AOPPs induces EMT and fibrosis by activating oxidative stress through ERK/p38 MAPK signaling pathway in endometriosis.

Epithelial-mesenchymal transition (EMT) is known to play a crucial role in the development of endometriosis (EMs). However, the exact mechanisms involved in EMT regulation in EMs are not well understood. In this study, we performed comprehensive research using clinical samples, single-cell sequencing, and in vivo/in vitro models to investigate the effects of advanced oxidation protein products (AOPPs) on EMT and the underlying mechanisms in EMs. Combining bioinformatics analysis with experimental validation, our results show that AOPPs accumulate in EMs tissues, and their levels positively correlate with the expression of EMT markers in fibrotic lesions of EMs patients. Stimulation with AOPPs leads to a concentration- and time-dependent alteration of EMT markers expression in both in vitro and in vivo models. These effects are mainly mediated by the generation of reactive oxygen species and nitrite, along with the activation of the ERK and P38 signaling pathways. In chronic administration studies using normal rats, AOPPs induce EMT and enhance collagen deposition. These findings significantly contribute to our understanding of the molecular mechanisms of EMs and provide a foundation for future research and therapeutic development in this field.

Impact of acute stress disorder on surfactant protein D levels in acute lung injury.

Many people sustain acute lung injuries in road traffic collisions, but few studies have dealt with such injuries in live models. This study aimed to explore the basic pathophysiological and inflammatory changes in adult rabbits following acute thoracic trauma. We randomly assigned 50 rabbits to control and injury groups. Rabbits in the injury group were subjected to right chest pressure (2600 g) using a Hopkinson bar. Measurements were taken in the control group and 0, 24, 48, and 72 h after injury in the injury group. Injury severity was evaluated in gross view; with haematoxylin and eosin (H&E) staining; and through the serum changes of tumor necrosis factor alpha (TNF-α), surfactant protein D (SP-D), and neutrophils. Secretion changes in SP-D in right lung injured tissues were estimated by western blotting and qPCR. Serum TNF-α levels increased rapidly immediately after injury, gradually recovering after 24, 48, and 72 h (p < 0.01). The percentage of neutrophils in the accompanying blood showed a consistent trend. Gross necropsy and H&E staining indicated different levels of bleeding, alveoli exudation, and inflammatory transformation after impact. ELISA depicted the same trend in circulation (F = 22.902, p < 0.01). Western blotting showed that SP-D protein levels in tissues decreased at 0 h and increased at 24, 48, and 72 h. We demonstrate the feasibility of a model of impact lung injury. Primary impact caused injury without external signs. Inflammation began immediately, and the lungs began recovering at 24, 48, and 72 h, as shown by increased SP-D levels in circulation and tissues.With complaints of ALI and inflammation, SP-D may be a potential biomarker after chest trauma.

The genetic link between thyroid dysfunction and alopecia areata: a bidirectional two-sample Mendelian randomization study.

Background: Although descriptive studies have found an association between thyroid dysfunction (TD) and alopecia areata (AA), however, the causal relationship between TD and AA remains unclear. The purpose of this study is to investigate the causal relationship between the two and the specific directions. Methods: We performed large-scale, two-sample Mendelian randomization (MR) analyses to examine whether there was an association between TD (such as Graves' disease (GD), Hashimoto's thyroiditis (HT), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), etc.) and AA. Genome-wide association study (GWAS) summary statistics for TD and AA were from the IEU OpenGwas project. The inverse variance-weighted (IVW) method was used as the primary analysis method to evaluate the causality between TD and AA, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. In addition, sensitivity analyses were performed to assess the reliability of the study results. Results: Our study found that single nucleotide polymorphisms (SNPs) in HT (IVW OR = 1.396, 95% CI 1.030-1.892, P=0.031) and hypothyroidism (IVW OR = 1.431, 95% CI 1.138-1.799, P=0.002) significantly increased the risk of AA. Reverse MR analysis indicated that genetic susceptibility to AA (ß=-0.029, 95%CI=-0.051 to -0.007, P=0.009) may be a risk for TRH. Positive MR analysis observed no statistically significant causal relationship between other TD and AA (IVW P>0.05). Reverse MR analysis also showed no statistically significant association between AA and other TD (IVW P>0.05) other than TRH. Furthermore, additional sensitivity analyses were performed, including a leave-one-out test, a heterogeneity test, and a pleiotropy test to assess the robustness of the results. Conclusions: This study provides a very comprehensive analysis of the causal relationship between TD and AA, providing convincing genetic evidence to support the causal relationship between TD and alopecia areata. It reveals some causes of AA patients, which is of great significance for the management and treatment of AA patients.

