotherapy. Conclusion These five immune-related key genes may serve as novel and effective potential therapeutic targets for LUAD immunotherapy, facilitating the development of personalized diagnosis and treatment strategies for patients with LUAD.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

Objective:To investigate the relationship between lumbar disc herniation and vertebral bone mineral density(BMD)of quantitative analysis of computed tomography(CT).Methods:Eighty patients with lumbar disc herniation who admitted to Beijing Tongzhou District Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to June 2024 were included in the case group,and 30 healthy volunteers who underwent physical examination in hospital were included in the healthy control group during the same period.The vertebral BMD of all subjects was quantitatively analyzed by CT.The data,lumbar BMD value,lumbar bone mass loss and osteoporosis distribution of the two groups were compared at baseline.Results:There were no significant differences in gender,age,body mass index(BMI)and abdominal circumference of baseline data between the case group and the healthy control group(P>0.05).The BMD value of the fourth lumbar vertebra(L4)in the case group was lower than that in the healthy control group,and the difference was statistically significant(t=1.991,P<0.05).There were no significant differences in BMD value and mean BMD(Lmean BMD)of the fifth lumbar vertebra(L5)between the case group and the healthy control group(P>0.05).There was no statistically significant difference in the lumbar BMD value of healthy control group between different genders(P>0.05),and there was significant difference in Lmean BMD between different genders in the case group(t=2.063,P<0.05),while there were no statistically significant difference in the L4 BMD and L5 BMD of the case group between different genders(P>0.05).The difference of Lmean BMD values of the persons with same gender(male,female)between the case group and the healthy control group were statistically significant(t=2.570,3.300,P<0.05).The ratio of normal lumbar bone mass in the case group was 48.75%,which was lower than that in the healthy control group(70.00%),and the difference was statistically significant(x2=3.974,P<0.05).The ratio of osteoporosis in the case group was 18.75%,which was higher than that in the healthy control group(3.33%),and the difference of that between two groups was significant(x2=4.172,P<0.05).There was no significant difference in the ratio of bone mass loss between the two groups(P>0.05).Conclusion:CT quantitative analysis shows that the vertebral BMD value of the patients with lumbar disc herniation is significantly lower than that of persons of the healthy control group,which indicates that the decrease of BMD value might be related to the occurrence of lumbar disc herniation.

Objective:To evaluate the clinical features of dystonia in patients with different types of atypical Parkinson syndrome (APS).Methods:A total of 104 patients with APS admitted in the Department of Neurology, Beijing Hospital from January 2015 to June 2023 were enrolled in the study, including 57 cases of multiple system atrophy (MSA), 38 cases of progressive supranuclear palsy (PSP) and 9 cases of corticobasal degeneration (CBD). Among 104 cases there were 63 males (60.6%), the mean age of patients was (62.3±8.9) years (54 to 73 years). The sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopa therapy, numbers of Hoehn & Yahr scale≥3 after 3 years of disease, and MRI findings were documented in patients with different type APS.Results:The overall frequency of dystonia in this series was 45.2%(47/104), and 33.3% (19/57) for MSA group, 50.0% (19/38) for PSP group, 9/9 for CBD group. The types of dystonia were anterocollis, retrocollis, blepharospasm, oromandibular, foot/limb dystonia, Pisa syndrome and myoclonus. In all 47 cases presenting dydtonia, dystonia was not the first complaint and it did not respond to levodopa therapy.Conclusion:In this series of atypical Parkinson syndrome, dystonia is a common feature of the disease, while it is not the first symptom at disease onset, and usually does not respond to levodopa therapy.

