Publications by authors named "Chengping Hu"

197 Publications

Asthma Management Using the Mobile Asthma Evaluation and Management System in China.

Allergy Asthma Immunol Res 2022 Jan;14(1):85-98

Department of Pulmonary and Critical Care Medicine, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, China.

Purpose: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma.

Methods: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174).

Results: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group.

Conclusions: Mobile asthma management can improve adherence and asthma control compared to traditional management.

Trial Registration: ClinicalTrials.gov Identifier: NCT02917174.
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http://dx.doi.org/10.4168/aair.2022.14.1.85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724822PMC
January 2022

Discovery of tumor immune infiltration-related snoRNAs for predicting tumor immune microenvironment status and prognosis in lung adenocarcinoma.

Comput Struct Biotechnol J 2021 25;19:6386-6399. Epub 2021 Nov 25.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.

Lung adenocarcinoma (LUAD) has a high mortality rate and is difficult to diagnose and treat in its early stage. Previous studies have demonstrated that small nucleolar RNAs (snoRNAs) play a critical role in tumor immune infiltration and the development of a variety of solid tumors. However, there have been no studies on the correlation between tumor-infiltrating immune-related snoRNAs (TIISRs) and LUAD. In this study, we filtered six immune-related snoRNAs based on the tissue specificity index (TSI) and expression profile of all snoRNAs between all LUAD cell lines from the Cancer Cell Line Encyclopedia and 21 types of immune cells from the Gene Expression Omnibus database. Further, we performed real-time quantitative polymerase chain reaction (RT-qPCR) to validate the expression status of these snoRNAs on peripheral blood mononuclear cells (PBMCs) and lung cancer cell lines. Next, we developed a TIISR signature based on the expression profiles of snoRNAs from 479 LUAD patients filtered by the random survival forest algorithm. We then analyzed the value of this TIISR signature (TIISR risk score) for assessing tumor immune infiltration, immune checkpoint inhibitor (ICI) treatment response, and the prognosis of LUAD between groups with high and low TIISR risk score Further we found that the TIISR risk score groups showed significant differences in biological characteristics and that the risk score could be used to assess the level of tumor immune cell infiltration, thereby predicting prognosis and responsiveness to immunotherapy in LUAD patients.
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http://dx.doi.org/10.1016/j.csbj.2021.11.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649667PMC
November 2021

The Potential Impact of Childhood Traumatic Experiences on Coping Styles and Emotion Regulation of Nurse Practitioners During the COVID-19 Outbreak.

Front Psychol 2021 26;12:718780. Epub 2021 Oct 26.

Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.

During an epidemic of a novel infectious disease, frontline medical staff suffer from high psychological stress. Previous studies have found that traumatic childhood experiences are associated with mental and physical health in adulthood. Anxiety and depression were measured and analyzed in relation to childhood trauma and coping styles. This study aims to explore the correlational study between traumatic childhood experiences and coping styles among nurse practitioners. This study sampled 278 nurse practitioners from hospitals designated for the treatment of the novel coronavirus in Sichuan Province. The study measures included the Simplified Coping Style Questionnaire and the Childhood Trauma Questionnaire-Short Form. This research intends to use correlational study methods to explore the relationship between the two factors. Statistical analysis showed that there was no statistically significant difference in the general demographic data between the two groups. Childhood traumatic experiences have a significant impact on the active coping of nurse practitioners, and active coping may be emotionally protective for nurse practitioners.
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http://dx.doi.org/10.3389/fpsyg.2021.718780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576184PMC
October 2021

Association between the triglyceride glucose index and coronary collateralization in coronary artery disease patients with chronic total occlusion lesions.

Lipids Health Dis 2021 Oct 25;20(1):140. Epub 2021 Oct 25.

Department of cardiology, Beijing AnZhen Hospital, Capital Medical University, 100029, Beijing, China.

Background: Recent studies have substantiated the role of the triglyceride glucose (TyG) index in predicting the prognosis of coronary artery disease (CAD) patients, while no relevant studies have revealed the association between the TyG index and coronary collateralization in the event of coronary chronic total occlusion (CTO). The current study intends to explore whether, or to what extent, the TyG index is associated with impaired collateralization in CAD patients with CTO lesions.

Methods: The study enrolled 1093 CAD patients undergoing cardiac catheterization for at least one CTO lesion. Data were collected from the Beijing Anzhen Hospital record system. The degree of collaterals was determined according to the Rentrop classification system. The correlation between the TyG index and coronary collateralization was assessed.

Results: Overall, 318 patients were included in a less developed collateralization (Rentrop classification 0-1) group. The TyG index was significantly higher in patients with impaired collateralization (9.3±0.65 vs. 8.8±0.53, P<0.001). After adjusting for various confounding factors, the TyG index remained correlated with the occurrence of impaired collateralization, with odds ratios (ORs) of 1.59 and 5.72 in the T2 and T3 group compared with the first tertile group (P<0.001). In addition, subgroup analysis showed that higher TyG index values remained strongly associated with increased risk of less developed collateralization. To compare the risk assessment efficacy for the formation of collateralization between the TyG index and other metabolic abnormality indicators, an area under the receiver-operating characteristic (ROC) curve (AUC) was obtained. A significant improvement in the risk assessment performance for impaired collateralization emerged when adding the TyG index into a baseline model.

Conclusions: The increased TyG index is strongly associated with less developed collateralization in CAD patients with CTO lesions and its risk assessment performance is better than single metabolic abnormality indicators.
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http://dx.doi.org/10.1186/s12944-021-01574-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543811PMC
October 2021

Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407.

