Publications by authors named "Han Chen"

767 Publications

Anisotropic Shear-Sensitive Tactile Sensors with Programmable Elastomers for Robotic Manipulations.

ACS Appl Mater Interfaces 2021 Oct 19. Epub 2021 Oct 19.

Soft Intelligence Lab, State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

High-performance tactile sensors are urgently demanded in various intensive interactive scenarios, e.g., texture detection, robotic interaction with fragile objects, and motion direction recognition, where dynamic conditions are involved with complex tangential forces or vibrations. Although many microstructured/porous sensors can perceive tangential forces, their isotropic structures that lack programmability lead them to be incapable of sensing the direction of forces and restrain their tunability for complex situations, e.g., a wide sensing range for large forces and high sensitivity for gentle forces. Here, by tuning the programmable microstructures (microcolumns and microfilms) of an elastomeric active layer, we propose a simple principle to flexibly tune the shear sensitivity of an anisotropic porous sensor and bring a 10-fold distinction of anisotropy with a wide range of shear sensitivity (from 0.07 to 0.7 N). The fabricated tactile sensors can be used in various robotic manipulations resiliently, for instance, morphology and topology identification of curved surfaces, delicate interactive manipulations, and recognizing the relative motion of two contacting objects. Our work introduces a simple and effective strategy for tailoring flexible shear-sensitive sensors for diverse dexterous robotic manipulations during complex interactions.
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http://dx.doi.org/10.1021/acsami.1c12985DOI Listing
October 2021

Immediate Renal Denervation After Acute Myocardial Infarction Mitigates the Progression of Heart Failure via the Modulation of IL-33/ST2 Signaling.

Front Cardiovasc Med 2021 1;8:746934. Epub 2021 Oct 1.

Department of Cardiology, Zhongshan Hospital, Fudan University, Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Shanghai, China.

Previous studies have demonstrated the protective effects of renal denervation (RDN) in pre-existing heart failure, but the effects of immediate RDN after acute myocardial infarction (AMI) on subsequent cardiac remodeling have not been reported. This study aimed to investigate the cardioprotective effects of immediate RDN after AMI and its underlying mechanism. AMI was induced by intracoronary gelatin sponge embolization in 14 Shanghai white pigs that were randomized to undergo either renal angiography (AMI+sham group) or RDN (AMI+RDN group) after 1 h of hemodynamic monitoring. Cardiac function of the two groups was measured at baseline, 1 h post-AMI and at the 1 month follow-up (1M-FU) by transthoracic echocardiography (TTE). Plasma NT-proBNP, soluble ST2 (sST2), norepinephrine (NE), and renin-angiotensin-aldosterone system activity were detected simultaneously. The renal cortex was harvested for NE measurement after the 1M-FU, and the renal arteries were stained with tyrosine hydroxylase for the evaluation of sympathetic activity. Heart tissues in the non-ischemic areas were collected to assess histological and molecular left ventricular (LV) remodeling by pathological staining, RT-PCR, and western blotting. There was no difference in the hemodynamic stability or cardiac function between the two groups at baseline and 1 h post-AMI. Six pigs from each of the two groups completed the 1M-FU. TTE analysis revealed the improved cardiac function of immediate RDN in the AMI+RDN group and circulating NT-proBNP levels were lower than those in the AMI+sham group. Further analysis showed significantly less interstitial fibrosis in the remote non-ischemic myocardium after immediate RDN, together with decreased cardiomyocyte hypertrophy and inflammatory cell infiltration. sST2 levels in circulating and myocardial tissues of animals in the AMI+RDN group were significantly higher than those in the AMI+sham group, accompanied by corresponding alterations in IL-33/ST2 and downstream signaling. Immediate RDN can improve cardiac function and myocardial remodeling after AMI via modulation of IL-33/ST2 and downstream signaling.
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http://dx.doi.org/10.3389/fcvm.2021.746934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517399PMC
October 2021

Performance of Lactate and CO-Derived Parameters in Predicting Major Postoperative Complications After Cardiac Surgery With Cardiopulmonary Bypass: Protocol of a Diagnostic Accuracy Study.

Front Cardiovasc Med 2021 1;8:724713. Epub 2021 Oct 1.

Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.

