BACKGROUND:Diabetic kidney disease (DKD) is a major cause of renal failure and end-stage renal disease. Pyroptosis, a Gasdermin-dependent inflammatory form of programmed cell death, has been implicated in DKD progression. Metformin has shown renoprotective effects in DKD; however, the underlying mechanisms remain unclear. OBJECTIVE:To investigate whether metformin attenuates high glucose-induced pyroptosis and inflammatory responses in HK-2 cells through SIRT1-mediated regulation of the TXNIP/NLRP3 pathway. METHODS:Bioinformatics analyses were performed to identify DKD-related pyroptosis-associated genes and enriched pathways. Serum TXNIP and IL-1β levels were measured in patients with type 2 diabetes mellitus stratified by urinary albumin-to-creatinine ratio (UACR). HK-2 cells were exposed to high glucose (30 mM) to establish an in vitro injury model. Oxidative stress, pyroptosis-related signalling and inflammatory cytokines were evaluated using molecular and immunological assays. SIRT1 modulation and TXNIP silencing were used to investigate pathway regulation. Chromatin immunoprecipitation assays were performed to assess SIRT1 occupancy and histone acetylation status within the TXNIP promoter region. RESULTS:Pyroptosis-related genes were mainly enriched in inflammatory and NLRP3 inflammasome-associated pathways. Serum TXNIP and IL-1β levels were elevated in DKD patients and positively correlated with UACR. In HK-2 cells, high glucose reduced SIRT1 expression and activated the TXNIP/NLRP3 inflammasome pathway, accompanied by increased GSDMD cleavage and inflammatory cytokine expression. Metformin partially reversed these changes. Altered SIRT1 activity was also associated with changes in H3K56 acetylation enrichment within the TXNIP promoter region. CONCLUSION:Metformin may alleviate high glucose-induced pyroptosis and inflammatory responses in HK-2 cells, potentially through modulation of SIRT1-associated TXNIP/NLRP3 signalling and TXNIP-related chromatin acetylation status.

Diabetes mellitus and its complications are chronic inflammatory diseases driven by metabolic stress. PANoptosis is a recently defined inflammatory lytic cell death pathway that integrates key features of pyroptosis, apoptosis, and necroptosis, and is orchestrated by the PANoptosome complex. Emerging evidence indicates that PANoptosis plays a critical role in the pathogenesis of diabetic complications, prominently in diabetic kidney disease, retinopathy, neuropathy, and cardiomyopathy, with emerging indirect evidence from surrogate models suggesting its potential involvement in diabetic foot ulcers. In this review, we summarise the core molecular mechanisms of PANoptosis, with a focus on the crosstalk among the three programmed cell death pathways under diabetic conditions. We discuss how metabolic stressors such as hyperglycaemia, lipotoxicity, and endoplasmic reticulum stress activate distinct PANoptosome assemblies—including those involving Z-DNA-binding protein 1 (ZBP1), absent in melanoma 2 (AIM2), receptor-interacting protein kinase 1 (RIPK1), NOD-like receptor family pyrin domain-containing protein 12 (NLRP12), NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), and NOD-like receptor family CARD domain-containing protein 5 (NLRC5)—thereby linking metabolic dysregulation to inflammatory cell death. Moreover, we highlight recent advances in targeting PANoptosis as a therapeutic strategy, emphasising interventions directed at upstream metabolic triggers, PANoptosome components, and downstream effector molecules. Finally, we identify key knowledge gaps and propose future research directions to facilitate clinical translation. A deeper understanding of PANoptosis in diabetic complications may pave the way for novel therapeutic approaches that simultaneously block multiple cell death pathways to ameliorate disease progression.