JTO Clin Res Rep 2021 Oct 25;2(10):100225. Epub 2021 Sep 25.

Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.

Introduction: Pembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies.

Methods: Patients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel. Dual primary end points were overall survival (OS) and progression-free survival (PFS) (based on the Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review).

Results: A total of 125 patients were randomized (pembrolizumab-chemotherapy, n = 65; placebo-chemotherapy, n = 60). As of September 30, 2020, median (range) study follow-up was 28.1 (25.1‒40.9) months. Pembrolizumab-chemotherapy improved OS (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.28-0.70) and PFS (HR = 0.35, 95% CI: 0.24-0.52) versus placebo-chemotherapy. Two-year OS and PFS rates for pembrolizumab-chemotherapy versus placebo-chemotherapy were 56.9% versus 31.7% and 24.2% versus 3.3%, respectively. Treatment-related grade 3 to 5 adverse events occurred in 81.5% and 81.7%, respectively. Relative to baseline, pembrolizumab-chemotherapy improved global health status/quality of life scores at week 18 versus placebo-chemotherapy (difference in least squares means = 7.6, 95% CI: 1.5-13.7) and prolonged time to deterioration in cough, chest pain, or dyspnea (HR = 0.50, 95% CI: 0.28-0.89).

Conclusions: Pembrolizumab-chemotherapy prolonged survival versus placebo-chemotherapy with manageable toxicity and preserved or improved health-related quality of life in Chinese patients with metastatic squamous NSCLC. These findings support pembrolizumab-chemotherapy as first-line therapy in this population.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503629PMC
October 2021

A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance.

Front Oncol 2021 1;11:722039. Epub 2021 Oct 1.

Department of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.

Background: proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with -mutant non-small-cell lung cancer (NSCLC) who were detected with amp at EGFR-TKI progression using next-generation sequencing.

Methods: Of the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.

Results: The objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 . 2.3 . 2.9 months, p = 0.010), but overall survival was comparable (10.0 . 4.1 . 8.5 months, p = 0.088). mutation (58.5%) and amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent mutation (n = 17) (6.0 . 2.3 . 2.9 months, p = 0.009) or amp (n = 13) (5.0 . 1.2 . 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included -T790M (n = 2), L718Q (n = 1), -S645C (n = 1), -D1228H (n = 1), -V600E (n = 1), -Q61H (n = 1), amp (n = 1), amp (n = 1), amp (n = 1), and amp (n = 1).

Conclusion: Our study provides real-world clinical evidence from a large cohort that simultaneous inhibition of and could be a more effective therapeutic strategy for patients with amp acquired from EGFR-TKI therapy.
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http://dx.doi.org/10.3389/fonc.2021.722039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517073PMC
October 2021

Lung cancer-associated T cell repertoire as potential biomarker for early detection of stage I lung cancer.

Lung Cancer 2021 Dec 28;162:16-22. Epub 2021 Sep 28.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China. Electronic address:

Background: Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer.

Methods: Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs).

Results: A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96).

Conclusion: This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts.
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http://dx.doi.org/10.1016/j.lungcan.2021.09.017DOI Listing
December 2021

The Predictive Values of Advanced Non-Small Cell Lung Cancer Patients Harboring Uncommon Mutations-The Mutation Patterns, Use of Different Generations of -TKIs, and Concurrent Genetic Alterations.

Front Oncol 2021 26;11:646577. Epub 2021 Aug 26.

Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China.

Introduction: Epidermal growth factor receptor () and mutation are known as "common mutations" in non-small cell lung cancer (NSCLC) and predict sensitivities to tyrosine kinase inhibitors (TKIs), whereas and mutations confer drug-resistance to -TKIs. The role of the remaining uncommon mutations remains elusive.

Methods: We retrospectively screened a group of NSCLC patients with uncommon mutations other than and . The mutation patterns, use of different generations of -TKIs, and concurrent genetic alterations were analyzed. Meanwhile, a cohort of patients with single or were included for comparison.

Results: A total of 180/1,300 (13.8%) patients were identified. There were 102 patients with advanced or recurrent NSCLC that received first-line therapy of gefitinib/erlotinib/icotinib and afatinib and were eligible for analysis. The therapeutic outcomes among patients with common mutations (cm, n = 97), uncommon mutation plus common mutations (um+cm, n = 52), complex uncommon mutations (complex um, n = 22), and single uncommon mutations (single um, n = 28) were significantly different (ORRs: 76.3%, 61.5%, 54.5%, and 50.0%, respectively, p = 0.023; and mPFS: 13.3, 14.7, 8.1, and 6.0 months, respectively, p = 0.004). Afatinib showed superior efficacy over gefitinib/erlotinib/icotinib in cm (ORR: 81.0% . 75.0%, p = 0.773; mPFS: 19.1 . 12.0m, p = 0.036), um+cm (ORR: 100% . 54.5%, p = 0.017; mPFS: NE . 13.6m, p = 0.032), and single um (ORR: 78.6% . 21.4%, p = 0.007; mPFS: 10.1 . 3.0m, p = 0.025) groups. Comprehensive genomic profiling by Next Generation Sequencing encompassing multiple cancer-related genes was performed on 51/102 patients; the mPFS of patients without co-mutation (n = 16) and with co-mutations of tumor-suppressor genes (n = 31) and driver oncogenes (n = 4) were 31.1, 9.2, and 12.4 months, respectively (p = 0.046). mutation was the most common co-alteration and showed significantly shorter mPFS than wild-type patients (7.0 . 31.1m, p < 0.001). Multivariate analysis revealed that concurrent and tumor-suppressor gene alterations independently predicted better and worse prognosis in patients with uncommon mutations, respectively.

