Exploring a specialized programmed-cell death patterns to predict the prognosis and sensitivity of immunotherapy in cutaneous melanoma via machine learning.

The mortality and therapeutic failure in cutaneous melanoma (CM) are mainly caused by wide metastasis and chemotherapy resistance. Meanwhile, immunotherapy is considered a crucial therapy strategy for CM patients. However, the efficiency of currently available methods and biomarkers in predicting the response of immunotherapy and prognosis of CM is limited. Programmed cell death (PCD) plays a significant role in the occurrence, development, and therapy of various malignant tumors. In this research, we integrated fourteen types of PCD, multi-omics data from TCGA-SKCM and other cohorts in GEO, and clinical CM patients to develop our analysis. Based on significant PCD patterns, two PCD-related CM clusters with different prognosis, tumor microenvironment (TME), and response to immunotherapy were identified. Subsequently, seven PCD-related features, especially CD28, CYP1B1, JAK3, LAMP3, SFN, STAT4, and TRAF1, were utilized to establish the prognostic signature, namely cell death index (CDI). CDI accurately predicted the response to immunotherapy in both CM and other cancers. A nomogram with potential superior predictive ability was constructed, and potential drugs targeting CM patients with specific CDI have also been identified. Given all the above, a novel CDI gene signature was indicated to predict the prognosis and exploit precision therapeutic strategies of CM patients, providing unique opportunities for clinical intelligence and new management methods for the therapy of CM.

[Evaluating the dietary quality of 454 rural elderly aged 65 years and above in Luzhou City in 2023].

OBJECTIVE: To evaluate the dietary quality of the rural elderly aged 65 years and above. METHODS: In February-March 2023, a convenience sampling method was adopted to select 454 rural elderly aged 65 years and above in a township of Luzhou City. The dietary survey was conducted using a semi-quantitative food frequency questionnaire(FFQ-25), and the questionnaire information was collected by face-to-face interviews. Dietary quality was evaluated using the Dietary Balance Index-16(DBI-16) score. RESULTS: The proportion of older people in the region with moderate and high dietary imbalances was 79.7%. Inadequate and excessive dietary intake coexisted. The average daily intake of cereals and potatoes and livestock and meat foods were 356.7 g and 76.2 g, exceeding the recommended intake. The average daily intake of fruit, milk and fish and shrimp intake was 22.8 g, 36 g and 3.7 g, respectively, which was only 10% of the recommended amount, and the intake was seriously insufficient. In addition, the degree of food diversity is relatively low, with most of the average daily intake of food types ranging from five to eight, and only 4.6% of the elderly having more than eight. A total of seven dietary patterns were found among the rural elderly in the region, including a certain degree of under-consumption pattern, a severe under-consumption pattern, a certain degree of over-consumption pattern, and a pattern of both under-consumption and over-consumption. That was dominated by the pattern of severe underconsumption and the pattern of some degree of underconsumption and higher degree of overconsumption, which accounted for 72.3% of the total. CONCLUSION: The rural elderly aged 65 years and above in Luzhou City have a serious dietary imbalance, with a high proportion of insufficient intake of vegetables, fruits and milk, as well as aquatic products and eggs; and excessive intake of livestock, poultry, meat and cereals and potatoes.

Enhancing the Output Performance of Triboelectric Nanogenerator Through Regulation of its Internal Nano-Architecture.

Triboelectric Nanogenerator (TENG) has proven highly effective in converting mechanical energy into electrical energy. Previous research on manipulating microstructure for performance enhancement primarily focused on the surface of TENGs. In this study, an innovative bottom-up strategic design to control the internal nano-architecture for the enhanced output of TENG is proposed. This multiscale structural design strategy consists of defect chemistry (angstrom-scale), surface modification (nano-scale), and spatial regulation of nanoparticles (meso-scale), which helps explore the optimal utilization of TENG's internal structure. After fine-tuning the nano-architecture, the output voltage is significantly increased. This optimized TENG serves as a robust platform for developing self-powered systems, including self-powered electrochemical chlorination systems for sterilization. Additionally, through the utilization of multiscale simulations (density functional theory, all-atom molecular dynamics, and dissipative particle dynamics), the underlying mechanisms governing how the optimized nanoparticle-polymer interface and spatial arrangement of nanoparticles influence the storage and transfer of charges are comprehensively elucidated. This study not only demonstrates the effectiveness of manipulating internal nano-architecture to enhance TENG performance for practical applications but also provides invaluable insights into structural engineering for TENG advancement.

