Feasibility and performance of the chronic obstructive pulmonary disease population screener and chronic obstructive pulmonary disease screening questionnaire in a Chinese physical examination center.

Background: Chronic obstructive pulmonary disease (COPD) affects up to 13% of the Chinese population, though it is under diagnosed throughout China. Screening among asymptomatic individual as part of routine health checks in China can facilitate early diagnosis and intervention to prevent disease progress. The COPD Population Screener (COPD-PS) or COPD Screening Questionnaire (COPD-SQ) has yet to be applied in Chinese physical examination centers (PECs) for COPD screening, and their feasibility and effectiveness should be clarified before full-scale implementation. This study is the first to apply the COPD-PS and COPD-SQ in a public hospital PEC in China to assess their feasibility and effectiveness and to identify their optimal cutoff values. Methods: People aged ≥40 years who attended the Second Affiliated Hospital of Shantou University PECs from September 2021 to December 2022 were asked to complete the COPD-PS and COPD-SQ and to undergo spirometry. The optimal cutoff values of the two questionnaires at the maximal Youden index were found, and the sensitivity and specificity were calculated. Results: Data from 198 participants were analyzed; mean [standard deviation (SD)] age of patients was 63.52 (10.94) years. Twenty-five participants (12.63%) were diagnosed with COPD. The number of COPD patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 to 4 were 8, 12, 4, and 1, respectively. The area under the curves (AUCs) of the COPD-PS and COPD-SQ were 0.730 and 0.738, respectively. The optimal COPD-PS cutoff value of 4 points corresponded to a sensitivity of 72.00% and a specificity of 60.10%. The COPD-SQ optimal cutoff value of 15 points corresponded to a sensitivity of 76.00% and a specificity of 63.60%. Conclusions: Applying the COPD-PS and COPD-SQ in Chinese PECs is feasible, cost-effective and effective. COPD-PS and COPD-SQ can facilitate the early diagnosis of COPD, and whether they can improve the participants' quality of life would benefit a further study. It is recommended that the COPD-PS or COPD-SQ questionnaires be added to the screening of the physical examination program in PECs as part of health checks for people over 40 years old.

The blockade of the TGF-ß pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity.

TGF-ß is thought to be involved in the physiological functions of early organ development and pathological changes in substantial organ fibrosis, while studies around adipose tissue function and systemic disorders of glucolipid metabolism are still scarce. In this investigation, two animal models, aP2-SREBP-1c mice and ob/ob mice, were used. TGF-ß pathway showed up-regulated in the inguinal white adipose tissue (iWAT) of the two models. SB431542, a TGF-ß inhibitor, successfully increased inguinal white adipocyte size by more than 1.5 times and decreased the weight of Peripheral organs including liver, Spleen and Kidney to 73.05%/62.18%/73.23% of pre-administration weights. The iWAT showed elevated expression of GLUTs and lipases, followed by a recovery of circulation GLU, TG, NEFA, and GLYCEROL to the wild-type levels in aP2-SREBP-1c mice. In contrast, TGF-ß inhibition did not have similar effects on that of ob/ob mice. In vitro, TGF-ß blocker treated mature adipocytes had considerably higher levels of glycerol and triglycerides than the control group, whereas GLUTs and lipases expression levels were unchanged. These findings show that inhibiting the abnormally upregulated TGF-ß pathway will only restore iWAT expansion and ameliorate the global metabolic malfunction of glucose and lipids in lipodystrophy, not obesity.

IGHG1 promotes malignant progression in breast cancer cells through the regulation of AKT and VEGF signaling.

Immunoglobulin heavy constant chain gamma 1 (IGHG1) is highly expressed in a variety of cancers and is considered an emerging prognostic marker. Overexpression of IGHG1 in breast cancer tissues has also been demonstrated, but an in-depth analysis of its role in disease progression has not been explored. In this study, we used a range of molecular and cell-based assays to show that increased expression of IGHG1 in breast cancer cells activates AKT and vascular endothelial growth factor (VEGF) signaling, leading to enhanced cell proliferation, invasion, and angiogenesis. We further showed that IGHG1-silencing can suppress the neoplastic characteristics of breast cancer cells in vitro and suppresses tumor growth in nude mice. These data reveal a key role of IGHG1 in the malignant progression of breast cancer cells and highlight its potential as a prognostic marker and therapeutic target to control metastasis and angiogenesis in malignant breast tissue.

A novel senescence-related lncRNA signature that predicts prognosis and the tumor microenvironment in patients with lung adenocarcinoma.

Background: Cellular senescence has recently been considered a new cancer hallmark. However, the factors regulating cellular senescence have not been well characterized. The aim of this study is to identify long non-coding RNAs (lncRNAs) associated with senescence and prognosis in patients with lung adenocarcinoma (LUAD). Methods: Using RNA sequence data from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) and senescence genes from the CellAge database, a subset of senescence-related lncRNAs was first identified. Then, using univariate and multivariate Cox regression analyses, a senescence lncRNA signature (LUADSenLncSig) associated with LUAD prognosis was developed. Based on the median LUADSenLncSig risk score, LUAD patients were divided into high-risk and low-risk groups. Kaplan-Meier analysis was used to compare the overall survival (OS) in the high- and low-risk score subgroups. Differences in Gene Set Enrichment Analysis (GSEA), immune infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) module score, chemotherapy, and targeted therapy selection were also compared between the high-risk and low-risk groups. Results: A prognostic risk model was obtained consisting of the following nine senescence-related lncRNAs: LINC01116, AC005838.2, SH3PXD2A-AS1, VIMS-AS1, SH3BP5-AS1, AC092279.1, AC026355.1, AC027020.2, and LINC00996. The LUADSenLncSig high-risk group was associated with poor OS (hazard ratio = 1.17, 95% confidence interval = 1.102-1.242; p < 0.001). The accuracy of the model was further supported based on receiver operating characteristic (ROC), principal component analysis (PCA), and internal validation cohorts. In addition, a nomogram was developed consisting of LUADSenLncSig for LUAD prognosis, which is consistent with the actual probability of OS. Furthermore, immune infiltration analysis showed the low-risk group had a stronger anti-tumor immune response in the tumor microenvironment. Notably, the levels of immune checkpoint genes such as CTLA-4, PDCD-1, and CD274, and the TIDE scores were significantly higher in the low-risk subgroups than in high-risk subgroups (p < 0.001). This finding indicates the LUADSenLncSig can potentially predict immunotherapy efficacy. Conclusion: In this study, a lncRNA signature, LUADSenLncSig, that has dual functions of senescence phenotype identification and prognostic prediction as well as the potential to predict the LUAD response to immunotherapy was developed.