Conclusions: Uncommon mutations constitute a highly heterogeneous subgroup of NSCLC that confer different sensitivities to -TKIs with regard to the mutation patterns. Afatinib may be a better choice for most uncommon mutations. Concurrent and tumor-suppressor gene alterations, especially , can be established as prognostic biomarkers.
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http://dx.doi.org/10.3389/fonc.2021.646577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426345PMC
August 2021

Perivascular Adipose-Derived Exosomes Reduce Foam Cell Formation by Regulating Expression of Cholesterol Transporters.

Front Cardiovasc Med 2021 19;8:697510. Epub 2021 Aug 19.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China.

Accumulating evidence demonstrates that perivascular adipose tissue (PVAT) plays an important role in maintaining vascular homeostasis. The formation of macrophage foam cells is a central feature of atherosclerosis. This study aimed to evaluate the effect of PVAT-derived exosomes (EXOs) on the lipid accumulation of macrophages and verify the anti-atherogenic characteristics of PVAT. We extracted EXOs from the PVAT and subcutaneous adipose tissue (SCAT) of wild-type C57BL/6J mice. After coincubation, the EXOs were taken up by RAW264.7 cells. Oil Red O staining revealed that macrophage foam cell formation and intracellular lipid accumulation were ameliorated by PVAT-EXOs. Flow cytometry showed that PVAT-EXOs significantly reduced macrophage uptake of fluorescence-labelled oxidised low-density lipoprotein (ox-LDL). In addition, high-density lipoprotein-induced cholesterol efflux was promoted by PVAT-EXOs. Western blot analysis showed the downregulation of macrophage scavenger receptor A and the upregulation of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which could be mediated by the overexpression of peroxisome proliferator-activated receptor γ and was independent of liver X receptor α. Our findings suggest that PVAT-EXOs reduce macrophage foam cell formation by regulating the expression of cholesterol transport proteins, which provides a novel mechanism by which PVAT protects the vasculature from atherosclerosis.
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http://dx.doi.org/10.3389/fcvm.2021.697510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416751PMC
August 2021

Influence of Family Dynamics on Stigma Experienced by Patients With Schizophrenia: Mediating Effect of Quality of Life.

Front Psychiatry 2021 17;12:645075. Epub 2021 Aug 17.

Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.

Stigma is a barrier to schizophrenia recovery; thus, screening the factors that affect stigma experienced by patients with schizophrenia and exploring the interactions between each factor are critical for improved treatment. The purpose of this study was to demonstrate the relationship between quality of life (QoL), family dynamics, and stigma in patients with schizophrenia. A total of 447 participants with schizophrenia were recruited in the study, namely, 281 community patients and 166 inpatients. Three scales, Schizophrenia Quality of Life Scale (SQLS), Self-rating Scale of Systemic Family (SSFD), and Stigma Scale for Mental Illness (SSMI), were, respectively, used to evaluate three variables: QoL, family dynamics, and stigma. The correlations between each factor in these three scales were evaluated by Spearman's rank correlation analysis. A mediation model was constructed to investigate whether QoL mediated the relationship between stigma and family dynamics. Correlation analysis revealed that most variables in these three scales correlated significantly with each other. Mediational regression analyses indicated that the degree of stigma was affected by family dynamics; that is, good family dynamics predicted less stigma. Surprisingly, we found that a worse QoL was associated with less stigma, and this led to good family dynamics being related to a worse QoL. These findings further suggested that QoL had a mediating effect on the relationship between family dynamics and stigma. This study suggested that more attention should be focused on the multifactorial influence of stigma on patients with schizophrenia. Integrated and personalized interventions regarding QoL and family dynamics can be tailored for patients with schizophrenia to reduce self-stigma.
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http://dx.doi.org/10.3389/fpsyt.2021.645075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415875PMC
August 2021

Prevalence and Risk Factors for Cognitive Frailty in Aging Hypertensive Patients in China.

Brain Sci 2021 Jul 30;11(8). Epub 2021 Jul 30.

Division of Medical Humanities and Behavioral Sciences, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China.

Hypertension is one of the most common chronic diseases and a major risk factor for stroke, myocardial infarction and cardiovascular death. Cognitive frailty is an important predictor of all-cause mortality and dementia in aging individuals. Hypertension is closely related to cognitive frailty and these two conditions often coexist in aging individuals. Few studies have explored the relationship between hypertension and cognitive frailty in the Chinese population. This study investigates the epidemiological characteristics of and factors related to cognitive frailty in aging Chinese patients with hypertension. In total, cognitive function, weakness, social support, depression and sociodemographic were assessed in 305 participants aged 60 and over. Univariate and multivariate logistic regression models were constructed. The prevalence of cognitive frailty in aging Chinese hypertensive patients was 9.8% (95% CI = 6.4-13.2%). After adjusting for confounding variables, logistic regression showed that the course of hypertension (6-10 years, OR = 8.588, 95% CI = 1.608-45.859;course of more than 10 years, OR = 9.020, 95%CI = 1.854-43.892), multimorbidity (OR = 11.231, 95% CI = 2.912-43.322), depression (OR = 6.917, 95% CI = 2.424-19.738) and social support (OR = 0.187, 95% CI = 0.071-0.492) were independently associated with cognitive frailty. The prevalence of cognitive frailty in aging patients with hypertension in China should not be ignored. The course of hypertension, multimorbidity and depression are the risk factors of cognitive frailty in the aging population and a better level of social support is the protective factor for cognitive frailty.
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http://dx.doi.org/10.3390/brainsci11081018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393928PMC
July 2021

Profilin 1 Protein and Its Implications for Cancers.