Comparison of six screening methods for sarcopenia among rural community-dwelling older adults: a diagnostic accuracy study.

OBJECTIVE: The objective of this analysis was to determine the diagnostic efficacy of the Ishii test, SarSA-Mod, SARC-F, SARC-Calf, SARC-F+AC, and SARC-Calf+AC for screening for sarcopenia among rural community-dwelling older adults. METHODS: The AWGS 2019 diagnostic criteria was a diagnostic reference for sarcopenia. There were six screening tools whose accuracy was determined through the use of metrics, including specificity, sensitivity, negative and positive predictive values, and the receiver operating characteristic (ROC) curve. RESULTS: The study included 551 participants (304 women, age 70.9 ± 4.9 years). The prevalence of sarcopenia was 44.5% in men and 39.1% in women. In males, the sensitivity/specificity of the Ishii test, SarSA-Mod, SARC-F, SARC-Calf, SARC-F+AC, and SARC-Calf+AC screening sarcopenia were 87.3%/65.7%, 98.2%/21.9%, 6.4%/98.5%, 28.2%/91.2%, 33.6%/83.9%, and 84.6%/43.8%, and in females, they were 68.1%/82.2, 100%/23.2%, 16.0%/90.3%, 35.3%/84.3%, 58.8%/61.1%, and 89.9%/42.2%, respectively. In males, the area under the curves of the Ishii test, SarSA-Mod, SARC-F, SARC-Calf, SARC-F+AC, and SARC-Calf+AC were 0.846 (95% CI 0.795-0.889), 0.800 (95% CI 0.745-0.848), 0.581 (95% CI 0.516-0.643), 0.706 (95% CI 0.645-0.762), 0.612 (95% CI 0.548-0.673), and 0.707 (95% CI 0.646-0.763), respectively, and in females, they were 0.824 (95% CI 0.776-0.865), 0.845 (95% CI 0.799-0.883), 0.581 (95% CI 0.524-0.637), 0.720 (95% CI 0.666-0.770), 0.632 (95% CI 0.575-0.686), and 0.715 (95% CI 0.661-0.765), respectively. CONCLUSION: Our findings demonstrate that the overall accuracy of the Ishii test was best among the six screening tools for sarcopenia screening in rural community-dwelling older adults.

Development and validation of a nomogram model for mortality prediction in stable chronic obstructive pulmonary disease patients: A prospective observational study in the RealDTC cohort.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. There is no nomogram model available for mortality prediction of stable COPD. We intended to develop and validate a nomogram model to predict mortality risk in stable COPD patients for personalised prognostic assessment. Methods: A prospective observational study was made of COPD outpatients registered in the RealDTC study between December 2016 and December 2019. Patients were randomly assigned to the training cohort and validation cohort in a ratio of 7:3. We used Lasso regression to screen predicted variables. Further, we evaluated the prognostic performance using the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curve. We used the AUC, concordance index, and decision curve analysis to evaluate the net benefits and utility of the nomogram compared with three earlier prediction models. Results: Of 2499 patients, the median follow-up was 38 months. The characteristics of the patients between the training cohort (n = 1743) and the validation cohort (n = 756) were similar. ABEODS nomogram model, combining age, body mass index, educational level, airflow obstruction, dyspnoea, and severe exacerbation in the first year, was constructed to predict mortality in stable COPD patients. In the integrative analysis of training and validation cohorts of the nomogram model, the three-year mortality prediction achieved AUC = 0.84; 95% confidence interval (CI) = 0.81, 0.88 and AUC = 0.80; 95% CI = 0.74, 0.86, respectively. The ABEODS nomogram model preserved excellent calibration in both the training cohort and validation cohort. The time-dependent AUC, concordance index, and net benefit of the nomogram model were higher than those of BODEx, updated ADO, and DOSE, respectively. Conclusions: We developed and validated a prognostic nomogram model that accurately predicts mortality across the COPD severity spectrum. The proposed ABEODS nomogram model performed better than earlier models, including BODEx, updated ADO, and DOSE in Chinese patients with COPD. Registration: ChiCTR-POC-17010431.

Effect of continuous positive airway pressure treatment on Th17/Treg imbalance in patients with obstructive sleep apnea and a preliminary study on its mechanism.