Causal relationships between lung cancer and sepsis: a genetic correlation and multivariate mendelian randomization analysis.

Background: Former research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear. Method: This study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness. Results: LDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, p = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083-1.269, p = 8.29 × 10-5, P fdr = 2.49 × 10-4), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021-1.181, p = 0.012, P fdr = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024-1.178, p = 0.009, P fdr = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047-1.277, p = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship (p > 0.05 and P fdr > 0.05). Conclusion: The study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients.

Shared decision-making in the management of pulmonary nodules: a systematic review of quantitative and qualitative studies.

OBJECTIVE: The objective of this systematic review was to explore the evidence regarding shared decision-making (SDM) in the management of pulmonary nodules. DESIGN: Systematic review of quantitative and qualitative studies. DATA SOURCE: Studies published in English or Chinese up to April 2022 were extracted from nine databases: PubMed, PsycINFO, EMBASE, Cochrane Library, Web of Science and CINAHL, China National Knowledge Infrastructure, Wanfang Data and SinoMed Data. ELIGIBILITY CRITERIA: Studies were eligible if patients or healthcare providers are faced with pulmonary nodule management options or the interventions or experiences were focused on the patient-healthcare provider relationship or health education to make, increase or support shared decisions. All types of studies were included, including quantitative and qualitative studies. Grey literature and literature that had not been peer reviewed were excluded. Poster abstracts and non-empirical publications such as editorials, letters, opinion papers and review articles were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened abstracts and full texts, assessed quality using Joanna Briggs Institute's critical appraisal tools, and extracted data from included studies. Thematic syntheses were used to identify prominent themes emerging from the data. RESULTS: A total of 12 studies met the inclusion criteria, 11 of which were conducted in USA. These included six qualitative studies and six quantitative studies (including both survey and quasi-experimental designs). Three major themes with specific subthemes emerged: (1) Opportunity (uncertainty in the diagnosis and treatment of pulmonary nodules, willingness to participate in decision-making); (2) Ability (patient's lack of knowledge, physician's experience); and (3) Different worldview (misconception, distress among patients, preference for diagnosis and treatment). CONCLUSIONS: Uncertainty in the management of pulmonary nodules is the opportunity to implement SDM. Patients' lack of knowledge, distress, and misunderstandings between healthcare providers and patients are both the main obstacles and the causes of the application of SDM.

Role of Decreased Expression of miR-155 and miR-146a in Peripheral Blood of Type 2 Diabetes Mellitus Patients with Diabetic Peripheral Neuropathy.

