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Cheng Ma,1,* Qi Chen,2,* Yi-Fan Wei,1,* Shu-Wen Chen,3 Huan Liu,4 Feng Xin,5 Yong-Xin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Clinical College, The First Clinical School of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Orthopaedics, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 5Department of Orthopaedics, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, 221005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Xin; Yong-Xin Ren, Email 925866554@qq.com; renyongxinjsph@163.comBackground: Osteoarthritis (OA) is a leading cause of pain, disability, and reduced mobility worldwide, characterized by metabolic imbalances in chondrocytes, extracellular matrix (ECM), and subchondral bone. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in OA pathogenesis. This study focuses on lncRNA PTS-1, a novel lncRNA, to explore its function and regulatory mechanisms in OA progression.Methods: The expression profile of lncRNAs was assessed using RNA sequencing and qRT-PCR. The expression of lnc-PTS-1 was further validated by qRT-PCR in degenerated cartilage tissues, degenerative primary chondrocytes, and IL-1β-treated C28/I2 cells. Cell viability, proliferation, and apoptosis rates, along with the mRNA and protein levels of apoptosis-related markers (cleaved Caspase 3, cleaved Caspase 9, Bcl-2, Bax), ECM metabolism markers (MMP-3, MMP-13, aggrecan, collagen II), and inflammation-related markers (IL-1β, IL-6, TNF-α) were evaluated using Cell Counting Kit-8, Toluidine Blue staining, Alcian Blue staining, flow cytometry, qRT-PCR, immunofluorescence, and Western Blot. The interaction between miR-8085 and lnc-PTS-1 or E2F2 was investigated through dual luciferase reporter assays and RNA immunoprecipitation (RIP) analyses.Results: Lnc-PTS-1 expression was significantly downregulated in degenerated cartilage tissues, IL-1β-induced degenerative primary chondrocytes and C28/I2 cells. Functional experiments showed that lnc-PTS-1 knockdown aggravated IL-1β-induced ECM degradation, chondrocyte apoptosis, and inflammation, while its overexpression provided protective effects. Mechanistically, lnc-PTS-1 acted as a competing endogenous RNA (ceRNA) by sponging miR-8085, thereby upregulating E2F2 expression. Notably, miR-8085 upregulation diminished the protective effects of lnc-PTS-1 on ECM degradation, apoptosis, and inflammation, while E2F2 upregulation partially alleviated IL-1β-induced damage. However, these mitigating effects were reversed by miR-8085 overexpression.Conclusion: These findings identify lnc-PTS-1/miR-8085/E2F2 axis as a novel regulatory mechanism in OA pathogenesis, providing theoretical basis and experimental evidence for the potential clinical application of new lncRNA molecules in the treatment of OA.Keywords: osteoarthritis, long non-coding RNA PTS-1, E2F2, miR-8085

Yuan-Qin Du,1,* Bin Yuan,1,* Yi-Xian Ye,1 Feng-ling Zhou,1 Hong Liu,1 Jing-Jing Huang,2 Yan-Fei Wei3,4 1Graduate School, Guangxi University of Traditional Chinese Medicine, Nanning, 530200, People’s Republic of China; 2The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530024, People’s Republic of China; 3Department of Physiology, Guangxi University of Traditional Chinese Medicine, Nanning, 530200, People’s Republic of China; 4Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Nanning, 530200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Fei Wei, Department of Physiology, Guangxi University of Traditional Chinese Medicine, No. 13 Wu He Road, Nanning, 530200, People’s Republic of China, Tel/Fax +86-771-4733794, Email weiyanfei@gxtcmu.edu.cnBackground/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) in HCC.Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-β-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot.Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells.Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.Keywords: plumbagin, hepatocellular carcinoma, epithelial-mesenchymal transition, pulmonary metastasis, Snail

Meng-Jer Hsieh,1 Ning-Hung Chen,2 Shih-Lung Cheng,3,4 Chi-Wei Tao,5 Yu-Feng Wei,6,7 Yao-Kuang Wu,8 Ming-Cheng Chan,9,10 Shih-Feng Liu,11– 13 Wu-Huei Hsu,14 Tsung-Ming Yang,15 Ming-Shian Lin,16,17 Ching-Lung Liu,18 Ping-Hung Kuo,19 Ying-Huang Tsai1,20 1Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital and School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 4Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli, Taoyuan, Taiwan; 5Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 6School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 9Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 10National Chung Hsing University, Taichung, Taiwan; 11Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 13College of Medicine, Chang Gung University, Taoyuan, Taiwan; 14Critical Medical Center, China Medical University Hospital, Taichung, Taiwan; 15Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 16Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; 17Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 18Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 19Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 20Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of ChinaCorrespondence: Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, No. 5 Fu-Xin St, Kweishan District, Taoyuan, Taiwan, Email chestmed@cgmh.org.twBackground: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan.Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics.Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period.Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.Keywords: tiotropium/olodaterol, umeclidinium/vilanterol, indacaterol/glycopyrronium, LABA/LAMA therapy, Taiwan, cohort study, propensity score matching, chronic obstructive pulmonary disease, moderate-to-severe exacerbation