BACKGROUND: Obstructive sleep apnea (OSA) can be considered a chronic inflammatory disease that impacts all bodily systems, including the immune system. This study aims to assess the Th17/Treg pattern in patients with OSA and the effect of continuous positive airway pressure (CPAP) treatment. METHODS: OSA patients and healthy controls were recruited. OSA patients recommended for CPAP treatment were followed up for three months. Flow cytometry was employed to determine the proportion of Th17 and Treg cells. Real-time quantitative polymerase chain reaction (PCR) and western blotting were utilized to detect the mRNA and protein levels of receptor-related orphan receptor γt (RORγt) and forkhead/winged helix transcription factor (Foxp3), respectively, in peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum levels of interleukin-17 (IL-17), IL-6, transforming growth factor-ß1 (TGF-ß1), and hypoxia-induced factor-1α (HIF-1α). RESULTS: A total of 56 OSA patients and 40 healthy controls were recruited. The proportion of Th17 cells, Th17/Treg ratio, mRNA and protein levels of RORγt, and serum IL-17, IL-6, and HIF-1α levels were higher in OSA patients. Conversely, the proportion of Treg cells, mRNA and protein levels of Foxp3, and serum TGF-ß1 levels were decreased in OSA patients. The proportion of Th17 and Treg cells in OSA can be predicted by the apnea hypopnea index (AHI), IL-6, TGF-ß1 and, HIF-1α. 30 moderate-to-severe OSA patients were adherent to three-month CPAP treatment, with improved Th17/Treg imbalance, IL-17, IL-6, TGF-ß1, and HIF-1α levels compared to pre-treatment values. CONCLUSION: There was a Th17/Treg imbalance in OSA patients. The prediction of Th17 and Treg cell proportions in OSA can be facilitated by AHI, as well as serum IL-6, TGF-ß1, and HIF-1α levels. Furthermore, CPAP treatment can potentially improve the Th17/Treg imbalance and reduce proinflammatory cytokines in OSA patients.

Obstructive Sleep Apnea Plasma-Derived Exosomes Mediate Cognitive Impairment Through Hippocampal Neuronal Cell Pyroptosis.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with impaired cognitive function. Exosomes are secreted by most cells and play a role in OSA-associated cognitive impairment (CI). The aim of this study was to investigate whether OSA plasma-derived exosomes cause CI through hippocampal neuronal cell pyroptosis, and to identify exosomal miRNAs in OSA plasma-derived. MATERIALS AND METHODS: Plasma-derived exosomes were isolated from patients with severe OSA and healthy comparisons. Daytime sleepiness and cognitive function were assessed using the Epworth Sleepiness Scale (ESS) and the Beijing version of the Montreal Cognitive Assessment Scale (MoCA). Exosomes were coincubated with mouse hippocampal neurons (HT22) cells to evaluate the effect of exosomes on pyroptosis and inflammation of HT22 cells. Meanwhile, exosomes were injected into C57BL/6 male mice via caudal vein, and then morris water maze was used to evaluate the spatial learning and memory ability of the mice, so as to observe the effects of exosomes on the cognitive function of the mice. Western blot and qRT-PCR were used to detect the expressions of Gasdermin D (GSDMD) and Caspase-1 to evaluate the pyroptosis level. The expression of IL-1ß, IL-6, IL-18 and TNF-α was detected by qRT-PCR to assess the level of inflammation. Correlations of GSDMD and Caspase-1 expression with clinical parameters were evaluated using Spearman's rank correlation analysis. In addition, plasma exosome miRNAs profile was identified, followed by Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Compared to healthy comparisons, body mass index (BMI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and ESS scores were increased in patients with severe OSA, while lowest oxygen saturation during sleep (LSaO2), mean oxygen saturation during sleep (MSaO2) and MoCA scores were decreased. Compared to the PBS group (NC) and the healthy comparison plasma-derived exosomes (NC-EXOS), the levels of GSDMD and Caspase-1 and IL-1ß, IL-6, IL-18 and TNF-α were increased significantly in the severe OSA plasma-derived exosomes (OSA-EXOS) coincubated with HT22 cells. Compared to the NC and NC-EXOS groups, the learning and memory ability of mice injected with OSA-EXOS was decreased, and the expression of GSDMD and Caspase-1 in hippocampus were significantly increased, along with the levels of IL-1ß, IL-6, IL-18 and TNF-α. Spearman correlation analysis found that clinical AHI in HCs and severe OSA patients was positively correlated with GSDMD and Caspase-1 in HT22 cells from NC-EXOS and OSA-EXOS groups, while negatively correlated with clinical MoCA. At the same time, clinical MoCA in HCs and severe OSA patients was negatively correlated with GSDMD and Caspase-1 in HT22 cells from NC-EXOS and OSA-EXOS groups. A unique exosomal miRNAs profile was identified in OSA-EXOS group compared to the NC-EXOS group, in which 28 miRNAs were regulated and several KEGG and GO pathways were identified. CONCLUSIONS: The results of this study show a hypothesis that plasma-derived exosomes from severe OSA patients promote pyroptosis and increased expression of inflammatory factors in vivo and in vitro, and lead to impaired cognitive function in mice, suggesting that OSA-EXOS can mediate CI through pyroptosis of hippocampal neurons. In addition, exosome cargo from OSA-EXOS showed a unique miRNAs profile compared to NC-EXOS, suggesting that plasma exosome associated miRNAs may reflect the differential profile of OSA related diseases, such as CI.