Oncology (Williston Park) 2021 07 15;35(7):402-409. Epub 2021 Jul 15.

Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, PR China.

Profilin 1 (PFN1) is a ubiquitous small-molecule protein that exists in all eukaryotes. PFN1 was first identified as a G-actin sequestering molecule, and subsequently, its true functions in actin polymerization and F-actin dynamics were revealed. In the following decades, the structure of PFN1 was recognized to have 3 domains: an actin-binding domain, a poly-L-proline (PLP)-binding domain, and a phosphoinositide-binding domain. PFN1 plays a vital role in many cell functions, including membrane trafficking, endocytosis, cell cycle, motility, proliferation, cell survival, transcription, stemness, and autophagy (Figure 1). Abnormal expression or deletion of PFN1 can affect the normal physiological activity of cells and lead to disease development. PFN1 has been deeply studied in a variety of diseases, some genetic (eg, amyotrophic lateral sclerosis) and some chronic (eg, hypertension). In the past 10 years, PFN1's role in cancer has received increasing attention. In this review, we summarize the studies of PFN1 in cancer that have been completed in recent years, discuss the roles of PFN1 in cancer, and discuss the implications for tumor diagnosis and therapy in the future.
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http://dx.doi.org/10.46883/ONC.2021.3507.0402DOI Listing
July 2021

Triglyceride-glucose index is associated with in-stent restenosis in patients with acute coronary syndrome after percutaneous coronary intervention with drug-eluting stents.

Cardiovasc Diabetol 2021 07 8;20(1):137. Epub 2021 Jul 8.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.

Background: The triglyceride-glucose (TyG) index is an alternative marker of insulin resistance (IR) and is closely associated with the prevalence and prognosis of atherosclerotic cardiovascular disease (ASCVD). However, the association between the TyG index and in-stent restenosis (ISR) after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) remains unknown.

Methods: The present study retrospectively recruited patients who were admitted for ACS and underwent coronary angiography at 6 to 24 months after successful DES-based percutaneous coronary intervention (PCI). In addition, we calculated the TyG index with the following formula: Ln(fasting triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2) and divided patients into 3 groups according to the tertile of the TyG index. Most importantly, multivariate logistic regression analysis models were also constructed to assess the association between the TyG index and DES-ISR in patients with ACS.

Results: A total of 1574 patients with ACS (58.4 ± 9.4 years, 77.4% male) were included in this study. At the median follow-up time of 12 (9-14) months, the prevalence of DES-ISR increased stepwise with the increasing tertile of the TyG index (11.6% vs 17.3% vs 19.4%, p = 0.002), and the TyG index was also higher in the ISR group than in the non-ISR group (9.00 ± 0.58 vs 8.84 ± 0.61, p < 0.001). In addition, the positive association between the TyG index and the prevalence of DES-ISR was also determined in the fully adjusted model (TyG, per 1-unit increase: OR 1.424, 95% CI 1.116 to 1.818, p = 0.005; tertile of TyG, the OR (95% CI) values for tertile 2 and tertile 3 were 1.454 (1.013 to 2.087) and 1.634 (1.125 to 2.374), respectively, with tertile 1 as a reference). The association was also reflected in most subgroups. Moreover, adding the TyG index to the predictive model for DES-ISR in patients with ACS could contribute to an increase in C-statistics (0.675 vs 0.659, p = 0.010), categorical net reclassification improvement (0.090, p < 0.001), and integrated discrimination improvement (0.004, p = 0.040).

Conclusion: An elevated TyG index was independently and positively associated with DES-ISR in patients with ACS who underwent PCI. However, the incremental predictive value of the TyG index for DES-ISR was slight. To further confirm our findings, future studies are needed.
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http://dx.doi.org/10.1186/s12933-021-01332-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268452PMC
July 2021

Anaphylatoxins orchestrate Th17 response via interactions between CD16+ monocytes and pleural mesothelial cells in tuberculous pleural effusion.

PLoS Negl Trop Dis 2021 07 8;15(7):e0009508. Epub 2021 Jul 8.

Department of nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

The complement system is activated in tuberculous pleural effusion (TPE), with increased levels of the anaphylatoxins stimulating pleural mesothelial cells (PMCs) to secrete chemokines, which recruit nonclassical monocytes to the pleural cavity. The differentiation and recruitment of naive CD4+ T cells are induced by pleural cytokines and PMC-produced chemokines in TPE. However, it is unclear whether anaphylatoxins orchestrate CD4+ T cell response via interactions between PMCs and monocytes in TPE. In this study, CD16+ and CD16- monocytes isolated from TPE patients were cocultured with PMCs pretreated with anaphylatoxins. After removing the PMCs, the conditioned monocytes were cocultured with CD4+ T cells. The levels of the cytokines were measured in PMCs and monocyte subsets treated separately with anaphylatoxins. The costimulatory molecules were assessed in conditioned monocyte subsets. Furthermore, CD4+ T cell response was evaluated in different coculture systems. The results indicated that anaphylatoxins induced PMCs and CD16+ monocytes to secrete abundant cytokines capable of only inducing Th17 expansion, but Th1 was feeble. In addition, costimulatory molecules were more highly expressed in CD16+ than in CD16- monocytes isolated from TPE. The interactions between monocytes and PMCs enhanced the ability of PMCs and monocytes to produce cytokines and that of monocytes to express HLA-DR, CD40, CD80 and CD86, which synergistically induced Th17 expansion. In the above process, anaphylatoxins enhanced the interactions between monocytes and PMCs by increasing the level of the cytokines IL-1β, IL-6, IL-23 and upregulating the phenotype of CD40 and CD80 in CD16+ monocytes. Collectively, these data indicate that anaphylatoxins play a central role in orchestrating Th17 response mainly via interactions between CD16+ monocytes and PMCs in TPE.
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http://dx.doi.org/10.1371/journal.pntd.0009508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291687PMC
July 2021

ECMO Rescues Patients With Acute Respiratory Failure Related to GPA.