Diabetes mellitus (DM) is a systemic metabolic disorder characterized by chronic hyperglycemia, which can affect the kidneys, retina, peripheral nerves, and cardiovascular system, ultimately leading to multiple chronic complications. Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor activated through canonical cleavage, such as thrombin-mediated cleavage, and non-canonical cleavage, such as cleavage by activated protein C or matrix metalloproteinase-1. These activation modes initiate diverse downstream signaling pathways, including Gαq/PLC-β/PKC, Gα12/13/Rho, and β-arrestin-dependent signaling, and contribute to inflammation, fibrosis, angiogenesis, and apoptosis. This review summarizes the role of PAR1 in the pathogenesis of type 2 diabetes mellitus (T2DM), focusing on its effects on endothelial insulin resistance, adipose tissue inflammation, and brown adipose tissue dysfunction. We further discuss the pathogenic mechanisms of PAR1 in diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy, and diabetic cardiovascular disease. This review also outlines recent advances in PAR1-targeted therapies, including orthosteric antagonists such as vorapaxar, biased signaling modulators such as 3K3A-APC and parmodulins, and intracellular inhibitors such as PZ-128. Their therapeutic potential and current challenges in antithrombotic therapy and target-organ protection are also discussed, with the aim of informing more precise strategies for preventing and treating DM and its chronic complications.

Diabetes mellitus is primarily categorized into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), which exhibit distinct pathogenic mechanisms. T1DM is characterized by an absolute deficiency of insulin secretion, predominantly resulting from the autoimmune-mediated destruction of pancreatic beta cells. In contrast, T2DM arises from a combination of insulin resistance in peripheral tissues and a compensatory insulin secretory response that ultimately becomes inadequate. The pathogenesis of diabetes mellitus is orchestrated through bidirectional crosstalk between autoimmune aggression and metabolic derangement. γδ T cells, innate-like lymphocytes bridging innate and adaptive immunity, play pivotal roles in tissue homeostasis, inflammation, and immunity through cytokine production and cytotoxicity. This review comprehensively examines the dual roles of γδ T cells across diabetes mellitus types. Furthermore, γδ T cells contribute to diabetic complications and are profoundly affected by the diabetic milieu, leading to defective anti-infection and anti-tumor immunity. We discuss emerging therapeutic strategies targeting γδ T cells or their effector pathways and highlight key knowledge gaps regarding subset-specific functions, dynamic changes during disease progression, and tissue-resident γδ T cell roles. Elucidating these mechanisms may provide a strong foundation for developing novel γδ T cell-based immunotherapies for diabetes mellitus and its complications.

The assessment of frailty status and visceral obesity, determined by chest CT measurements of low thoracic muscle mass and elevated AC, is independently correlated with an increased risk of admission to the MICU and mortality among sepsis patients with pneumonia. This underscores the significance of CT-derived body composition as a critical imaging biomarker that reflects the physiological reserve of sepsis patients and their associated risk of adverse events.

Although much research focuses on the effects of hyperglycemia during pregnancy on maternal and offspring health, this narrative review specifically centers on the role of insulin resistance (IR) in pregnancy complications and offspring long-term health. Although hyperglycemia and IR are closely intertwined, this review deliberately prioritizes IR as a distinct yet interconnected factor driving metabolic dysfunction. During pregnancy, IR naturally increases to support fetal development. However, when IR becomes excessive, it can lead to metabolic disturbances and placental dysfunction. These conditions elevate the risk of pregnancy complications, impair fetal development, and adversely affect the long-term metabolic and cognitive health of the offspring. This review explores key factors influencing pregnancy-related IR, including genetic predisposition, lifestyle, physiological adaptations, hormonal fluctuations, and gut microbiota dysbiosis. It further examines how these factors worsen maternal metabolic imbalances and contribute to adverse pregnancy outcomes, including gestational hyperglycemia and hypertensive disorders, as well as their effects on neonatal complications and the long-term health of the offspring. Notably, this review is one of the first to address the transgenerational inheritance of IR, highlighting potential mechanisms such as epigenetic modifications, mitochondrial dysfunction, and the vertical transmission of altered maternal microbiota. In addition, we outline various preventive and therapeutic strategies aimed at mitigating these issues. These strategies include lifestyle changes, pharmacological treatments, nutritional supplementation, and emerging therapies such as mitochondrial-derived peptides and adipokine inhibitors. This narrative review provides a focused perspective on how pregnancy-related IR influences maternal and offspring health, offering insights for future clinical management and research.

