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Xin Xue,1 Zhe Zhao,2 Li-Bo Zhao,2 Ying-Hui Gao,3 Wei-Hao Xu,4 Wei-Meng Cai,5 Shao-Hua Chen,5 Tian-Jiao Li,6 Ting-Yu Nie,6 Dong Rui,5 Yao Ma,5 Xiao-Shun Qian,1 Jun-Ling Lin,7 Lin Liu1 1Department of Pulmonary and Critical Care Medicine of the Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Vasculocardiology, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3PKU-Upenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of China; 4Department of Geriatrics, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 6Medical College, Yan’ an University, Yan’ an, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Lin Liu, Department of Pulmonary and Critical Care Medicine of the Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China, Email liulin715@qq.com Jun-Ling Lin, Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, 100020, People’s Republic of China, Email 18611521849@163.comBackground: Previous studies have demonstrated a significant correlation between obstructive sleep apnea (OSA) and frailty. However, the association of mean pulse oxygen saturation (MSpO2) with frailty among OSA patients remains unconfirmed. This study aimed to explore this potential association using data from a multicenter, prospective cohort.Methods: A total of 1006 elderly patients diagnosed with OSA through polysomnography (PSG) from January 2015 to October 2017 were enrolled. Patients were stratified into four groups according to their MSpO2 levels to assess differences in frailty onset. Multivariate Cox regression analysis, Kaplan-Meier curves, restricted cubic splines, and subgroup analyses were employed to evaluate variations in frailty onset across different MSpO2 levels.Results: Over a median follow-up period of 52 months, 275 patients developed frailty. Analysis using restricted cubic splines revealed a U-shaped trend between MSpO2 and frailty risk (non-linear p-value = 0.028). Patients in the lowest quartile (MSpO2

Xin Xue,1,2 Li-Bo Zhao,3 Zhe Zhao,3 Wei-Hao Xu,4 Wei-Meng Cai,1 Shao-Hua Chen,1 Tian-Jiao Li,5 Ting-Yu Nie,5 Dong Rui,1 Xiao-Shun Qian,1 Lin Liu1 1Department of Pulmonary and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Vasculocardiology, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Geriatrics, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 5Medical College, Yan’ an University, Yan’ an, People’s Republic of ChinaCorrespondence: Lin Liu; Xiao-Shun Qian, Department of Pulmonary and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Tel +86 132 6318 9578 ; +86 135 2127 9287, Email liulin715@qq.com; 13521279287@163.comBackground: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored.Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA.Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15– 0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19– 0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14– 0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19– 0.75; P = 0.007).Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.Keywords: obstructive sleep apnea, frailty, continuous positive airway pressure, elderly

Si-Wen Gui,1,2,* Yi-Yun Liu,1–3,* Xiao-Gang Zhong,1,2,4,* Xinyu Liu,5,* Peng Zheng,1–3 Jun-Cai Pu,1–3 Jian Zhou,1,2 Jian-Jun Chen,1,2 Li-Bo Zhao,6 Lan-Xiang Liu,1–3 Guowang Xu,5 Peng Xie1–3 1Chongqing Key Laboratory of Neurobiology, Chongqing, China; 2Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; 3Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 4School of Public Health and Management, Chongqing Medical University, Chongqing, China; 5CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; 6Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Introduction: Major depressive disorder (MDD) is a highly prevalent mental disorder affecting millions of people worldwide. However, a clear causative etiology of MDD remains unknown. In this study, we aimed to identify critical protein alterations in plasma from patients with MDD and integrate our proteomics and previous metabolomics data to reveal significantly perturbed pathways in MDD. An isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach was conducted to compare plasma protein expression between patients with depression and healthy controls (CON). Methods: For integrative analysis, Ingenuity Pathway Analysis software was used to analyze proteomics and metabolomics data and identify potential relationships among the differential proteins and metabolites. Results: A total of 74 proteins were significantly changed in patients with depression compared with those in healthy CON. Bioinformatics analysis of differential proteins revealed significant alterations in lipid transport and metabolic function, including apolipoproteins (APOE, APOC4 and APOA5), and the serine protease inhibitor. According to canonical pathway analysis, the top five statistically significant pathways were related to lipid transport, inflammation and immunity. Conclusion: Causal network analysis by integrating differential proteins and metabolites suggested that the disturbance of phospholipid metabolism might promote the inflammation in the central nervous system. Keywords: major depressive disorder, plasma proteomics, iTRAQ, metabolomics, integrative analysis

Bin Qin,1,* Hong Chen,1,* Wen Gao,1,* Li-Bo Zhao,2,* Ming-Jun Zhao,3 Hui-Xun Qin,1 Ming-Xiu Yang1 1Department of Neurology, Affiliated Liuzhou People’s Hospital of Guangxi University of Science and Technology/Liuzhou People’s Hospital, Liuzhou, 2Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 3Department of Pharmacy, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, China *These authors contributed equally to this work Aim: This meta-analysis aimed to assess the effect of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) for the treatment of depression in patients with Parkinson’s disease (PD). Methods: The design was a meta-analysis of randomized controlled trials (RCTs). The participants were patients with PD who suffered from depression. The interventions were HF-rTMS alone or in combination with other treatments compared with sham-rTMS, placebo, and antidepressant treatments. The primary outcome measure was changes in depressive symptoms, defined as the mean change in the total depression score. The secondary outcome was changes in motor symptoms, defined by Unified Parkinson’s Disease Rating Scale part III scores, and the acceptability, defined as the risk of all-cause discontinuation. These were expressed as mean differences (MDs), standardized mean differences (SMDs), or risk ratios (RRs) with 95% confidence intervals (CIs). Results: We identified nine suitable trials, with data from 332 participants. For the patients with depression in PD, HF-rTMS was not better than sham-rTMS (SMD =-0.33, 95% CI -0.83 to 0.17) or selective serotonin re-uptake inhibitors (SSRIs) (SMD =0.07, 95% CI -0.52 to 0.18) for the treatment of depressive symptoms. However, the motor benefits after treatment with HF-rTMS might be better than sham-rTMS (MD =-2.80, 95% CI -5.45 to -0.15) and SSRIs (MD =-2.70, 95% CI -4.51 to -0.90). Conclusion: This meta-analysis provides some evidence that in patients with PD with depression, HF-rTMS may lead to improvement in motor function but not in depression compared with sham-rTMS or SSRIs. Keywords: sham-repetitive transcranial magnetic stimulation, selective serotonin re-uptake inhibitors, depressive symptoms, motor symptoms