CO-derived parameters are increasingly used to identify either low-flow status or anaerobic metabolism in shock resuscitation. However, the performance of CO-derived parameters in cardiac surgical patients is poorly understood. This study aims to compare the performance of lactate and CO-derived parameters in predicting major postoperative complications after cardiac surgery with cardiopulmonary bypass. This is a prospective, single-center, diagnostic accuracy study. All patients who receive elective cardiac surgery involving cardiopulmonary bypass will be screened for study eligibility. Blood samples will be taken for the calculation of CO-derived parameters, including the venous-arterial difference in CO partial pressure (PCO gap), venous-arterial difference in CO content to arterial-venous O content ratio (Cv-aCO/Ca-vO), and venous-arterial difference in CO partial pressure to arterial-venous O content ratio (Pv-aCO/Ca-vO) at ICU admission, and 3, 6, and 12 h later. Baseline, perioperative data will be collected daily for 7 days; patients will be followed up for 28 days to collect outcome data. The primary endpoint is the occurrence of major postoperative complications. Receiver-operating characteristics (ROC) curve analysis will be carried out to assess the predictive performance of lactate and CO-derived parameters. The performance of the ROC curves will be compared. The performance of lactate and CO-derived parameters in predicting major postoperative complications will be investigated in the non-sepsis population, which has not been extensively investigated. Our study will compare the two surrogates of respiratory quotient directly, which is an important strength. ChiCTR, ChiCTR2000029365. Registered January 26th, 2020, http://www.chictr.org.cn/showproj.aspx?proj=48744.
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http://dx.doi.org/10.3389/fcvm.2021.724713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517114PMC
October 2021

A Food Safety Education Needs Assessment for Small-Scale Produce Growers Interested in Value-Added Food Production.

J Food Prot 2021 Oct 14. Epub 2021 Oct 14.

Purdue University Assistant Professor Food Science 745 Agriculture Mall Dr. UNITED STATES West Lafayette In 47907 +15305742267.

Production of value-added foods is of growing interest to small-scale produce growers. However, previous studies reported that they lack sufficient food safety awareness and have limited knowledge of applicable food safety regulations. Targeted food safety education can help to address these challenges. This study used focus groups and a combination of web-based and printed surveys to evaluate growers' attitudes toward and knowledge of value-added business and to assess their food safety education needs. A total of 136 Indiana produce growers participated in the study, including 38 focus group participants and 98 survey participants. Overall, growers were aware of the importance of food safety, with 78% of the survey participants agreeing strongly that food safety was a top priority in value-added businesses. Most survey participants (82%) self-reported being knowledgeable about food safety. Most were confident in their ability to run a successful value-added business. The top two barriers that hindered growers from learning about food safety were time limitations and an overwhelming amount of information. Growers preferred to receive additional educational materials on selling non-home-based vendor products, communication strategies with regulators and inspectors, and marketing strategies; they trusted the information from extension educators and university extension publications the most. This study guides the development of future food safety education programs for small-scale growers who are interested in establishing a value-added business.
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http://dx.doi.org/10.4315/JFP-21-193DOI Listing
October 2021

Specific interaction of an RNA-binding protein with the 3'-UTR of its target mRNA is critical to oomycete sexual reproduction.

PLoS Pathog 2021 Oct 14;17(10):e1010001. Epub 2021 Oct 14.

Department of Plant Pathology, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Sexual reproduction is an essential stage of the oomycete life cycle. However, the functions of critical regulators in this biological process remain unclear due to a lack of genome editing technologies and functional genomic studies in oomycetes. The notorious oomycete pathogen Pythium ultimum is responsible for a variety of diseases in a broad range of plant species. In this study, we revealed the mechanism through which PuM90, a stage-specific Puf family RNA-binding protein, regulates oospore formation in P. ultimum. We developed the first CRISPR/Cas9 system-mediated gene knockout and in situ complementation methods for Pythium. PuM90-knockout mutants were significantly defective in oospore formation, with empty oogonia or oospores larger in size with thinner oospore walls compared with the wild type. A tripartite recognition motif (TRM) in the Puf domain of PuM90 could specifically bind to a UGUACAUA motif in the mRNA 3' untranslated region (UTR) of PuFLP, which encodes a flavodoxin-like protein, and thereby repress PuFLP mRNA level to facilitate oospore formation. Phenotypes similar to PuM90-knockout mutants were observed with overexpression of PuFLP, mutation of key amino acids in the TRM of PuM90, or mutation of the 3'-UTR binding site in PuFLP. The results demonstrated that a specific interaction of the RNA-binding protein PuM90 with the 3'-UTR of PuFLP mRNA at the post-transcriptional regulation level is critical for the sexual reproduction of P. ultimum.
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http://dx.doi.org/10.1371/journal.ppat.1010001DOI Listing
October 2021

Learning delay dynamics for multivariate stochastic processes, with application to the prediction of the growth rate of COVID-19 cases in the United States.

J Math Anal Appl 2021 Sep 28:125677. Epub 2021 Sep 28.