TDP43/HDAC6/Prdx1 signaling pathway participated in the cognitive impairment of obstructive sleep apnea via regulating inflammation and oxidative stress.

Neuroinflammation and oxidative stress induced by intermittent hypoxia (IH) are associated with cognitive dysfunction in patients with obstructive sleep apnea (OSA). Recently, TAR DNA-binding protein 43 (TDP-43), histone deacetylase 6 (HDAC6), and peroxiredoxin 1 (Prdx1) have been reported to be involved in cognitive impairment in many degenerative diseases; however, the underlying mechanisms remain unclear. In the present study, subjects underwent polysomnography to diagnose OSA. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) and peripheral blood samples were collected. HMC3 cells were treated with lipopolysaccharide (LPS) to mimic in vitro neuroinflammation. Western blotting was used to assess protein expression and ELISA to assess inflammation and oxidative stress levels. Participants were divided into three groups: healthy control (n = 20); mild to moderate OSA (n = 20); and severe OSA (n = 20). The MoCA scores in mild-moderate OSA and severe OSA were lower than those in healthy controls. Continuous positive airway pressure therapy was found to be effective for cognitive impairment in subjects with severe OSA (24.70 ± 1.81). Expression of TDP-43 and HDAC6 was increased in subjects with OSA, whereas Prdx1 expression was decreased. Alterations in these proteins were partially reversed after 12 weeks of CPAP treatment. Protein expression of TDP-43 and HDAC6 was negatively correlated with MoCA scores in patients with OSA, while Prdx1 expression exhibited the opposite trend. In LPS-treated HMC3 cells, TDP-43 and HDAC6 were upregulated, whereas Prdx1 expression was reduced. TDP-43 influenced the expression of Prdx1 by regulating HDAC6, and inflammation and oxidative stress varied with the expression of TDP-43. When a specific inhibitor of HDAC6 was used, LPS-induced inflammation and oxidative stress were alleviated by an elevated level of Prdx1. In summary, findings of the present study suggest that TDP-43 influenced Prdx1 by regulating HDAC6 expression and promoting neuroinflammation and oxidative stress. This process may be involved in the cognitive impairment experienced by patients with OSA and may provide potential therapeutic targets.

Residents' cognition and attitude towards obstructive sleep apnea hypopnea syndrome. / ä½é™¢åŒ»å¸ˆå¯¹é˜»å¡žæ€§ç¡çœ å‘¼å¸æš‚åœä½Žé€šæ°”ç»¼åˆå¾çš„è®¤çŸ¥åŠæ€åº¦.

OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) may cause damage to many organs of the body and is a potentially fatal disease, which has a serious impact on health and quality of life for patients. Residents play an important role in the screening of OSAHS. This study aims to evaluate the cognition and attitude level of residents towards OSAHS, and to provide evidence for the intervention and diagnosis of the disease. METHODS: A cross-sectional survey of residents at a teaching hospital was conducted from December 1, 2021 to December 1, 2022. A questionnaire was used to assess residents' knowledge, attitudes, and confidence in dealing with OSAHS patients. RESULTS: Of the 200 residents who responded to the questionnaire, 183(91.5%) completed it. The average score on the knowledge scale of Obstructive Sleep Apnea Knowledge and Attitudes Questionnaire (OSAKA) for all residents in this study was 13.12±2.46. The knowledge score of internal medicine residents was higher than that of non-internal medicine residents (13.46±2.22 vs 12.33±2.83, P<0.05), and the mean knowledge score of residents with respiratory rotation experience was higher than that of residents without respiratory rotation experience (13.46±2.35 vs 12.69±2.56, P<0.05). The average score of the attitude/confidence scale on the OSAKA questionnaire for all residents in this study was 3.64±0.62. Of the 183 residents, 60.7% of residents considered OSAHS to be extremely important as a clinical disorder, 72.7% of residents were confident in the identification of OSAHS patients, but only 50.3% were confident in the management of OSAHS patients, and only 42.6% were confident in the management of patients treated with continuous positive pressure ventilation. There was a weak positive correlation among levels of knowledge, attitude, and confidence. CONCLUSIONS: Most residents are aware of the clinical importance of OSAHS, but their knowledge and confidence for OSAHS diagnosis and management are still insufficient, and they need to be trained to manage OSAHS patients.