Objective: To Study the Correlations of microRNA-155 (miR-155) and microRNA-146a (miR-146a) Expression in Peripheral Blood of Type 2 Diabetes Mellitus (T2DM) Patients with Diabetic Peripheral Neuropathy (DPN), and Explore the Clinical Value of miR-155 and miR-146a in the Diagnosis and Treatment Outcomes of DPN. Methods: The study included 51 T2DM patients without DPN (T2DM group), 49 T2DM patients with DPN (DPN group), and 50 normal controls (NC group). Quantitative real-time PCR was utilized to determine the expression levels of miR-155 and miR-146a. Clinical features and risk factors for DPN were assessed. Multivariate stepwise logistic regression analysis was conducted to confirm whether the expressions of miR-155 and miR-146a could independently predict the risk of DPN. ROC curve analysis evaluated their diagnostic value. Results: The T2DM group exhibited significantly lower expression levels of miR-155 and miR-146a compared to the NC group (P < 0.05). Moreover, the DPN group exhibited a significantly decreased expression level of miR-155 and miR-146a compared to the T2DM group (P < 0.01). Multivariate logistic regression analysis indicated that higher levels of miR-155 and miR-146a might serve as protective factors against DPN development. ROC curve analysis revealed that miR-155 (sensitivity 91.8%, specificity 37.3%, AUC 0.641,) and miR-146a (sensitivity 57.1%, specificity 84.3%, AUC 0.722) possess a strong ability to discriminate between T2DM and DPN. Their combined use further enhanced the diagnostic potential of DPN (sensitivity 83.7%, specificity 60.8%, AUC 0.775). A multi-index combination can improve DPN diagnostic efficiency. Conclusion: The decreased expression of miR-155 and miR-146a in the peripheral blood of T2DM patients is closely related to the occurrence of DPN, highlighting their potential as valuable biomarkers for diagnosing and prognosticating DPN.

Assessing the association between a sedentary lifestyle and prevalence of primary osteoporosis: a community-based cross-sectional study among Chinese population.

OBJECTIVES: To reveal the association between a sedentary lifestyle and the prevalence of primary osteoporosis (POP). DESIGN: A community-based cross-sectional study was conducted. SETTING: This study was conducted in communities in Hefei city, Anhui province, China. PARTICIPANTS: A total of 1346 residents aged 40 and above underwent POP screening via calcaneus ultrasound bone mineral density (BMD) testing and completed a questionnaire survey. OUTCOME MEASURES: The average daily sitting time was included in the study variable and used to assess sedentary behaviour. The 15 control variables included general information, dietary information and life behaviour information. Logistic regression was used to analyse the association between the POP prevalence and study or control variables in different models. RESULTS: 1346 participants were finally included in the study. According to the 15 control variables, the crude model and 4 models were established. The analysis revealed that the average daily sitting time showed a significant correlation with the prevalence of POP in the crude model (OR=2.02, 95% CI=1.74 to 2.36, p<0.001), Model 1 (OR=2.65, 95% CI=2.21 to 3.17, p<0.001), Model 2 (OR=2.63, 95% CI=2.19 to 3.15, p<0.001), Model 3 (OR=2.62, 95% CI=2.18 to 3.15, p<0.001) and Model 4 (OR=2.58, 95% CI=2.14 to 3.11, p<0.001). Besides, gender, age and body mass index showed a significant correlation with the POP prevalence in all models. CONCLUSIONS: This study suggests a potential association between a sedentary lifestyle and the prevalence of POP within the Chinese population. Modifying sedentary behaviours could contribute to a reduction in POP risk. However, longitudinal cohort studies are necessary to confirm this hypothesis in the future.

MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.

Pathophysiological changes and injury markers for acute lung injury from blunt impact in infant rabbits.

Background: Traffic accidents, particularly blunt impacts, cause serious injuries in children. We aimed to assess inflammatory and injury responses in infant rabbits subjected to acute lung injury resulting from blunt impact, with the goal of identifying potential circulatory injury markers. Methods: Forty 4-week-old infant rabbits were subjected to a right chest impact using a Hopkinson bar with 2,600 g. Computed tomography was employed to assess injury severity. Pathological changes were observed using hematoxylin and eosin staining in the control, 0, 24, and 72 h groups, post-injury. Immunohistochemistry was used to examine surfactant protein A (SP-A) changes in right lung tissues and upper main bronchi. Serum levels of interleukin-6 (IL-6), IL-8, and SP-A were measured using ELISA within 24 h post-injury in the control, 0 h, and 24 h groups. Results: Following blunt injury, significant increases were observed in blood white blood cell count (F = 101.556, P < 0.01) and neutrophil percentage (F = 104.228, P < 0.01), which gradually decreased after 24 and 72 h. The lung wet/dry weight ratio indicated significant edema (F = 79.677, P < 0.01), corroborated by hematoxylin and eosin staining showing edema, exudation, and marked granulocyte infiltration in the control, 0 h, 24 h and 72 h groups. SP-A levels decreased rapidly at 0 h, and recovered between 24 and 72 h in the right lung tissues (F = 6.7, P < 0.05), left lung (F = 15.825, P < 0.05) and upper main bronchi (F = 59.552, P < 0.01). The ELISA results showed increasing trends for the control and 0 h groups, while decreasing trends were observed in 24 h group for IL-6 (F = 58.328, P < 0.01) and IL-8 (F = 41.802, P < 0.01). Conversely, SP-A exhibited a decreasing trend in the control and 0 h groups but increased in the serum of 24 h group (F = 52.629, P < 0.01). Discussion: In cases of direct chest trauma in infant rabbits, particularly mild injuries without rib fractures. SP-A levels correlated with pathological changes across all groups and may serve as biomarkers for pediatric blunt lung impact.