Department of Statistics, University of California, Davis, United States of America.

Delay differential equations form the underpinning of many complex dynamical systems. The forward problem of solving random differential equations with delay has received increasing attention in recent years. Motivated by the challenge to predict the COVID-19 caseload trajectories for individual states in the U.S., we target here the inverse problem. Given a sample of observed random trajectories obeying an unknown random differential equation model with delay, we use a functional data analysis framework to learn the model parameters that govern the underlying dynamics from the data. We show the existence and uniqueness of the analytical solutions of the population delay random differential equation model when one has discrete time delays in the functional concurrent regression model and also for a second scenario where one has a delay continuum or distributed delay. The latter involves a functional linear regression model with history index. The derivative of the process of interest is modeled using the process itself as predictor and also other functional predictors with predictor-specific delayed impacts. This dynamics learning approach is shown to be well suited to model the growth rate of COVID-19 for the states that are part of the U.S., by pooling information from the individual states, using the case process and concurrently observed economic and mobility data as predictors.
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http://dx.doi.org/10.1016/j.jmaa.2021.125677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494512PMC
September 2021

A nomogram for predicting lymph node metastasis in superficial esophageal squamous cell carcinoma.

J Biomed Res 2021 Aug;35(5):361-370

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Superficial esophageal squamous cell carcinoma (SESCC) is defined as carcinoma with mucosal or submucosal invasion, regardless of regional lymph node metastasis (LNM). The lymph node status is not only a key factor to determine the training strategy, but also the most important prognostic factor in esophageal cancer. In this study, we establish a clinical nomogram for predicting LNM in patients with SESCC. A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018. A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation. Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed (concordance index [C-index], 0.860; 95% confidence interval [CI], 0.825-0.894) through internal validation. The external validation cohort presented good discrimination (C-index, 0.916; 95% CI, 0.860-0.971). This model may facilitate the prediction of LNM in patients with SESCCs.
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http://dx.doi.org/10.7555/JBR.35.20210034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502689PMC
August 2021

The Mechanism of Piezocatalysis: Energy Band Theory or Screening Charge Effect?

Angew Chem Int Ed Engl 2021 Oct 6. Epub 2021 Oct 6.

Curtin University, Chem Eng, 208 Kent St, 6155, Perth, AUSTRALIA.

Piezocatalysis, a new-emerging catalysis technology relying on catalyst's piezopotential and piezoelectric property, is attracting unprecedented research enthusiasm for applications in energy conversion, organic synthesis, and environmental remediation. Despite the rapid development in the past three years, the mechanism for piezocatalysis is still in debate. A fundamental understanding of the working principles should be enhanced to further advance this technology for future piezocatalysts design and system optimization. In this article, we review the two popular theories to explain the observed piezocatalysis in terms of the energy band theory and the screening charge effect. A comprehensive discussion and clarification of the difference, relevance, evidence and contradiction of the two mechanisms is provided. Finally, the challenges and perspectives of the future mechanic study are put forward. Hopefully, this review can help readers to gain a better understanding and to start quickly in applying piezocatalysis to their own research.
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http://dx.doi.org/10.1002/anie.202110429DOI Listing
October 2021

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Cell Rep Med 2021 Oct 28;2(10):100421. Epub 2021 Sep 28.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA, USA.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.
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http://dx.doi.org/10.1016/j.xcrm.2021.100421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479532PMC
October 2021

Ophthalmic services in Shanghai 2017: a cataract-centric city-wide government survey.

BMC Health Serv Res 2021 Oct 2;21(1):1043. Epub 2021 Oct 2.

Eye Institute of Eye and Ear, Nose, and Throat Hospital of Fudan University; Key Laboratory of Myopia, Ministry of Health; Key Laboratory of Visual Impairment and Restoration of Shanghai, Fudan University; Key NHC key Laboratory of Myopia, Fudan University; Chinese Academy of Medical Sciences, 83 Fenyang Road, Shanghai, 200031, China.

Background: Demand for eye care has increased in recent decades in China due to rapid socioeconomic development and demographic shift. Knowledge of output and productivity of ophthalmic services would allow policymakers to optimize resource allocation, and is therefore essential. This study sought to map the landscape of ophthalmic services available in Shanghai, China.

Methods: In 2018, a government-led survey was conducted of all 86 tertiary/secondary hospitals and five major private hospitals providing eye care in Shanghai in the form of electronic questionnaire, which encompassed ophthalmic services (outpatient and emergency room [ER] visit, inpatient admissions, and surgical volume) and service productivity in terms of annual outpatient and ER visits per doctor, inpatient admissions per bed, and surgical volume per doctor. Comparisons were made among different levels of hospitals with categorical variables tested by Chi-square analysis.