Prediction of Hospitalization and Mortality in Patients with Chronic Obstructive Pulmonary Disease with the New Global Initiative for Chronic Obstructive Lung Disease 2023 Group Classification: A Prospective Cohort and a Retrospective Analysis.

Background: The revised Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 group ABE classification has undergone major modifications, which can simplify clinical assessment and optimize treatment recommendations for Chronic Obstructive Pulmonary Disease (COPD). However, the predictive value of the new grouping classification for prognosis is worth further exploration. We aimed to compare the prediction of hospitalization and mortality between this new GOLD group 2023 ABE classification and the earlier 2017 ABCD classification in a Chinese COPD cohort. Methods: Data from 2,499 outpatients with COPD, who first registered in the RealDTC study of Second Xiangya Hospital from December 2016 to December 2019, were collected prospectively and assessed retrospectively. Patients were followed up on all-cause mortality until October 2022 or death. Results: Of the 2,499 patients with COPD, the risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The mortality was higher in group E than in groups A and B, and group B was higher than group A. No differences were seen in the area under the curve (AUC) of 2017 vs 2023 GOLD grouping to predict hospitalization. The time-dependent AUC and concordance index for predicting mortality is slightly higher in the GOLD 2017 ABCD than in the 2023 ABE groups. The new GOLD 12-subgroup (1A-4E) classification combining the GOLD 1-4 staging and grouping performed similarly discriminate predictive power for mortality to the GOLD 2017 16-subgroup (A1-4D) classification. Conclusion: The risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The all-cause mortality increased gradually from GOLD group A to E. The GOLD 2023 classification based on ABE groups did not predict mortality better than the earlier 2017 ABCD classifications.

The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

Factors and Molecular Mechanisms of Vitamin A and Childhood Obesity Relationship: A Review.

Childhood obesity has become a public health concern. As the importance of vitamin A (VA) in the body has become increasingly acknowledged, there is limited clinical trial evidence to substantiate the association between VA and childhood obesity. Vitamin A deficiency (VAD) increases the risk of childhood obesity, a finding consistently reported in pregnant women. VA could regulate the adipogenic process, inflammation, oxidative stress and metabolism-related gene expression in mature adipocytes. VAD disrupts the balance of obesity-related metabolism, thus affecting lipid metabolism and insulin regulation. Conversely, VA supplementation has a major impact on efficacy in obesity, and obese individuals typically have a lower VA status than normal-weight individuals. Several studies have attempted to identify the genetic and molecular mechanisms underlying the association between VA and obesity. In this review, we summarize and discuss recent new developments focusing on retinol, retinoic acid, and RBP4 and elucidate and provide an overview of the complex interrelationships between these critical components of VA and childhood obesity. However, the causal relationship between VA status and childhood obesity remains unclear. It is also unknown whether VA supplementation improves the overall obesogenic metabolic profile.

Relationship of Serum 25-Hydroxyvitamin D Levels with Sarcopenia and Body Composition in Community-Dwelling Older Adults: A Paired Case-Control Study.