Kuang-Ming Liao,1 Chao-Ming Hung,2 Chin-Chung Shu,3,4 Ho-Sheng Lee,5 Yu-Feng Wei6,7 1Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan; 2Department of Surgery, E-Da Cancer Hospital, Kaohsiung, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 4National Taiwan University College of Medicine, Taipei, Taiwan; 5Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; 6School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, TaiwanCorrespondence: Yu-Feng WeiDepartment of Internal Medicine, E-Da Hospital, No. 1, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung, 824, TaiwanTel +886-7-6150011Fax +886-7-6150927Email yufeng528@gmail.comBackground: Limited studies have focused on the impact of the coexistence of small cell lung cancer (SCLC) and chronic obstructive pulmonary disease (COPD). The study was to examine the impact of COPD on mortality in SCLC patients.Methods: We analyzed SCLC patients from the Taiwan Cancer Registry Database between January 1, 1997, and December 31, 2015. The COPD population was composed of patients with a COPD diagnosis before the diagnosis of SCLC. The control group was composed of randomly selected SCLC patients without COPD who were propensity score matched with those with concomitant COPD according to age, sex, index date, cancer staging and comorbidities at a 1:1 ratio.Results: Among 9425 SCLC patients in the database, eligible subjects were divided into the COPD group (n = 4235) and the non-COPD group (n = 2334). Compared to patients in the non-COPD group, the patients in the COPD group were older (71.4 versus 65.7 years, p< 0.0001), had a lower percentage of stage IV disease (60.1% versus 68.3%, p< 0.0001) and had more comorbidities. After matching, there were 1457 patients in each group. Older age, lower body mass index (BMI), and some comorbidities were associated with higher mortality, and comorbid COPD was associated with lower 1-year mortality in SCLC patients. Multivariate analysis identified older age, lower BMI, and concomitant congestive heart failure or diabetes as risk factors for OS.Conclusion: A diagnosis of COPD was associated with reduced 1-year mortality in SCLC patients, but no significant difference after 1-year in this population.Keywords: chronic obstructive pulmonary disease, small cell lung cancer

Cheng-Yu Chang,1,&ast; Chung-Yu Chen,2,3,&ast; Shih-Chieh Chang,4– 6,&ast; Yi-Chun Lai,4,5 Yu-Feng Wei7– 9 1Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; 3College of Medicine, National Taiwan University, Taipei, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 5Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 6Department of Critical Care Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 7School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 8Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 9Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yu-Feng WeiDepartment of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan, No. 21, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung, 824, TaiwanTel +886-7-6150011Fax +886-7-6150927Email yufeng528@gmail.comIntroduction: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated.Methods: We enrolled patients 65 years or older with EGFR-mutated Stage IIIB–IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS).Results: From January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2– 4). Compared with patients categorized as good PS (0– 1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, < 3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS.Conclusion: In older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and < 3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.Keywords: older adults, epidermal growth factor receptor tyrosine kinase inhibitor, non-small-cell lung cancer, performance status

Meng-Jer Hsieh,1,2 Shu-Yi Huang,1 Tsung-Ming Yang,1 Chi-Wei Tao,3 Shih-Lung Cheng,4 Chao-Hsien Lee,5 Ping-Hung Kuo,6 Yao-Kuang Wu,7,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Ming-Shian Lin,12 Chin-Chou Wang,13 Yu-Feng Wei,14 Ying-Huang Tsai1,2 1Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang-Gung Medical foundation, Chiayi, Taiwan; 2Department of Respiratory Therapy, School of Medicine, Chang-Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 8School of Medicine, Tzu Chi University, Hualien, Taiwan; 9Department of pulmonary and critical care medicine, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 11Division of Chest Medicine, Taichung Veterans General Hospital, Taiwan; 12Dpartment of Internal Medicine, Ditmanson Medical Foundation, Chia-Yi Cristian Hospital, Chia-Yi, Taiwan; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang-Gung Medical Foundation, Kaohsiung, Taiwan; 14Department of Internal Medicine E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Background: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methods: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.Results: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.Conclusion: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. Keywords: chronic obstructive pulmonary disease, GOLD guidelines, inhaled corticosteroids, long-acting bronchodilators

Li Cao, Yan Liu, Li Zhang, Yanfei Wei Intensive Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi, China Objective: The primary objective of this study was to evaluate whether the polymorphism of poly (ADP-ribose) polymerase-1 (PARP-1) is involved as a potential risk factor in the development of acute renal injury in elderly Chinese patients with diabetes mellitus. Subjects and methods: In this pilot study, diabetic patients of either gender (aged ≥65 years) with a confirmed diagnosis of acute renal injury and individuals with no clinical symptoms of acute renal injury were enrolled at Nanxishan Hospital of Guangxi Zhuang Autonomous Region, China. Genetic polymorphism of PARP-1 was assessed using polymerase chain reaction-restriction fragment length polymorphism assay. Cytokine levels (interleukin [IL]-6, IL-1β and tumor necrosis factor-alpha) were measured in the serum samples by sandwich enzyme-linked immunosorbent assay technique. Results: A total of 130 Chinese patients with acute renal injury and 130 Chinese individuals with no clinical symptoms of acute renal injury were included. We found that the patients with GG genotype and carriers of the G and C alleles of PARP-1 were at high risk of developing acute renal injury. Moreover, del/ins polymorphism of the NF-κB1 gene was also found to be associated with acute renal injury. In addition, the levels of IL-6, IL-1β and tumor necrosis factor-alpha were significantly increased in patients with acute renal injury (p