AIMS:To explore the interaction of TGFβ regulatory microRNAs (miRNAs) with different severities of diabetic kidney disease (DKD).METHODS:According to different UACR (30 and 300 mg/g), 436 subjects were included, and high glucose induced RMCs were cultured. Real-time PCR, ELISA, and automatic biochemical analysis were used to measure miRNAs, TGFβ1, and other biochemical indicators in serum and RMCs. Target genes of miRNA were predicted and visualised by bioinformatics.RESULTS:HbA1c, TGFβ1, miR-217, and miR-224 in T2DM patients increased with UACR, while miR-192 and miR-216a decreased. Ln UACR was positively correlated with HbA1c, TGFβ1, miR-217, and miR-224, and negatively correlated with miR-192 and miR-216a. High glucose and TGFβ1 affected miRNAs and these miRNAs affected each other. The miRNA target genes mainly revolve around PTEN, PI3K/Akt, and MAPK signalling pathways.CONCLUSION:TGFβ regulatory miRNAs and different severity of DKD have a potential interaction regulating fibrosis through PTEN, PI3K/Akt, and MAPK pathways.

Cuproptosis, a recently discovered form of cell death, stems from an overabundance of copper ions infiltrating mitochondria. These ions directly engage lipoylated proteins, prompting their oligomerization and subsequent loss of iron-sulfur clusters. This sequence induces proteotoxic stress, ultimately culminating in cell death. Type 2 diabetes, a chronic metabolic disorder resulting from a complex interplay of genetic and environmental factors, has not yet been fully understood in terms of its etiology and pathogenesis. Intricately, it is linked to various modalities of cell death, including mitochondrial autophagy, apoptosis, pyroptosis, and ferroptosis. Studies have discovered impaired copper metabolism in individuals with Type 2 diabetes, hinting at a unique role for copper homeostasis in the progression of the disease. To this end, the present research aims to delineate the potential correlation between cuproptosis and Type 2 diabetes by exhaustively reviewing the existing literature. By synthesizing relevant research on cuproptosis, the paper intends to lay the groundwork for a thorough exploration of the pathogenesis of Type 2 diabetes and the development of targeted therapeutic interventions. The ultimate objective is to facilitate a deeper understanding of Type 2 diabetes and to identify novel therapeutic strategies associated with cuproptosis.

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the “bootstrap” method. ResultsThe study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (β=.097; P<.001). There was an association between MSDP and TD (β=.074; P<.001) as well as between TD and COPD (β=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: β=.094; P<.001 and indirect: β=.004; P=.03). The indirect effect remains present in the smoking population (direct: β=.120; P<.001 and indirect: β=.002; P=.03). ConclusionsThis study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

BACKGROUND:Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms.METHODS:First, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments.RESULTS:AXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1.CONCLUSIONS:The present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.