OBJECTIVES: Sarcopenia is a leading health problem among older adults. However, few studies have explored the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, sarcopenia, and body composition in older Chinese individuals. The aim of this study was to investigate the relationship of serum 25(OH)D levels with sarcopenia, sarcopenia indices, and body composition in community-dwelling older Chinese adults. DESIGN: Paired case-control study. SETTING AND PARTICIPANTS: This case-control study enrolled 66 older adults newly diagnosed with sarcopenia (sarcopenia group) and 66 older adults without sarcopenia (non-sarcopenia group) after screening in the community. METHODS: The definition of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 criteria. Serum levels of 25(OH)D were measured using an enzyme-linked immunosorbent assay. Conditional logistic regression analysis was performed to estimate odds ratios (ORs) and 95% CIs. Spearman's correlation was used to examine the correlations among sarcopenia indices, body composition, and serum 25(OH)D. RESULTS: Serum 25(OH)D levels were significantly lower in the sarcopenia group (29.08 ± 15.11 ng/mL) than in the non-sarcopenia group (36.28 ± 14.68 ng/mL) (P < .05). Vitamin D deficiency was associated with an increased risk of sarcopenia (OR, 7.75; 95% CI, 1.96-30.71). Serum 25(OH)D levels in men were positively correlated with skeletal muscle mass index (SMI) (r = 0.286; P = .029) and negatively correlated with gait speed (r = -0.282; P = .032). Serum 25(OH)D levels in women were positively correlated with SMI (r = 0.450; P < .001), skeletal muscle mass (r = 0.395; P < .001), and fat-free mass (r = 0.412; P < .001). CONCLUSIONS AND IMPLICATIONS: Serum 25(OH)D levels were lower in older adults with sarcopenia than those in adults without sarcopenia. Vitamin D deficiency was associated with increased risk of sarcopenia, and serum 25(OH)D levels were positively correlated with SMI.

The clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease with low body mass index.

Background: This study aimed to analyze the clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease (COPD) with low body mass index (BMI). Methods: In this cross-sectional study, we enrolled patients with stable COPD from the database setup by the Second Xiangya Hospital of Central South University. We classified the patients into three groups based on BMI: low-BMI (<18.5 kg/m2), normal-BMI (≥18.5 and <24.0 kg/m2), and high-BMI (≥24 kg/m2) groups. We defined clinically important deterioration (CID) as a COPD Assessment Test (CAT) score increase of ≥2 and minimum clinically important difference (MCID) as a CAT score decrease of ≥2 during 6 months of follow-up. We recorded the number of exacerbations and mortality during 1 year of follow-up. Results: A total of 910 COPD patients were included with 144 (15.8%) patients in low-BMI, 475 (52.2%) in normal-BMI, and 291 (32.0%) in high-BMI groups. Patients with low BMI had worse pulmonary function, higher symptom scores, and exacerbations in the past year compared with normal- and high-BMI groups (p < 0.05). Logistic regression analysis revealed that age, Global Initiative for Chronic Obstructive Lung Disease grades 3 and 4, and hospitalizations in the past year were independent risk factors for patients with low BMI (p < 0.05). After 1 year of follow-up, patients with low BMI had higher mortality and number of hospitalizations. Patients with low BMI were more likely to attain CID and less likely to attain MCID compared with patients with high BMI (p < 0.05). In addition, patients with low BMI treated with long-acting ß2-agonist (LABA)+long-acting muscarinic antagonist (LAMA) and LABA+LAMA+inhaled corticosteroid (ICS) were more likely to attain MCID than those treated with LABA+ICS and LAMA (p < 0.05). Conclusion: COPD patients with low BMI had worse pulmonary function, higher symptom scores, and higher risk of future hospitalizations and mortality and were less likely to attain MCID and more likely to attain CID. It is worth noting that patients with low BMI treated with LABA+LAMA and LABA+LAMA+ICS were more likely to attain MCID than those treated with LABA+ICS and LAMA.

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. PATIENTS AND METHODS: This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. RESULTS: We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. CONCLUSION: Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

The impact of impaired sleep quality on symptom change and future exacerbation of chronic obstructive pulmonary disease.

PURPOSE: Study the impact of impaired sleep quality on symptom change and future exacerbation of chronic obstructive pulmonary disease (COPD) patients. METHODS: This was a prospective study. Patients with COPD were recruited into the study and followed up for one year. Pittsburgh sleep quality index (PSQI) was collected at baseline. Symptom change was assessed with Minimum clinically important difference (MCID) in COPD Assessment Test (CAT) at 6-month visit, which is an indicator to assess symptom improvement. Exacerbation was recorded during the one-year visit. PSQI score > 5 was defined as poor sleep quality, whereas PSQI score ≤ 5 was defined as good sleep quality. MCID was defined as attaining a CAT decrease ≥ 2. RESULTS: A total of 461 patients were enrolled for final analysis. Two hundred twenty-eight (49.4%) patients had poor sleep quality. Overall, 224 (48.6%) patients attained MCID at 6-month visit and the incidence of exacerbation during the one-year visit was 39.3%. Fewer patients with impaired sleep quality achieved MCID than patients with good sleep quality. Good sleepers were significantly more likely to attain MCID (OR: 3.112, p < 0.001) than poor sleepers. Fewer poor sleepers in GOLD A and D groups attained MCID with ICS/LABA, and fewer poor sleepers in the GOLD D group attained MCID with ICS/LABA/LAMA than good sleepers. Poor sleep quality was a greater risk factor of future exacerbation in Cox regression analysis. The ROC curves showed that PSQI score had a predictive capacity for future exacerbation. More patients with poor sleep quality experienced future exacerbation in GOLD B and D group with treatment of ICS/LABA/LAMA compared to good sleepers. CONCLUSIONS: COPD patients with impaired sleep quality were less likely to achieve symptom improvement and were at increased risk of future exacerbation compared to patients with good sleep quality. Besides, sleep disturbance may affect the symptom improvement and future exacerbation of patients with different inhaled medication or in different GOLD groups.