Bioinformatics and experimental approach identify lipocalin 2 as a diagnostic and prognostic indicator for lung adenocarcinoma.

BACKGROUND: lipocalin 2 (LCN2) is a secreted glycoprotein that plays key roles in tumorigenesis and progression. Interestingly, LCN2 appears to have a contradictory function in developing lung adenocarcinoma (LUAD). Thus, we intend to explore the role of LCN2 in LUAD through bioinformatics and experimental validation. METHODS: LCN2 expression of LUAD was investigated in the TCGA, TIMER and HPA databases. The relationship between LCN2 and prognosis was investigated by KM plotter, TCGA and GEO databases. GO, KEGG and protein-protein interactions network analysis were conducted to investigate the potential mechanism of LCN2. The relevance of LCN2 to cancer-immune infiltrates was investigated in the TCGA and TIMER databases. Quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay were performed to identify the expression level of LCN2 in cells and serum samples. The CCK-8, wound healing and transwell assay were used to confirm the effect of LCN2 on cell proliferation, migration and invasion in LUAD. The receiver operating characteristic curve was utilized to assess the diagnostic efficiency of LCN2 further. RESULTS: LCN2 expression was significantly upregulated in LUAD (P < 0.05), and was correlated with the clinical stage, tumor size, lymph node metastasis and distant metastasis (P < 0.05). There was a high correlation between high LCN2 and worse prognosis in LUAD. Functional network analysis suggested that LCN2 was associated with multiple signal pathways in cancers, such as JAK-STAT, TNF, NF-κB, HIF-1 and PI3K-Akt signal pathways. In addition, the knockdown of LCN2 significantly inhibited the ability of cell proliferation, migration and invasion. Immune infiltration analysis indicated that LCN2 is associated with multiple immune cell infiltration. Notably, LCN2 demonstrated high diagnostic efficiency for LUAD (AUC = 0.818, P < 0.05), especially for stage III-IV patients could reach 0.895. CONCLUSIONS: LCN2 as an oncogenic glycoprotein promotes the cancer progression related to immune infiltrates, which might be a potential diagnostic and prognostic marker in LUAD.

Highly diverse sputum microbiota correlates with the disease severity in patients with community-acquired pneumonia: a longitudinal cohort study.

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. CONCLUSION: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Crystal plane orientation-dependent surface atom diffusion in sub-10-nm Au nanocrystals.

Surface atom diffusion is a ubiquitous phenomenon in nanostructured metals with ultrahigh surface-to-volume ratios. However, the fundamental atomic mechanism of surface atom diffusion remains elusive. Here, we report in situ atomic-scale observations of surface pressure-driven atom diffusion in gold nanocrystals at room temperature using high-resolution transmission electron microscopy with a high-speed detection camera. The topmost layer of atoms on (001) plane initially diffuse in a column-by-column manner. As diffusion proceeds, the remaining atomic columns collectively inject into adjacent underlayer, accompanied by nucleation of a surface dislocation. In comparison, atoms on (111) plane directly diffuse to the base without collective injection. Quantitative calculations indicate that these crystal plane orientation-dependent atom diffusion behaviors contribute to the larger diffusion coefficient of (111) plane compared to (001) plane in addition to the effect of diffusion activation energy. Our findings provide valuable insights into atomic mechanisms of diffusion-dominant morphology evolution of nanostructured metals and guide the design of nanostructured materials with enhanced structural stability.