Jiapeng Li,1,2 Yang Liu,2 Jingru Zhang,1,2 Xiaotong Yu,1,2 Xiaoling Wang,1 Libo Zhao11Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Background: The intestinal cytochrome P450 3A (CYP 3A) and P-glycoprotein (P-gp) present a barrier to the oral absorption of saquinavir (SQV). Resveratrol (RESV) has been indicated to have modulatory effects on P-gp and CYP 3A. Therefore, this study was to investigate the effects of RESV on P-gp and CYP 3A activities in vitro and in vivo on oral SQV pharmacokinetics in rats.Methods: In vitro, intestinal microsomes were used to evaluate RESV effect on CYP 3A-mediated metabolism of SQV; MDR1-expressing Madin–Darby canine kidney (MDCKII-MDR1) cells were employed to assess the impact of RESV on P-gp-mediated efflux of SQV. In vivo effects were studied using 10 rats randomly assigned to receive oral SQV (30 mg/kg) with or without RESV (20 mg/kg). Serial blood samples were obtained over the following 24 h. Concentrations of SQV in samples were ascertained using high-performance liquid chromatography-tandem mass spectrometry analysis.Results: RESV (1–100 µM) enhanced residual SQV (% of control) in a dose-dependent manner after incubation with intestinal microsomes. RESV (1–100 µM) reduced the accumulation of SQV in MDCKII-MDR1 cells in a concentration-dependent manner. A double peaking phenomenon was observed in the plasma SQV profiles in rats. The first peak of plasma SQV concentration was increased, but the second peak was reduced by coadministration with RESV. The mean AUC0–∞ of SQV was slightly decreased, with no statistical significance probably due to the high individual variation.Conclusion: RESV can alter the plasma SQV concentration profiles, shorten the Tmax of SQV. RESV might also cause a slight decrease tendency in the SQV bioavailability in rats. Keywords: resveratrol, saquinavir, P-glycoprotein, CYP 3A, pharmacokinetic

Boran Cheng,1,* Zhaobo He,2,* Libo Zhao,2,* Yuan Fang,1 Yuanyuan Chen,1 Rongxiang He,2 Fangfang Chen,1 Haibin Song,1 Yuliang Deng,2 Xingzhong Zhao,2 Bin Xiong1 1Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei, People’s Republic of China; 2Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Abstract: Circulating tumor cells (CTCs) in the blood which have detached from both the primary tumor and any metastases may be considered as a “liquid biopsy” and are expected to replace tumor biopsies in the monitoring of treatment response and determining patient prognosis. Here, we introduce a facile and efficient CTC detection material made of hydroxyapatite/chitosan (HA/CTS), which is beneficial because of its transparency and excellent biological compatibility. Atomic force microscopy images show that the roughness of the HA/CTS nanofilm (HA/CTSNF) substrates can be controlled by changing the HA:CTS ratio. Enhanced local topographic interactions between nano-components on cancer cell membranes, and the antibody coated nanostructured substrate lead to improved CTC capture and separation. This remarkable nanostructured substrate has the potential for CTC culture in situ and merits further analysis. CTCs captured from artificial blood samples were observed in culture on HA/CTSNF substrates over a period of 14 days by using conventional staining methods (hematoxylin eosin and Wright’s stain). We conclude that these substrates are multifunctional materials capable of isolating and culturing CTCs for subsequent studies. Keywords: cell capture, cell culture, nanofilms, hydroxyapatite/chitosan

Background: Previous studies have demonstrated a significant correlation between obstructive sleep apnea (OSA) and frailty. However, the association of mean pulse oxygen saturation (MSpO 2 ) with frailty among OSA patients remains unconfirmed. This study aimed to explore this potential association using data from a multicenter, prospective cohort., Methods: A total of 1006 elderly patients diagnosed with OSA through polysomnography (PSG) from January 2015 to October 2017 were enrolled. Patients were stratified into four groups according to their MSpO 2 levels to assess differences in frailty onset. Multivariate Cox regression analysis, Kaplan-Meier curves, restricted cubic splines, and subgroup analyses were employed to evaluate variations in frailty onset across different MSpO 2 levels., Results: Over a median follow-up period of 52 months, 275 patients developed frailty. Analysis using restricted cubic splines revealed a U-shaped trend between MSpO 2 and frailty risk (non-linear p- value = 0.028). Patients in the lowest quartile (MSpO 2  < 91.6%) exhibited a higher risk of frailty (hazard ratio [HR] = 1.43, 95% confidence interval [CI] 1.03-1.97, P = 0.029) compared to those in the third quartile (MSpO 2 93-95%). Subgroup and sensitivity analyses confirmed the robustness of the U-shaped relationship., Conclusion: There is a U-shaped association between MSpO 2 and frailty among patients with OSA. Enhancing MSpO 2 levels may mitigate the risk of frailty and improve prognosis in this population., Competing Interests: There were no potential conflicts of interest in the study, according to the authors., (© 2024 Xue et al.)