Yu-Feng Wei,1,2 Ying-Huang Tsai,3 Chin-Chou Wang,4 Ping-Hung Kuo5 On behalf of the TOLD Study Group 1Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 2Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 4Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China Purpose: A low body mass index (BMI) is a poor prognostic marker of acute exacerbations and mortality in patients with COPD. However, the impact of overweight and obesity on COPD-related outcomes is uncertain. The aim of this study was to examine whether a high BMI is associated with the frequent exacerbator phenotype (≥2/year) in Taiwanese patients with COPD. Patients and methods: Data were obtained from the Taiwan Obstructive Lung Disease study, a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals in Taiwan. Multivariate logistic regression models were used to explore the association between BMI and other factors with the frequency of COPD exacerbations in these patients. Results: Among the whole study cohort (n=1,096), 735 (67.1%) had no exacerbations and 148 (13.5%) were frequent exacerbators in the previous year. The BMI values of the patients with 0, 1, and ≥2 exacerbations were 23.6, 23.5, and 22.6 kg/m2, respectively. In all, 256 (23.4%) and 196 (17.9%) patients were overweight (27 kg/m2 > BMI ≥24 kg/m2) and obese (BMI ≥27 kg/m2), respectively. Even after adjusting for multiple factors, overweight and obesity were associated with the frequency of exacerbations (odds ratio [95% confidence interval] 0.49 [0.28–0.87, P=0.015] and 0.49 [0.26–0.94, P=0.033], respectively). Conclusion: Our results suggest that overweight and obesity are associated with a lower frequency of COPD exacerbations in Taiwan. Keywords: acute exacerbation, COPD, obesity, overweight

Jung-Yueh Chen,1,* Jui-Ming Liu,2,* Fung-Wei Chang,3 Hung Chang,4,5 Kuan-Chen Cheng,6,7 Chia-Lun Yeh,2 Yu-Feng Wei,1 Ren-Jun Hsu8–10 1Division of Chest Medicine, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, 2Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 3Department of Obstetrics & Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 4Division of Thoracic Surgery, Department of Surgery, Taichung Armed Forces General Hospital, Taichung, 5Department of Physiology, National Defense Medical Center, 6Graduate Institute of Food Science and Technology, National Taiwan University, 7Institute of Biotechnology, National Taiwan University, 8Graduate Institute of Life Sciences, National Defense Medical Center, 9Department of Pathology, Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, 10Biobank Management Center, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan *These authors contributed equally to this work Background: Scabies is a common parasitic infectious disease, and COPD is a major pulmonary disease. However, there have been no previous studies that have investigated the relationship between scabies and COPD. Materials and methods: This nationwide population-based study included a total of 3,568 patients with scabies as the study group and 14,255 patients as a control group. We followed up patients in both groups for a 5-year period to identify any new diagnoses of COPD. We then followed them up for an additional 2-year period to determine the severity of any newly diagnosed cases of COPD as indicated by acute respiratory events. Cox proportional hazard regression analyses were performed to calculate the hazard ratio (HR) of COPD during the 5-year follow-up period and COPD complication during the additional 2-year follow-up period. Results: Of the 17,823 patients in the study, 2,765 (15.5%) were newly diagnosed with COPD during the 5-year follow-up period; 904 (32.7%) were from the scabies group; and 1,861 (67.3%) were from the control group. Compared to the patients without scabies, the adjusted HR (aHR) for COPD for the subjects with scabies was 1.72 (95% CI: 1.59–1.87) during the 5-year follow-up period. For those newly diagnosed with COPD, the aHR for COPD with acute exacerbation was 1.85 (95% CI: 1.67–2.06), the aHR for COPD with pneumonia was 3.29 (95% CI: 2.77–3.92), the aHR for COPD with acute respiratory failure was 4.00 (95% CI: 3.08–5.19), and the aHR for COPD with cardiopulmonary arrest was 3.95 (95% CI: 2.25–6.95) during the additional 2-year follow-up period. Conclusion: The results of this study indicate a 72% increased risk for COPD among patients with scabies. The results also reveal an increased risk of severe COPD complications such as acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation among patients with scabies. This useful information may help physicians in treating scabies and remaining alert to the potential development of COPD and its severe complications. Keywords: scabies, chronic obstructive pulmonary disease, National Health Insurance Research Database

Wan-Chun Huang,1 Ying-Huang Tsai,2 Yu-Feng Wei,3 Ping-Hung Kuo,4 Chi-Wei Tao,5 Shih-Lung Cheng,6 Chao-Hsien Lee,7 Yao-Kuang Wu,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Chin-Chou Wang,12 Ming-Shian Lin1,131Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 2Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 3Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, 4Department of Internal Medicine, National Taiwan University Hospital, 5Department of Internal Medicine, Cheng-Hsin General Hospital, 6Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, 7Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, 9Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 11Division of Chest Medicine, Taichung Veterans Genera Hospital, Taichung, 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 13Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan, Republic of ChinaBackground: COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.Methods: The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.Results: Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P

Yu-Feng Wei,1 Ping-Hung Kuo,2 Ying-Huang Tsai,3 Chi-Wei Tao,4 Shih-Lung Cheng,5,13 Chao-Hsien Lee,6 Yao-Kuang Wu,7 Ning-Hung Chen,8 Wu-Huei Hsu,9 Jeng-Yuan Hsu,10 Ming-Shian Lin,11 Chin-Chou Wang12 1Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 5Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan; 8Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University and China Medical University Hospital, Taichung, Taiwan; 10Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 13Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan Background and objective: The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice. The aim of this study was to explore the factors associated with the use of ICS in these patients. Methods: The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan. Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients. Results: Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively). The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients. Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14–4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24–2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40–2.96; P