Objective:To investigate the relationship between lumbar disc herniation and vertebral bone mineral density(BMD)of quantitative analysis of computed tomography(CT).Methods:Eighty patients with lumbar disc herniation who admitted to Beijing Tongzhou District Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to June 2024 were included in the case group,and 30 healthy volunteers who underwent physical examination in hospital were included in the healthy control group during the same period.The vertebral BMD of all subjects was quantitatively analyzed by CT.The data,lumbar BMD value,lumbar bone mass loss and osteoporosis distribution of the two groups were compared at baseline.Results:There were no significant differences in gender,age,body mass index(BMI)and abdominal circumference of baseline data between the case group and the healthy control group(P>0.05).The BMD value of the fourth lumbar vertebra(L4)in the case group was lower than that in the healthy control group,and the difference was statistically significant(t=1.991,P<0.05).There were no significant differences in BMD value and mean BMD(Lmean BMD)of the fifth lumbar vertebra(L5)between the case group and the healthy control group(P>0.05).There was no statistically significant difference in the lumbar BMD value of healthy control group between different genders(P>0.05),and there was significant difference in Lmean BMD between different genders in the case group(t=2.063,P<0.05),while there were no statistically significant difference in the L4 BMD and L5 BMD of the case group between different genders(P>0.05).The difference of Lmean BMD values of the persons with same gender(male,female)between the case group and the healthy control group were statistically significant(t=2.570,3.300,P<0.05).The ratio of normal lumbar bone mass in the case group was 48.75%,which was lower than that in the healthy control group(70.00%),and the difference was statistically significant(x2=3.974,P<0.05).The ratio of osteoporosis in the case group was 18.75%,which was higher than that in the healthy control group(3.33%),and the difference of that between two groups was significant(x2=4.172,P<0.05).There was no significant difference in the ratio of bone mass loss between the two groups(P>0.05).Conclusion:CT quantitative analysis shows that the vertebral BMD value of the patients with lumbar disc herniation is significantly lower than that of persons of the healthy control group,which indicates that the decrease of BMD value might be related to the occurrence of lumbar disc herniation.

Objective:To evaluate the clinical features of dystonia in patients with different types of atypical Parkinson syndrome (APS).Methods:A total of 104 patients with APS admitted in the Department of Neurology, Beijing Hospital from January 2015 to June 2023 were enrolled in the study, including 57 cases of multiple system atrophy (MSA), 38 cases of progressive supranuclear palsy (PSP) and 9 cases of corticobasal degeneration (CBD). Among 104 cases there were 63 males (60.6%), the mean age of patients was (62.3±8.9) years (54 to 73 years). The sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopa therapy, numbers of Hoehn & Yahr scale≥3 after 3 years of disease, and MRI findings were documented in patients with different type APS.Results:The overall frequency of dystonia in this series was 45.2%(47/104), and 33.3% (19/57) for MSA group, 50.0% (19/38) for PSP group, 9/9 for CBD group. The types of dystonia were anterocollis, retrocollis, blepharospasm, oromandibular, foot/limb dystonia, Pisa syndrome and myoclonus. In all 47 cases presenting dydtonia, dystonia was not the first complaint and it did not respond to levodopa therapy.Conclusion:In this series of atypical Parkinson syndrome, dystonia is a common feature of the disease, while it is not the first symptom at disease onset, and usually does not respond to levodopa therapy.

Objective To explore the role and mechanism of phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin kinase(PI3K/AKT/mTOR)signaling in autoimmune thyroiditis(AIT).Methods 24 female C57BL/6 mice were randomly divided into four groups:a normal control(NC)group,an experimental autoimmune thyroiditis(EAT)group,and two groups treated with LY294002(25 mg/kg or 50 mg/kg LY294002).The degree of thyroiditis was observed by hematoxylin and eosin staining.The percentage of Th 17 cells in the spleen mononuclear cells(SMCs)was determined by flow cytometry.Enzyme-linked immunosorbent assay was used to measure the concentrations of thyroglobulin antibody(TgAb)and interleukin-17A(IL-17A)in the serum.Western blotting was conducted to detect the protein levels of IL-17A,p-AKT(Thr308),p-AKT(Ser473),p-mTOR(Ser2448),S6K1,and S6K2 in the different groups.Results Compared with the NC group,the infiltration of Th17 cells and the expressions ofIL-17A,p-AKT(Ser473),p-AKT(Thr308),p-mTOR(Ser2448),S6K1,and S6K2 rose remarkably in EAT mice.After the PI3K pathway was blocked,the degree of thyroiditis was significantly alleviated,followed by the proportion of Th17 cells,and the expression of IL-17A and PI3K pathway-related molecules decreased in a dose-dependent manner.Conclusion PI3K/AKT/mTOR signaling pathway participates in thyroid autoimmune jnjury of EAT mice by regulating Th17 cells differentiation.

Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82％and 75.64％,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95％CI:0.741-0.889)and 0.767(95％CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.