Objective This study aimed to investigate the risk factors for peripheral arteriosclerosis (PAS) and peripheral artery disease (PAD) in chronic obstructive pulmonary disease (COPD) patients and potential ultrasound indicators that could be used to improve detection. Method Outpatients seeking care between January 1, 2017, and December 31, 2020, in The First Affiliated Hospital of China Medical University were prospectively recruited. Subjects were divided into COPD and non-COPD (control) groups, and the COPD group was further divided into PAD and non-PAD subgroup, at the same time, PAS and non-PAS subgroup. Indicators of PAD -ankle-brachial index (ABI), indicators of PAS- pulse wave velocity (PWV), and ultrasound indices -peak systolic blood flow velocity (PSV) and blood flow acceleration velocity (AccV) were compared. Result Sixty-nine (61.6%) of 112 enrolled subjects had COPD. COPD patients had higher age, and blood pressure (BP)lower than controls. Seventeen (24.6%) COPD patients had PAD, the prevalence of PAD increases with the decrease of lung function, and seven (16.3%) non-COPD patients had PAD, however, there was no significant statistical difference between COPD and non-COPD groups. Fifty (72.5%) COPD patients had PAS, and thirty-four (79.1%) non-COPD patients had PAS, however, there was also no significant difference. The PAS subgroup had higher age, body mass index(BMI), body fat percentage(BFP), lower FEV1 and FEV1/FVC, as well as higher levels of right brachial artery and left dorsalis pedis artery AccV. Factors that correlated with ABI were 6MWD, post-bronchodilator FEV1, FEV1/ FVC, and maximal middle expiratory flow between 75% and 25% of FVC. Age, BP, and 6MWD, but not pulmonary function, were associated with brachial-ankle PWV (baPWV). There was a positive correlation between baPWV and radial artery AccV bilaterally. Conclusion Radial artery AccV correlated well with baPWV, which suggests that ultrasound could be used to assess both morphological and functional changes in vessels, may serving as a better method to identify PAS in high-risk COPD patients.

Background Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD. Methods Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603. Results HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-β1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-β1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-β1 induced cell migration. Conclusions These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-β1/Smad2/3 signalling pathway.

Long non-coding RNA（LncRNA）are widely involved in gene expression regulation,epigenetic regulation,transcription and post-transcriptional control. LncRNA SOX2 overlapping transcripts（SOX2OT）can regulate the processes of oxidative stress,cell proliferation and apoptosis,autophagy,inflammation and fibrosis,which will affect the occurrence and development of diabetic kidney disease,diabetic retinopathy,diabetic neuropathy and myocardial metabolic disorders. This article reviews the research progress of LncRNA SOX2OT and DM chronic complications.

DM是一种以慢性高血糖为特征的代谢性疾病,可引起多种慢性并发症.N6-甲基腺苷(m6A)是mRNA中最丰富和可逆的修饰,可简要概括为书写、清除、识别 3 个步骤,在生物发育、代谢和繁殖中发挥重要作用.本文综述m6A甲基化修饰与DM及其慢性并发症相关性的研究进展.

Non-coding RNAs that can not encoding RNA protein,mainly include microRNAs and long non-coding RNAs,in bacteria,fungi,mammals,and many other biological activities life play a very wide range of regulatory role.More and more clinical researchers have begun to pay attention to the biological function of the non-coding RNAs and the relationship between the various diseases of the body,and people gradually realized that the study of non-coding RNAs has important significance for understanding human disease control and biological evolution.