Guangying Cui,1,2 Jianing Chen,1,2 Jianqin He,1,2 Chong Lu,1,2 Yingfeng Wei,1,2 Lin Wang,1,2 Xuejun Xu,3 Lanjuan Li,1,2 Toshimitsu Uede,4 Hongyan Diao1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 3Department of Oral Orthodontics, Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan Purpose: Dendritic cells (DCs) play critical roles in promoting innate and adaptive immunity in microbial infection. Functional impairment of DCs may mediate the suppression of viral-specific T-cell immune response in chronic hepatitis B (CHB) patients. Osteopontin (OPN) is involved in several liver diseases and infectious diseases. However, whether OPN affects DC function in hepatitis B virus (HBV) infection is unknown.Methods: Twenty CHB patients and 20 healthy volunteers were recruited. OPN secreted by DCs was compared. Peripheral blood mononuclear cells cultured with OPN antibody were examined to study the costimulatory molecular expression and interleukin (IL)-12 production of DCs after HBV antigenic stimulation. OPN-deficient mice were used to investigate the influence of OPN on DC maturation and function after HBV antigenic stimulation in vitro and in vivo. Exogenous OPN was administrated to further verify the functioning of DCs from CHB patients upon HBV antigenic stimulation.Results: We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers. The absence of OPN impaired IL-12 production and costimulatory molecular expression of DCs upon stimulation with HBV antigens. Defective DC function led to reduced activation of Th1 response to HBV antigens. In addition, OPN deficiency in DCs reduced the HBV antigen-induced inflammatory response in the liver of mice. Importantly, OPN administration significantly promoted the maturation of DCs from CHB patients in vitro.Conclusion: These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine. Keywords: osteopontin, dendritic cells, hepatitis B virus