Front Med (Lausanne) 2021 28;8:671396. Epub 2021 May 28.

Department of Respiratory Medicine (Department of Respiratory and Critical Care Medicine), Xiangya Hospital, Central South University, Changsha, China.

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.
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http://dx.doi.org/10.3389/fmed.2021.671396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192709PMC
May 2021

Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12).

J Thorac Oncol 2021 09 25;16(9):1501-1511. Epub 2021 May 25.

Medical Science and Strategy Oncology, Innovent Biologics Inc., Suzhou, People's Republic of China.

Introduction: The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti-programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP.

Methods: ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People's Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee.

Results: Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422-0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively.

Conclusions: Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.
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http://dx.doi.org/10.1016/j.jtho.2021.04.011DOI Listing
September 2021

Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706).

J Thorac Oncol 2021 09 24;16(9):1533-1546. Epub 2021 May 24.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. Electronic address:

Introduction: Blocking vascular endothelial growth factor pathway can enhance the efficacy of EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC. ACTIVE is the first phase 3 study conducted in the People's Republic of China evaluating apatinib, a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, plus gefitinib as first-line therapy in EGFR-mutant NSCLC.

Methods: Treatment-naive patients with stage IIIB or IV nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and EGFR exon 19 deletion or exon 21 L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/d), plus apatinib (500 mg/d; apatinib [A] + gefitinib [G] group), or placebo (placebo [P] + gefitinib [G] group). Stratification factors were mutation type, sex, and performance status. The primary end point was progression-free survival (PFS) by blinded independent radiology review committee (IRRC). Secondary end points were investigator-assessed PFS, overall survival, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance.

Results: A total of 313 patients were assigned to the A + G (n = 157) or P + G group (n = 156). Median IRRC PFS in the A + G group was 13.7 months versus 10.2 months in the P + G group (hazard ratio 0.71, p = 0.0189). Investigator- and IRRC-assessed PFS were similar. Overall survival was immature. The most common treatment-emergent adverse events greater than or equal to grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A + G group and increased alanine aminotransferase (10.4%) and aspartate aminotransferase (3.2%) in the P + G group. QoL in the two groups had no statistical differences. Post hoc analysis revealed PFS benefits tended to favor the A + G group in patients with TP53 exon 8 mutation.

Conclusions: Apatinib + gefitinib as first-line therapy had superior PFS in advanced EGFR-mutant NSCLC versus placebo + gefitinib. Combination therapy brought more adverse events but did not interfere QoL.

Trial Registration: NCT02824458.
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http://dx.doi.org/10.1016/j.jtho.2021.05.006DOI Listing
September 2021

The Intrapleural Bridge Connection is One of the Reasons for Unknown Localized Pleural Adhesion.

Int J Gen Med 2021 20;14:1429-1435. Epub 2021 Apr 20.

Department of Respiratory Medicine, Xiangya Hospital Affiliated to Central South University, Changsha, Hunan Province, 410008, People's Republic of China.

Background: Simple signs of local pleural adhesion are often found in people during a physical examination. In the present study, we aimed to clarify whether the merely localized pleural adhesion was just caused by previous pleural inflammation or physiological variation.

Materials And Methods: Chest X-ray image materials were collected to analyze the incidence of simple pleural adhesions. Moreover, the causes of these simple pleural adhesions were further analyzed using thoracoscopy under direct vision and biopsy data.

Results: In all 2218 chest X-ray images, 68 cases were found to have pleural lesions (3.07%), including 15 cases of localized pleural adhesion only. Subsequently, we analyzed the characteristics of 70 cases of pleural lesions using thoracoscopy. In two lung cancer patients with pleural metastasis, we found an unusual pleural junction. This connective strip was smooth and free of inflammation, resembling the normal pleura.

Conclusion: Some of these purely localized pleural adhesions might be attributed to previous inflammation. However, there was still at least a possibility that there must be a physiological pleural junction, which could be the cause of the purely localized pleural adhesion shown in the chest radiograph.
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http://dx.doi.org/10.2147/IJGM.S299606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068496PMC
April 2021

The effect of prohibiting outside food during COVID-19 pandemic on the body weight of schizophrenic patients taking olanzapine or clozapine: a retrospective self-controlled study.

Ann Palliat Med 2021 May 19;10(5):5010-5016. Epub 2021 Apr 19.

Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.

Background: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition.

Methods: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated.

Results: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (β =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found.

Conclusions: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.
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http://dx.doi.org/10.21037/apm-20-2513DOI Listing
May 2021

Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050).

Lung Cancer 2021 04 23;154:176-185. Epub 2021 Feb 23.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address:

Objectives: To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial.

Materials And Methods: In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation). The primary endpoint was PFS by blinded independent review.