[Application of metal cushion block combined with Jumbo cup in reconstruction of acetabular bone defect in revision of artificial hip joint].

OBJECTIVE: To investigate the application effect and imaging changes of metal cushion block combined with Jumbo cup in the reconstruction of acetabular bone defect after revision of artificial hip joint. METHODS: Retrospective analysis was made on the clinical data of 83 patients who underwent revision acetabular bone defect reconstruction of the artificial hip joint in our hospital from September 2019 to October 2021. They were divided into group A and group B according to different surgical methods. There were 42 patients in group A, including 26 males and 16 females, aged from 44 to 72 years old with an average of (60.57±4.62) years, who underwent revision with metal cushion block and Jumbo cup. There were 41 patients in group B, including 22 males and 19 females, aged from 42 to 71 years old with an average of (58.74±4.25) years, who underwent revision with metal cushion block and bone cement mortar cup. The operation related indexes, Harris hip function score and visual analogue scale (VAS) of pain before operation, 1 month and 12 month after operation were compared between two groups. The results of X-ray imaging examination (hip rotation center height, acetabular abduction angle, femoral eccentricity and imaging standard qualification rate) before and 12 month after operation were evaluated, and the incidence of complications was compared between two groups. RESULTS: There was no significant difference in operation time, intraoperative bleeding volume and postoperative drainage volume between two groups (P>0.05). Both groups were followed up for 12 to 36 months with an average of (25.36±3.59) months. The scores of pain, function, deformity and Harris' total score in the two groups at 1 month after operation were higher than those before operation (P<0.05), and the scores of pain, function, deformity, joint activity and Harris' total score in two groups at 1 year after operation were higher than those before operation and 1 month after operation (P<0.05), and the above scores in group A were higher than those in group B at 1 year after operation (P<0.05). The VAS of two groups decreased successively at 1 month and 1 year after operation (P<0.05), but there was no significant difference in both groups at each time point (P>0.05). The femoral eccentricity increased in both groups at 1 year after operation (P<0.05), and group A was higher than group B (P<0.05). The height of rotation center and acetabular abduction angle decreased in both groups at 1 year after operation (P<0.05), and the height of rotation center in group A was lower than that in group B (P<0.05), but there was no significant difference in acetabular abduction angle between two groups (P>0.05). The imaging qualification rate of group A was higher than that of group B (P<0.05). There was no significant difference in the incidence of adverse reactions between two groups (P>0.05). CONCLUSION: Metal cushion block combined with Jumbo cup in the treatment of acetabular bone defects can provide the hip joint function, and restore the hip joint rotation center, femoral eccentricity and acetabular abduction angle, with obvious clinical effect.

The imbalance of pulmonary Th17/Treg cells in BALB/c suckling mice infected with respiratory syncytial virus-mediated intestinal immune damage and gut microbiota changes.