Background: Intervertebral disc degeneration (IVDD) stands as a primary pathophysiological driver of low back pain, yet no therapeutic intervention effectively arrests its progression. Evidence shows that certain Sirt1 agonists may confer protective effects on intervertebral discs, but the underlying mechanisms remain unclear. This study aims to delineate the interaction between Sirt1 and the inflammatory microenvironment, offering potential novel avenues for IVDD prevention and treatment., Methods: In vitro IL-1β-induced nucleus pulposus cells (NPCs) degenerative model and in vivo a mouse annulus fibrosus needle puncture model in Sirt1 transgenic (Sirt1 TG ) and the same litter WT mice were used to investigate the role of Sirt1 in homeostasis and inflammation. Mechanistic insights were obtained through RNA sequencing, co-immunoprecipitation (Co-IP), luciferase assays, and chromatin immunoprecipitation-(ChIP)-PCR. A co-culture system of Raw264.7 and NPCs was employed to assess the involvement of Lipocalin 2., Results: Our study demonstrated reduced Sirt1 expression in degenerating human nucleus pulposus (NP) tissue. Both in vitro and in vivo data revealed that NP-specific overexpression of Sirt1 inhibited extracellular matrix degradation and inflammation. Mechanistically, Sirt1 suppressed the acetylation of RelA/p65 at lysine 310 and phosphorylation at serine 536, with the C-terminus of Sirt1 and the RHD-NLS domain of RelA mediating to their interaction. Furthermore, NPCs-derived Lipocalin 2 was identified as a cytokine involved in macrophage chemotaxis and M1 polarization to exacerbate inflammation., Conclusion: Our work revealed that Sirt1 negatively regulates Lipocalin 2, thereby ameliorating the inflammatory milieu and blocking NPCs and macrophages crosstalk., The Translational Potential of This Article: This study illuminates the crucial role and molecular mechanisms of Sirt1 in regulating the NP microenvironment. These insights shed light on strategies for the prevention and treatment of IVDD-related herniation and low back pain. By pinpointing specific biological targets, the screening of smallmolecule compounds with significant clinical implications can be facilitated. This translational innovation promises to optimize cells communication within intervertebral disc microenvironment via localized drug delivery, potentially improving patient outcomes and satisfaction following spinal fusion or discectomy surgeries., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background/purpose: This multi-institutional study was aimed to analyze prognostic factors of completely resected early stage thymoma., Methods: Patients with surgically treated early stage thymoma between 1988 and 2019 were enrolled. Statistical associations were evaluated using the χ 2 test, Fisher's exact test, and Student's t-test. Disease-free survival (DFS) and overall survival (OS) curves were established by the Kaplan-Meier method, and compared using the log-rank test., Results: A total of 229 patients with Masaoka stage I and 131 with Masaoka stage II thymoma were included. The DFS of patients with Masaoka stage I thymoma was associated with neutrophil-to-lymphocyte ratio (NLR, hazard ratio [HR] = 3.18, 95% confidence interval [CI]: 1.34-7.54), and extrathymic malignancies (HR = 4.51, 95% CI: 2.02-10.11), and the OS was associated with NLR (HR = 5.03, 95% CI: 1.61-15.66) and extrathymic malignancies (HR = 7.68, 95% CI: 3.12-18.97). In patients with Masaoka stage II thymoma, DFS was associated with age (HR = 2.50, 95% CI: 1.18-5.27), extent of surgery (HR = 0.41, 95% CI: 0.19-0.87), and NLR (HR = 3.23, 95% CI: 1.11-9.44), and OS was associated with age (HR = 5.77, 95% CI: 1.81-18.34), surgical approach (HR = 8.40, 95% CI: 1.91-37.00), and extrathymic malignancies (HR = 2.96, 95% CI: 1.08-8.12)., Conclusion: In Masaoka stage I thymoma, preoperative NLR and extrathymic malignancies are independently associated with DFS and OS. In Masaoka stage II thymoma, age, extent of surgery, and NLR are independently associated with DFS, and age, surgical approach, and extrathymic malignancies are associated with OS., Competing Interests: Declaration of competing interest All authors declare that there is nothing to be disclosed in this study., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Ovarian cancer (OC) is a heterogeneous malignancy with multiple histological subtypes, showing global variability in incidence. Temporal changes in diagnostic criteria and risk factors might influence the incidence and distribution of OC and its subtypes., Methods: This study analyzed incidence patterns (2013-2017) and trends (1988-1992 to 2013-2017) of OC and its subtypes across 65 and 40 countries, respectively. Data were extracted from the Cancer Incidence in Five Continents (CI5 Ⅻ) and CI5plus databases (accessed in June 2024). Annual percent changes were computed to describe trends in age-standardized rates (ASRs) of OC and its subtypes. Proportions of ASR for each subtype relative to the ASR of OC for individual countries were calculated., Findings: The incidence of OC displayed marked disparities across regions and Human Development Index (HDI), with the highest ASRs in Eastern and Central Europe and very high HDI regions, and the lowest in Africa, Asia, and medium HDI regions. Despite stable trend in ASRs of OC globally, notable declines were observed in Europe, America, and Oceania, in contrast to increases in Asian countries like Japan and South Korea. Globally, serous carcinomas remained the most prevalent subtype. European countries exhibited a higher proportion of serous carcinomas, while Asian countries had a higher proportion of endometrioid and clear cell carcinomas. Although trends in subtypes also remained stable, ASRs increased over time for serous carcinomas and germ cell tumor in most countries, while mucinous carcinomas and adenocarcinoma NOS showed a decline., Interpretation: Variations in global patterns and trends in OC incidence and its subtypes might be influenced by genetic and reproductive factors. Consequently, region-specific prevention strategies and ongoing surveillance are essential to mitigate the burden of OC., Funding: The National Key Research and Development Program of China (No.2022YFC2704205), the Natural Science Foundation of China (No.82073647, 82373674, and 82103914), Outstanding Scientific Fund of Shengjing Hospital, 345 Talent Project of Shengjing Hospital of China Medical University, the Max Planck - University of Helsinki Center from the Jane and Aatos Erkko Foundation (No.210046), the Max Planck Society (No.5714240218), the University of Helsinki (No.77204227), and the European Union (ERC Synergy, BIOSFER, 101071773)., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Although (poly)phenols have shown potential in anti-cancer activities, their impact on improving ovarian cancer (OC) survival remains unknown. Therefore, we aim to first investigate the association between dietary polyphenol intake and OC survival, providing valuable insights into potential interventions., Methods: The prospective cohort recruited 560 patients with OC to assess the associations of polyphenol intake, not only pre- and post-diagnosis but also the change from pre- to post-diagnosis with OC survival. Dietary intakes of total (poly)phenols and their five classes (flavonoids, phenolic acids, lignans, stilbenes, and other polyphenols) were assessed using a validated 111-item food frequency questionnaire. Overall survival (OS) was tracked through active follow-up and medical records until February 16th, 2023. Cox proportional hazard regression models were applied to calculate the hazard ratios (HR) and 95% confidence intervals (CI)., Results: During a median follow-up of 44.4 months, 211 all-cause deaths were identified. We observed significant associations between higher polyphenol intake with lower risk of mortality among patients with OC ((HR T3 vs. T1 = 0.55, 95%CI = 0.35-0.87 for pre-diagnosis; and HR T3 vs. T1 = 0.59, 95%CI = 0.39-0.90 for post-diagnosis). Consistently, an evident linear trend was observed for polyphenol and flavonoid intake with OC survival. Of note, compared to the stable group (change within 10%), the decreased intake (change of more than 10%) of total (poly)phenols and five polyphenol classes was significantly associated with worse OS., Conclusion: Dietary (poly)phenols, as well as its five classes, have an inverse association with OC survival., Competing Interests: Declarations. Ethics approval and consent to participate: The OOPS was approved by the Institutional Review Board of the Ethics Committee of Shengjing Hospital of China Medical University. All participants signed informed consent. Competing interests: The authors declare that they have no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis., Objective: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC)., Methods: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models., Results: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05-3.79), Cd (OR=2.56, 95 %CI: 1.29-5.05), Hg (OR=2.24, 95 %CI: 1.09-4.62), and Pb (OR=3.80, 95 %CI: 1.75-8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures., Conclusions: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping., Methods: We conducted a prospective trial including 39 patients with newly diagnosed stage IV lung adenocarcinoma who presented with MPE. Tissue tests matching hotspot variants, including EGFR, ALK, and ROS1, were compared with the AlphaLiquid100 of PE-cfDNA., Results: Among the 39 PE-cfDNA samples successfully sequenced, 32 (82.1%) had a PE cell-block tumor content of < 10%. Standard tissue or cell-block testing for EGFR, ALK, and ROS1 identified 20 mutations (51.3%), whereas PE cfDNA identified 25 mutations (64.1%). Five EGFR mutations were observed in PE cfDNA but not in Cobas EGFR owing to coverage or insufficient tumor content issues. The overall rate of oncogenic mutations identified in the PE cfDNA was 92.3%, and the mutation distribution was as follows: even with a very low cfDNA input, high detection rates could be achieved. Otherwise, most patients harbored co-mutations. Comparison of pleural fluid NGS with traditional testing revealed differences in accuracy. We also followed up with patients with EGFR-sensitizing mutations who had a treatment response rate of 97.2% after 3 months., Conclusions: Genotyping of MPE supernatant cfDNA is feasible in clinical practice, in addition to plasma and tumor testing, to improve diagnostic yield and extend patients' benefit from targeted therapies., (© 2024. The Author(s).)