Results: Of 346 Asian patients, 170 were randomized to dacomitinib and 176 to gefitinib. The hazard ratio (HR) for PFS with dacomitinib versus gefitinib was 0.509 (95 % confidence interval [CI]: 0.391-0.662; 1-sided p < 0.0001; median 16.5 months [95 % CI: 12.9-18.4] vs. 9.3 months [95 % CI: 9.2-11.0]). HR for OS with dacomitinib versus gefitinib was 0.759 (95 % CI: 0.578-0.996; median 37.7 months [95 % CI: 30.2-44.7] vs. 29.1 months [95 % CI: 25.6-36.0]). The OS benefit was still maintained in those patients who had a stepwise dose reduction of dacomitinib (to 30 and 15 mg/day). The most common adverse events (AEs) were diarrhea (154 [90.6 %] patients), paronychia (110 [64.7 %]), dermatitis acneiform (96 [56.5 %]), and stomatitis (87 [51.2 %]) with dacomitinib, and diarrhea (100 [56.8 %]), alanine aminotransferase increased (81 [46.0 %]), and aspartate aminotransferase increased (75 [42.6 %]) with gefitinib. Treatment-related serious AEs were reported in 16 (9.4 %) and 8 (4.5 %) patients treated with dacomitinib and gefitinib, respectively.

Conclusion: First-line dacomitinib was associated with significant prolongation of PFS and improved OS compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC. The AE profiles of dacomitinib and gefitinib in Asian patients were consistent with the overall ARCHER 1050 population.
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http://dx.doi.org/10.1016/j.lungcan.2021.02.025DOI Listing
April 2021

A Synergistic Effect of Lp(a) and GRACE Score on Cardiovascular Risk in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Cohort Study From China.

Front Cardiovasc Med 2021 19;8:637366. Epub 2021 Feb 19.

Department of Cardiology, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Lipoprotein(a) [Lp(a)] has been thought as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The Global Registry of Acute Coronary Events (GRACE) score is used to predict the risk of death or death/non-fatal myocardial infarction in patients with acute coronary syndromes (ACS). It suggests that there may be a synergism between Lp(a) and the GRACE risk score on predicting cardiovascular events. Accordingly, this study aimed to test the hypothesis that Lp(a)-related cardiovascular risk could be significantly modulated by the GRACE risk score in patients with ACS undergoing percutaneous coronary intervention (PCI). Patients hospitalized with ACS undergoing PCI were enrolled and followed up for 18 months. The primary outcome was the composite of death, non-fatal myocardial infarction, non-fatal stroke, and unplanned repeat revascularization. A Cox proportional hazard regression model was used to determine the relationship between Lp(a) and cardiovascular events. A total of 6,309 patients were included (age: 60.1 ± 10.06 years, male: 75.2%, BMI: 26.2 ± 10.57 kg/m). A total of 310 (4.9%) cardiovascular events occurred. When the overall population was stratified by a GRACE score of 91 or less vs. more than 91 and by tertiles of Lp(a), higher Lp(a) was significantly associated with cardiovascular events only when the GRACE score was <91(tertile 2 vs. tertile 1: HR 1.31, 95% CI: 0.86-1.98, = 0.205; tertile 3 vs. tertile 1: HR 1.94, 95% CI: 1.32-2.84, = 0.001; = 0.002). However, no such significant correlation between cardiovascular events and Lp(a) emerged in the case of a GRACE score 91 or less, and there was a significant interaction for cardiovascular events between Lp(a) tertiles and dichotomized GRACE scores ( < 0.001). In ACS patients undergoing PCI, there was a synergistic effect between the GRACE risk score and on-statins Lp(a) on predicting cardiovascular events. This finding could help us more accurately identify patients who would benefit most from Lp(a)-lowering treatment.
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http://dx.doi.org/10.3389/fcvm.2021.637366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933013PMC
February 2021

Elevated Glycated Albumin in Serum Is Associated with Adverse Cardiac Outcomes in Patients with Acute Coronary Syndrome Who Underwent Revascularization Therapy.

J Atheroscler Thromb 2021 Feb 27. Epub 2021 Feb 27.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University.

Aims: The associations between increased glycated albumin (GA) in the serum and diabetic complications and mortality have been revealed in the general population. However, less is known regarding the prognostic value of GA in patients diagnosed with acute coronary syndrome (ACS).

Methods: In this study, all patients admitted for ACS who underwent a successful percutaneous coronary intervention (PCI) at our center from January 2018 to February 2019 were retrospectively examined. Clinical characteristics, laboratory results (e.g., serum GA levels), and procedural details were collected. The primary outcome included a composite of major adverse cardio-cerebral events (MACCE), such as death, myocardial infarction, stroke, and unplanned revascularization. The association between serum GA levels and clinical outcomes was tested in three multivariable models using Cox proportional hazard analysis. Subgroup analysis was performed in patients who were diagnosed with diabetes versus patients without diabetes.

Results: A total of 1,806 ACS patients (mean age of 59.4 years; 77.8% were men; 44.9% were diagnosed with diabetes) were enrolled in this study, where the majority exhibited unstable angina (81.6%) and showed preserved left ventricular systolic function. Patients in the high GA level group were commonly female and were more likely to have metabolic disorders and to exhibit severe CAD (all p<0.05). MACCE occurred in 126 patients (7.0%) during a mean follow-up time of 17.2 months. The cumulative risk of MACCE at the 18-month follow-up visit significantly increased in a stepwise fashion along with increased GA levels (log-rank p=0.018) in the serum. The association between serum GA levels and MACCE was further determined after adjusting traditional risk factors and hemoglobin A1c (HbA1c) (GA, per 1% increase: hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.06-1.13; GA, higher vs. lower tertial: HR 1.92, 95% CI 1.01-3.67). In a subgroup analysis, the prognostic role of serum GA only existed in diabetic patients, even when adjusting for traditional risk factors and HbA1c levels.