The clinical characteristics and outcomes of different inhaled therapies in chronic obstructive pulmonary disease patients with frequent cough.

BACKGROUND: Cough is a common symptom in patients with chronic obstructive pulmonary disease (COPD). Patients with cough may exhibit various clinical characteristics and experience varying outcomes based on inhaled therapies they receive. OBJECTIVES: This study aimed to explore the clinical characteristics and outcomes of various inhaled therapies in COPD patients with frequent cough. METHODS: This was a multicenter, prospective cohort study. Of these patients, the median cough score in COPD assessment test (CAT) was two. Patients were classified into frequent cough group if they scored two or over in the first item of CAT and infrequent cough group otherwise. Patients with frequent cough were then divided into long-acting antimuscarinic (LAMA), long-acting beta2-agonist (LABA)/LAMA, inhaled corticosteroids (ICS)/LABA and ICS/LABA/LAMA groups. Minimum clinically important difference (MCID) (CAT scores decreased ≥2 from baseline) and the improvement of cough (cough score decreased ≥1 from baseline) were collected in the six-month follow-up. Frequent exacerbations (experiencing at least two exacerbations) were collected in the one-year follow-up. RESULTS: Of 906 patients, 581 (64.1%) patients reported frequent cough at the initial visit. Frequent cough was associated with the current smokers and CAT scores (p < 0.05). The MCID showed no significant difference between frequent cough and infrequent cough groups in the follow-up. More patients with frequent cough experienced future frequent exacerbations compared to those with infrequent cough. After receiving inhaled therapies, 62% of patients with frequent cough got the cough improved. More patients with frequent cough treated with LABA/LAMA or ICS/LABA/LAMA attained MCID and fewer experienced exacerbations than those treated with LAMA or ICS/LABA (p < 0.05). The change in cough score showed no difference among various inhaled therapies in patients with frequent cough. CONCLUSION: COPD patients with frequent cough were related to current smokers and higher CAT scores. These patients had a higher incidence of frequent exacerbations than those with infrequent cough. Patients with frequent cough who were treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID and at a lower risk of exacerbation than those treated with LAMA or ICS/LABA.

Prohibitin Protects Pulmonary Microvascular Endothelial Cells Against Cigarette Smoke Extract-Induced Cell Apoptosis and Inflammation.

Background: Prohibitin has been identified to play roles in cell survival and apoptosis. Here, this study aimed to clarify the role of prohibitin in cigarette smoke extract (CSE)-induced endothelial cell apoptosis. Methods: The protein level of prohibitin was assessed by Western blot in lung tissues from emphysema and control mice. CSE-induced human pulmonary microvascular endothelial cells (hPMECs) were applied to mimic smoke-related cell apoptosis in vitro. Prohibitin was overexpressed in hPMECs with or without CSE. Mitochondrial function was analyzed by JC-1 staining and ATP assay kits. Oxidative stress was assessed by flow cytometry, fluorescence staining and immunocytochemistry. Apoptosis was analyzed by flow cytometry, Western blot and caspase-3 activity assays. In addition, the expression of inflammatory markers was assessed by Western blot and real-time polymerase chain reaction (PCR). The secretion of inflammatory cytokines was measured by ELISA. Results: Prohibitin was downregulated in emphysema mouse tissues compared with control experiments. Consistently, CSE inhibited both the protein and RNA levels of prohibitin in hPMECs in a dose-dependent manner. Gain-of-function experiments indicated that CSE induced collapse of mitochondrial membrane potential (MMP) and loss of ATP, while prohibitin improved mitochondrial function. CSE induced robust ROS production and oxidative DNA damage, while prohibitin decreased this damage. Upregulation of prohibitin protected the apoptosis of hPMECs from CSE. Overexpression of prohibitin significantly reduced the levels of the main proinflammatory cytokines. Finally, prohibitin inhibited nuclear factor-kappa B (NF-κB) p65 accumulation and IκBα degradation induced by CSE. Conclusion: The current findings suggest that CSE-mediated mitochondrial dysfunction, oxidative stress, cell apoptosis and inflammation in hPMECs were reduced by overexpression of prohibitin. We identified prohibitin as a novel regulator of endothelial cell apoptosis and survival in the context of CSE exposure.