Background: Dual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups., Methods: The TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed., Results: Data from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study., Conclusions: The three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution., (© 2024. The Author(s).)

Background: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions., Methods: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales., Results: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006)., Conclusions: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread inflammation and multi-organ damage. Toll-like receptor 7 (TLR-7) and autophagy have been implicated in SLE pathogenesis. Rice husk silica liquid (RHSL) has shown potential for modulating inflammatory responses, but its effects on SLE have not been thoroughly investigated. This study aims to evaluate the impact of RHSL on immune responses and autophagy in cell culture experiments, focusing on its effects on TLR-7 signaling, cytokine production, and autophagy modulation. RAW264.7 cells and human peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients were used. Cells were stimulated with LPS or TLR-7 agonists and treated with RHSL. Cell viability was assessed, and cytokine levels (TNF-α and IL-6) were measured by ELISA. Autophagy-related proteins (LC3II, ATG5-ATG12) were analyzed by Western blotting. The effect of autophagy inhibition was studied using 3-methyladenine (3-MA). A concentration of 100 μg/mL RHSL did not affect cell viability but significantly reduced the TNF-α production in TLR-7 agonist-stimulated RAW264.7 cells (compared to TLR-7 alone, 3.41 ± 0.54 vs. 6.72 ± 0.07 folds) and PBMCs (compared to TLR-7 alone, 0.97 ± 0.19 vs. 1.40 ± 0.33 folds). RHSL enhanced autophagy, as evidenced by increased LC3II (4.35 ± 1.08 folds) and ATG5-ATG12 (7.07 ± 1.30 folds) conjugation in both RAW264.7 cells and SLE patient-derived PBMCs. The reduction in TNF-α production by RHSL was attenuated by 3-MA, indicating that autophagy plays a role in this process. RHSL also inhibited the translocation of phosphorylated NF-κB into the nucleus, suggesting a mechanism for its anti-inflammatory effects. RHSL exhibits potential as an immunomodulatory agent in SLE by enhancing autophagy and modulating TLR-7 signaling pathways. These findings suggest that RHSL could offer therapeutic benefits for managing inflammatory responses in SLE and warrant further investigation into its clinical applications.

Divergent synthesis of structurally different products from the same kinds of starting materials is highly synthetically useful but very challenging. Herein, we reported a base-mediated chemodivergent [4 + 1] and [2 + 1] cycloaddition of N -alkylpyridinium and enone under mild conditions, leading to furan-fused bicycles with high diastereoselectivity and spirobicycles, respectively, from moderate to high yields. N -Alkylpyridinium salts were modular nucleophilic transfer reagents and C1 synthons, which underwent tandem Michael addition to the α,β-unsaturated ketones and cyclization under the base conditions. Late-stage derivatization of 4-propyldicyclohexylanone from an important industrial raw of liquid crystal display (LCD) screens was realized. In vitro , compound 3f exhibited good activities against human colon cancer cells (HCT116) with IC 50 values in 9.82 ± 0.27 μM. Further biological evaluations investigated the mechanism of the effective inhibition of cell growth, including apoptosis ratio detection, cell cycle analysis, and migration capacity of HCT116 cells. In apoptosis effect studies, complex 3f increased the percentage of apoptotic HCT116 cells to 26.8% (15 μM).

Background & Aims: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality., Methods: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries., Results: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68)., Conclusions: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals., Impact and Implications: While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background : Previous studies on the association between diet quality and ovarian cancer (OC) survival are limited and inconsistent. We evaluated the relationship between pre- and post-diagnosis diet quality based on the Healthy Eating Index-2020 (HEI-2020), as well as their changes and OC survival. Methods : This prospective cohort study involved 1082 patients with OC aged 18-79 years, enrolled between 2015 and 2022. Detailed dietary intake before and after diagnosis was recorded using a validated food frequency questionnaire. Deaths were ascertained until February 16th, 2023 via medical records and active follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results : We included 549 OC cases with a median follow-up of 44.9 months, representing 206 total deaths. Higher HEI scores were associated with better OS (pre-diagnosis: HR T3 vs. T1 0.66, 95%CI: 0.46-0.93, HR 1-SD 0.84, 95%CI: 0.73-0.96; post-diagnosis: HR T3 vs. T1 0.68, 95%CI: 0.49-0.96, HR 1-SD 0.80, 95%CI: 0.69-0.92). Compared to the stable group, the group with decreased HEI scores (>3%) from pre- to post-diagnosis had worse OS (HR 1.93, 95%CI: 1.26-2.97). Conclusion : High pre- and post-diagnosis diet quality was associated with improved OC survival, whereas deterioration in diet quality after diagnosis was associated with decreased OC survival.