Conclusions: Elevated GA levels in the serum were associated with poor intermediate-term outcomes in low-risk ACS patients who underwent PCI, especially in patients with preexisting diabetes.
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http://dx.doi.org/10.5551/jat.61358DOI Listing
February 2021

Serum IL-6 as a vital predictor of severe lung cancer.

Ann Palliat Med 2021 Jan;10(1):202-209

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, China; Hunan Provincial Clinical Research Center for Respiratory Diseases, Changsha, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, Changsha, China. Email:

Background: Recent clinical studies have reported that some cytokines are associated with lung cancer prognosis and mortality. However, the relationship between cytokines and clinical outcomes in severe lung cancer patients was unclear. IL-6 as an important cytokine in inflammation, expression level in severe lung cancer patients was unknown.

Methods: A cohort of 55 severe lung cancer patients were enrolled retrospectively in this study. The clinical characteristics, including performance status (PS), therapeutic effect, and patients' adverse effects, were recorded. The association of cytokines and the concerned clinical outcomes were assessed by logistic regression analysis. The area under the curve (AUC) was assessed to evaluate the strength of prediction.

Results: The mean age of the patients was 59.8, and 42 patents were males. Increased IL-6 levels were associated with worse PS. Logistic regression analysis demonstrated that higher IL-6 was associated with an increased risk of progressive disease (PD) (OR =1.03, 95% CI: 1.0-1.06). The area under the ROC curve (AUC) of the model used for predicting PD was 0.821.

Conclusions: Increased IL-6 levels are correlated with worse PS and are an essential predictor for PD in severe lung cancer patients. Monitoring the IL-6 level may represent an essential strategy in improving the prognosis of patients with severe lung cancer.
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http://dx.doi.org/10.21037/apm-20-2229DOI Listing
January 2021

Usefulness of candidate mRNAs and miRNAs as biomarkers for mild cognitive impairment and Alzheimer's disease.

Int J Neurosci 2021 Mar 14:1-14. Epub 2021 Mar 14.

Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.

Objective: To explore potential molecular mechanisms and novel biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods: The mRNA expression datasets GSE63060 and GSE63061 and the miRNA expression dataset GSE120584 were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and miRNA (DEmiRs) were identified in the normal, MCI, and AD groups. Mfuzz clustering and weighted correlation network analyses (WGCNA) were conducted, followed by pathway and functional enrichment analyses and miRNA-mRNA network construction. Furthermore, phenotypic correlation analysis and experimental verification were performed on key DEGs and DEmiRs.

Results: In total, 3,000 intersected DEGs from GSE63060/GSE63061 and 817 DEmiRs from GSE120584 were obtained. Mfuzz and WGCNA analyses revealed 106 DEGs including ribosomal protein L11 () and 28 DEmiRs including miR-6764-5p. These DEGs and DEmiRs were mainly enriched in pathways like Ribosome. Moreover, 5 key DEGs including cytohesin 4 () and 6 crucial DEmiRs including miR-6734-3p were identified by miRNA-mRNA interaction network analysis. Phenotypic correlation analysis showed that and miR-6734-3p were correlated with patients' age. The results of quantitative polymerase chain reaction analysis confirmed that expression was significantly downregulated in the MCI and AD groups compared to that in the normal group, while the expression of , miR-6764-5p, and miR-6734-3p was remarkably upregulated in the MCI and AD groups.

Conclusions: miR-6764-5p might contribute to MCI and AD by targeting in the ribosome pathway. Therefore, miR-6734-3p and its target mRNA might be used as novel biomarkers for MCI and AD.
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http://dx.doi.org/10.1080/00207454.2021.1886098DOI Listing
March 2021

Perivascular Adipose Tissue as an Indication, Contributor to, and Therapeutic Target for Atherosclerosis.

Front Physiol 2020 18;11:615503. Epub 2020 Dec 18.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China.

Perivascular adipose tissue (PVAT) has been identified to have significant endocrine and paracrine functions, such as releasing bioactive adipokines, cytokines, and chemokines, rather than a non-physiological structural tissue. Considering the contiguity with the vascular wall, PVAT could play a crucial role in the pathogenic microenvironment of atherosclerosis. Growing clinical evidence has shown an association between PVAT and atherosclerosis. Moreover, based on computed tomography, the fat attenuation index of PVAT was verified as an indication of vulnerable atherosclerotic plaques. Under pathological conditions, such as obesity and diabetes, PVAT shows a proatherogenic phenotype by increasing the release of factors that induce endothelial dysfunction and inflammatory cell infiltration, thus contributing to atherosclerosis. Growing animal and human studies have investigated the mechanism of the above process, which has yet to be fully elucidated. Furthermore, traditional treatments for atherosclerosis have been proven to act on PVAT, and we found several studies focused on novel drugs that target PVAT for the prevention of atherosclerosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PVAT warrants further investigation.
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http://dx.doi.org/10.3389/fphys.2020.615503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775482PMC
December 2020

Later-Onset Hypertension Is Associated With Higher Risk of Dementia in Mild Cognitive Impairment.

Front Neurol 2020 26;11:557977. Epub 2020 Nov 26.

Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.