The immune response induced by respiratory syncytial virus (RSV) infection is closely related to changes in the composition and function of gastrointestinal microorganisms. However, the specific mechanism remains unknown and the pulmonary-intestinal axis deserves further study. In this study, the mRNA levels of ROR-γt and Foxp3 in the lung and intestine increased first and then decreased. IL-17 and IL-22 reached the maximum on the third day after infection in the lung, and on the second day after infection in the small intestine and colon, respectively. RegⅢγ in intestinal tissue reached the maximum on the third day after RSV infection. Moreover, the genus enriched in the RSV group was Aggregatibacter, and Proteus was reduced. RSV infection not only causes Th17/Treg cell imbalance in the lungs of mice but also leads to the release of excessive IL-22 from the lungs through blood circulation which binds to IL-22 receptors on the intestinal surface, inducing RegⅢγ overexpression, impaired intestinal Th17/Treg development, and altered gut microbiota composition. Our research reveals a significant link between the pulmonary and intestinal axis after RSV infection. IMPORTANCE: RSV is the most common pathogen causing acute lower respiratory tract infections in infants and young children, but the complex interactions between the immune system and gut microbiota induced by RSV infection still requires further research. In this study, it was suggested that RSV infection in 7-day-old BALB/c suckling mice caused lung inflammation and disruption of Th17/Treg cells development, and altered the composition of gut microbiota through IL-22 induced overexpression of RegⅢγ, leading to intestinal immune injury and disruption of gut microbiota. This research reveals that IL-22 may be the link between the lung and gut. This study may provide a new insight into the intestinal symptoms caused by RSV and other respiratory viruses and the connection between the lung and gut axis, as well as new therapeutic ideas for the treatment of RSV-infected children.

Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.

AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.

Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.

OBJECTIVE: Non-small-cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). METHODS AND RESULTS: In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid-2-related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. CONCLUSION: This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.

Association between body roundness index and prevalence of kidney stone in the U.S: a study based on the NHANES database.

OBJECTIVE: This study aimed to evaluate the potential association between the body roundness index (BRI) and kidney stone prevalence in adults in the United States. METHODS: A cohort of participants from the National Health and Nutrition Examination Survey (NHANES) database spanning 2007-2018 were gathered for analysis. Logistic regression analyses, subgroup assessments, and calculations were employed to examine the potential link between BRI and kidney stone prevalence. RESULTS: The study included 30,990 participants aged > 20 years, of which 2,891 declared a kidney stone history. After modulating all relevant confounding factors, each unit increase in the BRI was linked to a 65% increase in kidney stone prevalence (OR = 1.65, 95% CI: 1.47, 1.85). Sensitivity analyses conducted by categorizing the BRI into three groups revealed a 59% increase in kidney stone prevalence in the highest tertile BRI group compared to the lowest one (OR = 1.59, 95% CI: 1.42, 1.79). Furthermore, dose-response curves depicted a positive near-linear correlation between the BRI and the risk of kidney stone prevalence. CONCLUSION: These findings suggest a clinically noteworthy positive correlation between higher BRI values and kidney stone prevalence among the studied US adult population. However, it is essential to acknowledge that the observed relationship does not establish a causal link.

Identification and validation of a glycosyltransferase gene signature as a novel prognostic model for lung adenocarcinoma.

Background: The role of glycosyltransferase (GT) genes in lung adenocarcinoma (LUAD) needs further elucidation. Thus, our study aims to identify the prognostic gene signature of LUAD and explore its molecular functions. Methods: We initially extracted GT gene sets from the database, and obtained mRNA expression levels and clinical data from The Cancer Genome Atlas (TCGA) database. For constructing a prognostic model for GT genes, we utilized univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Using the model, patients were categorized into high- and low-risk groups. Additionally, we evaluated differences in tumor immune infiltration between these groups and identified potential therapeutic drugs. Finally, we experimentally validated the expression levels of these crucial prognostic genes. Results: We developed a risk score comprising nine GT genes (C1GALT1, FUT1, GALNT2, PLOD2, POMK, PYGB, ST3GAL6, UGT2B11, UGT3A1). Patients were then categorized into low- and high-risk groups based on this score. The low-risk group showed superior overall survival (OS) compared to the high-risk group. There were significantly distinct tumor immune microenvironment statuses observed between the two groups. We identified potential therapeutic drugs, including the MEK inhibitor (PD-184352). Finally, we verified the expression of these nine GT genes through immunohistochemistry (IHC) staining and quantitative real-time PCR (qPCR). Conclusion: We identified a distinct LUAD GT gene signature, and these differentially expressed mRNAs could serve as valuable prognostic biomarkers and therapeutic targets. Furthermore, we experimentally validated their expression levels and identified potential therapeutic agents.