To explore and utilize the abundant soil microorganisms and their beneficial functions, high-throughput sequencing technology was used to analyze soil microbial compositions in the rhizosphere of red and green amaranth varieties. The results showed that significant differences in soil microbial composition could be found in the rhizosphere of amaranth plants with different color phenotypes. Firstly, soil bacterial compositions in the rhizosphere were significantly different between red and green amaranths. Among them, Streptomyces, Pseudonocardia , Pseudolabrys , Acidibacter, norank&#95; f&#95; Micropepsaceae , Bradyrhizobium , and Nocardioides were the unique dominant soil bacterial genera in the rhizosphere of red amaranth. In contrast, Conexibacter , norank&#95;f&#95;norank&#95;o&#95;norank&#95;c&#95;TK10 , and norank&#95;f&#95; norank&#95;o&#95; norank&#95; c&#95;AD3 were the special dominant soil bacterial genera in the rhizosphere of green amaranth. Additionally, even though the soil fungal compositions in the rhizosphere were not significantly different between red and green amaranths, the abundance of the dominant soil fungal genera in the rhizosphere showed significant differences between red and green amaranths. For example, unclassified&#95;k&#95;&#95;Fungi , Fusarium , Cladophialophora , unclassified&#95;c&#95;&#95;Sordariomycetes and unclassified&#95;p&#95;&#95;Chytridiomycota significantly enriched as the dominant soil fungal genera in the rhizosphere of the red amaranth. In contrast, Aspergillues only significantly enriched as the dominant soil fungal genus in the rhizosphere of green amaranth. All of the above results indicated that amaranth with various color phenotypes exactly recruited different microorganisms in rhizosphere, and the enrichments of soil microorganisms in the rhizosphere could be speculated in contributing to amaranth color formations.

Background: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking., Methods: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression., Results: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively., Limitation: The generalizability to other ethnic groups is limited., Conclusion: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied., Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed., Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [ P = .03%] and 1.0% vs 3.8% [ P = .05], respectively)., Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Tin oxide is a promising channel material, offering the advantages of being low-cost and environmentally friendly and having a wide band gap. However, despite the high electron mobility of SnO 2 in bulk, the corresponding thin-film transistors (TFTs) generally exhibit moderate performance, hindering their widespread application. Herein, we proposed a codoping strategy to improve both the electrical property and the stability of SnO 2 TFTs. A comparative analysis between doped and undoped SnO 2 was conducted. It is observed that taking advantage of the difference in ionic radii between two dopants (indium and gallium) and the tin ions in the host lattice can effectively reduce impurity-induced strain. Additionally, we investigated the effect of codoping content on SnO 2 TFTs. The optimal codoped SnO 2 (TIGO) TFTs demonstrate high performance, featuring a field-effect mobility of 15.9 cm 2 /V·s, a threshold voltage of 0.2 V, a subthreshold swing of 0.5 V/decade, and an on-to-off current ratio of 2.2 × 10 7 . Furthermore, the devices show high stability under both positive and negative bias stress conditions with a small threshold voltage shift of 1.8 and -1.2 V, respectively. Utilizing the TIGO TFTs, we successfully constructed a resistor-loaded unipolar inverter with a high gain of 10.76. This study highlights the potential of codoped SnO 2 TFTs for advanced applications in electronic devices.

Background: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated., Methods: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817)., Results: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence., Conclusion: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.

Introduction: Our objective is to determine whether prolonged infusion (PI) of beta-lactam antibiotics yields superior outcomes compared to intermittent infusion (II) in patients with Gram-Negative Bacterial (GNB) infections., Methods: We systematically searched papers from PubMed, the Cochrane Library, Embase, and Clinicaltrials.gov, targeting mortality as the primary outcome and looking at the clinical cure rate, hospital and intensive care unit (ICU) stay lengths, antibiotic treatment duration, and mechanical ventilation (MV) duration as secondary outcomes., Results: Our meta-analysis of 18 studies, including 5 randomized control trials and 13 observational studies, with a total of 3,035 patients-1,510 in the PI group and 1,525 in the II group, revealed significant findings. PI was associated with reduced mortality (RR, 0.67; 95% CI, 0.55-0.81; p  = 0.001; I 2 = 4.52%) and a shorter MV duration (SMD, -0.76; 95% CI, -1.37 to -0.16; p  = 0.01; I 2  = 87.81%) compared to II. However, no differences were found in clinical cure rates, antibiotic treatment duration, length of hospital stay, or length of ICU stay., Conclusions: The PI approach for administering beta-lactam antibiotics in patients with suspected or confirmed GNB infections may be advantageous in reducing mortality rates and the duration of MV when compared to the II strategy.

Background: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes., Methods: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors., Results: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC., Conclusion: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D., (© 2024. The Author(s).)

Background: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence., Methods: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587)., Results: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index., Conclusion: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases., (© 2024. The Author(s).)

To characterize the chromosomes of the four species of Polygonatum Miller, 1754, used in traditional Chinese medicine, P.cyrtonema Hua, 1892, P.kingianum Collett et Hemsley, 1890, P.odoratum (Miller, 1768) Druce, 1906, and P.sibiricum Redouté, 1811, and have an insight into the karyotype variation of the genus Polygonatum , fluorescence in situ hybridization (FISH) with 5S and 45S rDNA oligonucleotide probes was applied to analyze the karyotypes of 9 populations of the four species. Detailed molecular cytogenetic karyotypes of the 9 populations were established for the first time using the dataset of chromosome measurements and FISH signals of 5S and 45S rDNA. Four karyotype asymmetry indices, CV CI , CV CL , M CA and Stebbins' category, were measured to elucidate the asymmetry of the karyotypes and karyological relationships among species. Comparison of their karyotypes revealed distinct variations in the karyotypic parameters and rDNA patterns among and within species. The basic chromosome numbers detected were x = 9, 11 and 13 for P.cyrtonema , x = 15 for P.kingianum , x = 10 and 11 for P.odoratum , and x = 12 for P.sibiricum . The original basic chromosome numbers of the four species were inferred on the basis of the data of this study and previous reports. All the 9 karyotypes were of moderate asymmetry and composed of metacentric, submetacentric and subtelocentric chromosomes or consisted of two of these types of chromosomes. Seven populations have one locus of 5S rDNA and two loci of 45S rDNA, and two populations added one 5S or 45S locus. The karyological relationships among the four species revealed by comparison of rDNA patterns and PCoA based on x , 2 n , TCL, CV CI , M CA and CV CL were basically accordant with the phylogenetic relationships revealed by molecular phylogenetic studies. The mechanisms of both intra- and inter-specific dysploidy in Polygonatum were discussed based on the data of this study and literature., (Yan-Fang Wei, Xiang-Hui Jiang, Rong Song, Chao-Wen She.)