To investigate the correlation between hypertension development and the progression of mild cognitive impairment (MCI) to dementia in middle-aged and elderly people. A population-based longitudinal cognition survey of people aged 55+ was conducted. The hypertension onset age was estimated by self-reported information and medical insurance card records. To study the effect of later-onset hypertension on dementia, the incidence of dementia was compared between the two groups. Of 277 hypertensive MCI participants without dementia, 56 (20.22%) progressed to dementia (MCIp) over the 6-year follow-up. The proportion of MCIp participants in the old-age-onset hypertension group (≥65 years) was higher than that in the middle-age-onset hypertension group (27.0 vs. 15.4%, respectively; = 5.538, = 0.019). In the old-age-onset hypertension group, the proportion of MCIp without diabetes mellitus was higher than those with diabetes mellitus (24.7 vs. 12.6%, respectively; = 5.321, = 0.021) and those with increased pulse pressure was higher than those without increased pulse pressure (33.3 vs. 15.4%, respectively; = 3.902, = 0.048). However, the cox proportional hazard showed that older age was the only risk factor for MCIp (HR = 0.618, = 0.000). These results suggest that individuals with later-onset hypertension may have greater cognition decline, even with blood pressure maintained at 130/80 mmHg with antihypertensive management.
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http://dx.doi.org/10.3389/fneur.2020.557977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726443PMC
November 2020

Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078).

Lung Cancer 2021 02 24;152:7-14. Epub 2020 Nov 24.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, 106 Zhongshan Second Road, Guangzhou 510080, China. Electronic address:

Background: In the phase 3 CheckMate 078 study, nivolumab showed significant overall survival (OS) benefit and superior tolerability versus docetaxel in a predominantly Chinese patient population with non-small cell lung cancer (NSCLC). However, data on long-term outcomes with immunotherapy in Asian patients are limited. We report 2-year efficacy and safety data.

Methods: Patients with advanced/metastatic NSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks; n = 338) or docetaxel (75 mg/m every 3 weeks; n = 166) until progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was OS; secondary endpoints included progression-free survival, objective response rate, and safety.

Results: After 25.9 months minimum follow-up, 21 patients (6 %) remained on nivolumab versus 0 on docetaxel. Median OS was 11.9 months with nivolumab versus 9.5 months with docetaxel (HR: 0.75; 95 % CI: 0.61-0.93); 2-year OS rates were 28 % versus 18 %, respectively. Survival benefits were observed across a variety of predefined subgroups. At 2 years, 39 % and 0 % of responders had ongoing responses with nivolumab and docetaxel, respectively. Grade 3-4 treatment-related adverse events occurred in 12 % of patients with nivolumab versus 47 % with docetaxel, leading to discontinuation in 4 % and 5 % of patients, respectively. No new treatment-related deaths occurred.

Conclusion: At 2 years, nivolumab maintained a favorable safety profile and continued to demonstrate superior OS versus docetaxel in this predominantly Chinese patient population with previously treated NSCLC. These data are consistent with long-term outcomes from the global CheckMate 017/057 studies.
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http://dx.doi.org/10.1016/j.lungcan.2020.11.013DOI Listing
February 2021

Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study.

Int J Cancer 2021 05 9;148(9):2313-2320. Epub 2020 Dec 9.

State Key Laboratory of Translation Oncology, Chinese University of Hong Kong, Hong Kong, China.

In the global KEYNOTE-042 study (Clinicaltrials.gov, NCT02220894), pembrolizumab significantly improved overall survival (OS) vs chemotherapy in patients with previously untreated programmed death ligand 1 (PD-L1)-positive locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. We present results from patients in KEYNOTE-042 enrolled from China in the global or extension study (NCT03850444; protocol identical to global study). Patients were randomized 1:1 (stratified by ECOG performance status 0 vs 1, squamous vs nonsquamous histology and PD-L1 tumor proportion score [TPS] ≥50% vs 1%-49%) to 35 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) or investigator's choice of 4 to 6 cycles of carboplatin plus paclitaxel or pemetrexed Q3W with optional pemetrexed maintenance for nonsquamous tumors. Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20% or ≥1%. Two hundred sixty-two patients (pembrolizumab, n = 128; chemotherapy, n = 134) were enrolled from China. At data cutoff (February 21, 2020; median follow-up, 33.0 [range, 25.6-41.9] months), pembrolizumab was shown to improve OS vs chemotherapy in patients with PD-L1 TPS ≥50% (hazard ratio [95% CI], 0.63 [0.43-0.94]), TPS ≥20% (0.66 [0.47-0.92]) and TPS ≥1% (0.67 [0.50-0.89]). Grade 3 to 5 treatment-related adverse events occurred less frequently with pembrolizumab vs chemotherapy (19.5% vs 68.8%). In 22 patients who completed 35 cycles of pembrolizumab, objective response rate was 77.3% and median duration of response was 27.6 months. Consistent with the global KEYNOTE-042 study, pembrolizumab improved OS vs chemotherapy in this study of Chinese patients with locally advanced/metastatic NSCLC and PD-L1 TPS ≥1%, supporting first-line pembrolizumab monotherapy for PD-L1-positive advanced/metastatic NSCLC in China.
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http://dx.doi.org/10.1002/ijc.33399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048589PMC
May 2021

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases.

Transl Lung Cancer Res 2020 Oct;9(5):2016-2026

Department of Respiration, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases.

Methods: A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules.

Discussion: We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis.

Trial Registration: Clinicaltrials.gov NCT03651986.
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http://dx.doi.org/10.21037/tlcr-20-701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653103PMC
October 2020
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