Acute lung injury (ALI) is an acute and progressive pulmonary inflammatory disease that is difficult to cure and has a poor prognosis. Macrophages, which have various phenotypes and diverse functions, play an essential role in the pathogenesis of ALI. Grape seed proanthocyanidin (GSP) has received much attention over several decades, and many biological activities such as anti-apoptotic, antioxidant, and anti-inflammatory have been identified. This study aimed to determine the effect of GSP on lipopolysaccharide (LPS)-induced ALI. In this study, we established an ALI mouse model by tracheal instillation of LPS, and by pre-injection of GSP into mice to examine the effect of GSP on the ALI mouse model. Using H&E staining, flow cytometry, and ELISA, we found that GSP attenuated LPS-induced lung pathological changes and decreased inflammatory cytokine expression in ALI mice. In addition, GSP reduced the recruitment of monocyte-derived macrophages to the lung and significantly promoted the polarization of primary mouse lung macrophages from M1 to M2a induced by LPS. In vitro, GSP also decreased the expression levels of inflammatory cytokines such as TNF-α, IL-6, IL-1β, and M1 macrophage marker iNOS induced by LPS in MH-S cells, while increasing the expression levels of M2a macrophage marker CD206. Bioinformatics analysis identified TREM2 and the PI3K/Akt pathway as candidate targets and signaling pathways that regulate M1/M2a macrophage polarization in ALI, respectively. Furthermore, GSP activated PI3K/Akt and increased TREM2 expression in vivo and in vitro. Meanwhile, GSP's impact on M2a polarization and inflammation suppression was attenuated by the PI3K inhibitor LY294002 or siRNA knockdown TREM2. In addition, GSP-enhanced PI3K/Akt activity was prevented by TREM2 siRNA. In conclusion, this study demonstrated that GSP could ameliorate LPS-induced ALI by modulating macrophage polarization from M1 to M2a via the TREM2/PI3K/Akt pathway.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex progressive inflammatory disease. Necroptosis is a newly identified type of programmed cell death. However, the role of necroptosis in COPD is unclear. This study aimed to identify necroptosis-related genes in COPD and explore the roles of necroptosis and immune infiltration through bioinformatics. The analysis identified 49 differentially expressed necroptosis-related genes that were primarily engaged in inflammatory immune response pathways. The infiltration of CD8+ T cells and M2 macrophages in COPD lung tissue was relatively reduced, whereas that of M0 macrophages was increased. We identified 10 necroptosis-related hub genes significantly associated with infiltrated immune cells. Furthermore, 7 hub genes, CASP8, IL1B, RIPK1, MLKL, XIAP, TNFRSF1A, and CFLAR, were validated using an external dataset and experimental mice. CFLAR was considered to have the best COPD-diagnosing capability. TF and miRNA interactions with common hub genes were identified. Several related potentially therapeutic molecules for COPD were also identified. The present findings suggest that necroptosis occurs in COPD pathogenesis and is correlated with immune cell infiltration, which indicates that necroptosis may participate in the development of COPD by interacting with the immune response.

Background Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. Methods In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. Findings We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). Interpretation In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. Funding National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100). Copyright (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Léri-Weill dyschondrosteosis (LWD) has typical triad: short middle limbs, short stature, Madelung deformity of wrist, and increased body mass index. Short stature and high body mass index are risk factors for metabolic syndrome, type 2 diabetes, cardiovascular diseases, and autoimmune thyroid diseases. However, metabolic disorders and thyroid diseases in adult LWD patients have not been elucidated. This paper reports two adult patients with LWD presented to the Department of Endocrinology and metabolism. By introducing clinical characteristics, genetic variations, and diagnostic methods, physicians can deepen their understanding of LWD, improve diagnosis, and be aware of the comorbid metabolic diseases and thyroid disorders with a view of early prevention and treatment.

Macrophages play an essential role in maintaining the normal function of the innate and adaptive immune responses during host defence. Macrophages acquire diverse functional phenotypes in response to various microenvironmental stimuli, and are mainly classified into classically activated macrophages (M1) and alternatively activated macrophages (M2). Macrophage polarization participates in the inflammatory, fibrotic, and oncogenic processes of diverse respiratory diseases by changing phenotype and function. In recent decades, with the advent of broad-range profiling methods such as microarrays and next-generation sequencing, the discovery of RNA transcripts that do not encode proteins termed "noncoding RNAs (ncRNAs)" has become more easily accessible. As one major member of the regulatory ncRNA family, long noncoding RNAs (lncRNAs, transcripts >200 nucleotides) participate in multiple pathophysiological processes, including cell proliferation, differentiation, and apoptosis, and vary with different stimulants and cell types. Emerging evidence suggests that lncRNAs account for the regulation of macrophage polarization and subsequent effects on respiratory diseases. In this review, we summarize the current published literature from the PubMed database concerning lncRNAs relevant to macrophage polarization and the underlying molecular mechanisms during the occurrence and development of respiratory diseases. These differentially expressed lncRNAs are expected to be biomarkers and targets for the therapeutic regulation of macrophage polarization during disease development.