Objectives: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China., Methods: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed., Results: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis., Conclusions: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Background: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB)., Methods: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores., Results: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality., Conclusion: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB., (© 2024. The Author(s).)

Background: Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis., Methods: The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry., Results: After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased., Conclusions: In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis., (© 2024. The Author(s).)

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 μmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 μmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

Helicobacter pylori (H. pylori) is a gram-negative bacteria with a worldwide infection rate of 50%, known to induce gastritis, ulcers and gastric cancer. The interplay between H. pylori and immune cells within the gastric mucosa is pivotal in the pathogenesis of H. pylori-related disease. Following H. pylori infection, there is an observed increase in gastric mucosal macrophages, which are associated with the progression of gastritis. H. pylori elicits macrophage polarization, releases cytokines, reactive oxygen species (ROS) and nitric oxide (NO) to promote inflammatory response and eliminate H. pylori. Meanwhile, H. pylori has developed mechanisms to evade the host immune response in order to maintain the persistent infection, including interference with macrophage phagocytosis and antigen presentation, as well as induction of macrophage apoptosis. Consequently, the interaction between H. pylori and macrophages can significantly impact the progression, pathogenesis, and resolution of H. pylori infection. Moreover, macrophages are emerging as potential therapeutic targets for H. pylori-associated gastritis. Therefore, elucidating the involvement of macrophages in H. pylori infection may provide novel insights into the pathogenesis, progression, and management of H. pylori-related disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Reports of tuberculosis (TB) during anticancer treatment with immune checkpoint inhibitors (ICIs) are increasing. However, it is not clear whether the use of ICIs is a significant risk factor for TB, including reactivation or latent TB infection (LTBI)., Methods: To determine the risk of TB reactivation in patients with lung cancer who use ICIs or tyrosine kinase inhibitors (TKIs), we conducted a retrospective study using a hospital-based cancer registry. In addition, we monitored patients with cancer using ICI or TKI in a multicenter prospective study to check the incidence of LTBI., Results: In the retrospective study, several demographic factors were imbalanced between the ICI and TKI groups: the ICI group was younger, had more males, exhibited more squamous cell carcinoma in histology rather than adenocarcinoma, had fewer EGFR mutations, and received more chemotherapy. Propensity score matching was used to control for confounding factors, and we found that the incidence of TB was higher among patients with lung cancer who received ICIs than among those who received TKIs (2298 vs 412 per 100 000 person-years, P = .0165). Through multivariable analysis, group (ICI vs TKI) was the independent risk factor for TB development (adjusted hazard ratio (aHR): 6.29, 95% CI, 1.23-32.09, P = .0269). In the prospective cohort, which included 72 patients receiving ICIs and 50 receiving TKIs, we found that the incidence of positive seroconversion of LTBI by interferon gamma release assay (IGRA) was significantly higher in patients receiving ICIs (18% vs 0%, aHR: 9.88, P = 0.035) under multivariable Cox regression., Conclusion: The use of ICIs may be linked to a higher likelihood of TB reactivation and LTBI than individuals solely receiving TKIs as anticancer therapy. Consequently, the implementation of a screening program for TB reactivation and LTBI among patients undergoing ICI treatment could prove advantageous by enabling early detection and prompt treatment of the infection., (© The Author(s) 2024. Published by Oxford University Press.)

Background/purpose: In Taiwan, cone-beam computed tomography (CBCT) has already widely used in dentistry. This study explored preliminarily the usage of dental CBCT during the COVID-19 pandemic (from 2020 to 2022) through a survey of a regional hospital in the northern Taiwan., Materials and Methods: This study used purposeful sampling to select a regional hospital in the northern Taiwan to survey its usage of dental CBCT during the COVID-19 pandemic., Results: In the surveyed hospital, the number of patients' visits for the usage of dental CBCT increased from 355 in 2020 to 449 in 2021 and further to 488 in 2022 with a growth rate of 37.46 %, while the growth rates compared to the previous year were 26.48 % in 2021 and 8.69 % in 2022, respectively. There were a total of 1292 patients' visits for the dental CBCT. The ages of the 1292 patients (573 males and 719 females) ranged from 4 to 89 years. The 50-59-year age group had the highest number of patients' visits (371, 28.72 %), followed in a descending order by the 60-69-year (293, 22.68 %) and 40-49-year (206, 15.94 %) age groups. The dental CBCT was used mainly for the assessment of dental implants, accounting for 1148 (78.85 %) of the total 1456 irradiations., Conclusion: During the COVID-19 pandemic, the medical services for dental care and treatments in Taiwan are still maintained normally, and the dental CBCT is also used widely and popularly by the dental patients of all ages, various dental procedures, and various dental specialties., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)