Symptoms at disease onset predict prognosis in COVID-19 disease.

The main clinical manifestations of coronavirus disease 2019 (COVID-19) onset are respiratory symptoms, including cough, sputum, and dyspnea. However, a significant proportion of patients initially manifested non-respiratory symptoms, such as fever, myalgia, and diarrhea. Here, we compared the different characteristics and outcomes between the patients with respiratory symptoms and non-respiratory symptoms at illness onset. The patients admitted to the respiratory departments from eight hospitals in Hunan and Guangxi Province with nucleic acid-positive severe acute respiratory syndrome coronavirus (SARS-CoV-2) were recruited. Epidemiological information, clinical manifestations, laboratory findings, and radiological characteristics, treatment regimens, and outcomes data were recorded and analyzed. The median age of the recruited 541 subjects was 43 years (IQR, 33-55). Of the 541 subjects, 404 (74.5%) subjects had initial symptom that were respiratory, while 137 (25.5%) subjects had non-respiratory symptoms. Respiratory COVID-19 subjects had more secondary bacterial infections (8.7% vs 0.0%, P < 0.001), needed the intensive care unit more (9.7% vs 2.2%, P = 0.005), non-invasive ventilation more (7.2% vs 1.5%, P = 0.004), developed ARDS more (11.4% vs 2.2%, P = 0.001) and needed longer time to recover (18.5 vs 16.7 days, P = 0.003) compared to predominately non-respiratory COVID-19 subjects. The multivariate model showed that age (OR = 1.04, P = 0.01), dyspnea (OR = 4.91, P < 0.001) and secondary bacterial infection (OR = 19.8, P < 0.001) were independently associated with development of ARDS among COVID-19 patients. We identify COVID-19 subjects with dyspnea at disease onset who have a worse prognosis. We also demonstrate age and secondary bacterial infections to be independently associated with ARDS development in subjects with COVID-19.ABBREVIATIONS: COVID-19: Coronavirus disease 2019; ARDS: acute respiratory distress syndrome; IQR: interquartile range; ICU: intensive care unit; CDC: Chinese Center for Disease Control and Prevention.

Comparative clinical characteristics among different age group of adult COVID-19 patients: A multicenter study.

BACKGROUND: Coronavirus disease (COVID-19) is a global infectious disease with a large burden of illness and high health care costs. This study aimed to compare clinical features among adult COVID-19 patients in different age groups. METHODS: Laboratory-confirmed adult COVID-19 infection cases between December 31, 2019 to March 8, 2020 obtained from Neighboring Cities. Patients were divided into five age groups. Clinical characteristics were compared among different age groups. RESULTS: Of 299 cases, median age was 44 and 158 (53%) were male. A total of 53.3% of 30-40 years, 50% of 40-50 years, 36.6% of <30 years and 36.2% of 50-60 years were primary case, none of the elderly were primary case. Among all the observed symptoms, only symptom of dyspnea was significantly different between the elderly group and other groups (p < .001). Proportion of severe or critical type was 2.4%, 5.3%, 9.5%, 14.5%, and 35% in patients with age <30, 30-40, 40-50, 50-65, ≥65, respectively. A total of 285 patients (95.3%) were cured and discharged, 12 patients (4.0%) were still on medical treatment in hospital. There were 2 (0.7%) deaths which occurred among persons ≥65 years. Patients with a history of chronic heart disease had a more than a 56 times higher risk for severe or critical type of COVID-19 than those without a history of chronic heart disease (odds ratio [OR]: 56.038, 95% confidence interval [CI]: 2.764-1136.053, p = .009). Old age (OR: 1.055, 95% CI: 1.016-1.095, p = .006), high heart rate in admission (OR: 1.085, 95% CI: 1.03-1.144, p = .002), high respiratory rate in admission (OR: 1.635, 95% CI: 1.093-2.431, p = .017) were independently associated with severe or critical type in COVID-19. CONCLUSIONS: Proportion of severe or critical type increased with old age groups. Adults with old age and high heart rate, respiratory rate in admission and history of chronic heart disease were associated with severe or critical type in COVID-19.