Results: The response rate was 85.7%. The Eye and Ear, Nose, and Throat (EENT) Hospital was the largest tertiary specialty hospital, and alone contributed to the highest 21.0% of annual ophthalmic outpatient and ER visits (visits per doctor: 5460), compared with other 26 tertiary hospitals, 46 secondary hospitals and five private hospitals (visits per doctor: 3683, 4651 and 1876). The annual inpatient admission was 20,103, 56,992, 14,090, and 52,047 for the EENT Hospital, all the other tertiary hospitals, secondary hospitals and five private hospitals, respectively. Turnover rates were highest for the EENT Hospital and private hospitals. The average surgical volume at the EENT Hospital was 72,666, exceeding that of private (15,874.8) and other tertiary hospitals (3366.7). The EENT Hospital and private hospitals performed 16,982 (14.2%) and 55,538 (46.6%) of all cataract surgeries. Proportions of both complicated cataractous cases and complicated cataract surgeries at the EENT Hospital was the highest, followed by other tertiary and secondary/private hospitals (P < 0.0001).

Conclusions: In Shanghai, public providers dominate ophthalmic services especially for complicated cases, with almost one fifth of services provided by the EENT Hospital alone, while private sectors, though not large in number, still effectively help meet large proportions of eye care demand. Optimization of hierarchical medical system is warranted to improve the efficiency and standardization of ophthalmic services.
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http://dx.doi.org/10.1186/s12913-021-07048-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487503PMC
October 2021

Elevated risk of haloacetonitrile formation during post-chlorination when applying sulfite/UV advanced reduction technology to eliminate bromate.

Sci Total Environ 2021 Sep 28;806(Pt 2):150612. Epub 2021 Sep 28.

Ministry of Education Key Laboratory of Integrated Regulation and Resource Development on Shallow Lakes, Hohai University, Nanjing 210098, PR China; College of Environment, Hohai University, Nanjing 210098, PR China.

The formation of haloacetonitriles (HANs) during chlorination after sulfite/ultraviolet (UV) treatment of bromate (BrO) in the presence of amino acids (AAs) was investigated. During sulfite/UV treatment, the primary species hydrated electrons (e) and hydrogen atom radicals (H) dominated the reduction of BrO to bromide (Br), whereas the sulfite anion radicals (SO) and H degraded AAs to produce the intermediates HN=C(CH)-COOH, CH-CH=NH, and CH-C≡N via α‑hydrogen abstraction and NH-hydrogen abstraction mechanisms. During post-chlorination, Br was converted to HBrO/BrO-, and the HN=C(CH)-COOH, CH-CH=NH, and CH-C≡N groups featured higher bromine utilization factor (BUF) and chlorine utilization factor (CUF) values than AAs, enhancing the formation of dibromoacetonitrile (DBAN) and dichloroacetonitrile (DCAN). The energetic feasibility of the transformation pathway, that is, HN=C(CH)-COOH, CH-CH=NH, and CH-C ≡ N formation via hydrogen abstraction by SO and H and their further conversion to HANs, was proved by density functional theory calculations, which showed stepwise negative Gibbs free energy changes (ΔG < 0). The effects of pH and water matrices (e.g., HCO, Cl, Fe, and natural organic matter) were comprehensively evaluated. Although 72% of BrO was removed by sulfite/UV treatment in the presence of AAs, the cytotoxicity index (CTI) and genotoxicity index (GTI) during post-chlorination increased by 213% and 125%, respectively, due to the formation of 24 CXR-type disinfection by-products (DBPs), especially brominated DBPs. Accordingly, more attention should be given to the formation of brominated DBPs during post-chlorination when using sulfite/UV processes to remove BrO in the presence of AAs. As a solution, using monochloramine instead of chlorine as a disinfectant after the sulfite/UV process could significantly lower the CTI and GTI values by alleviating the formation of brominated DBPs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150612DOI Listing
September 2021

Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function.

Sci Rep 2021 Sep 29;11(1):19365. Epub 2021 Sep 29.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.
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http://dx.doi.org/10.1038/s41598-021-98120-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481467PMC
September 2021

Development and clinical deployment of a smartphone-based visual field deep learning system for glaucoma detection.

NPJ Digit Med 2020 Sep 22;3(1):123. Epub 2020 Sep 22.

Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, People's Republic of China.

By 2040, ~100 million people will have glaucoma. To date, there are a lack of high-efficiency glaucoma diagnostic tools based on visual fields (VFs). Herein, we develop and evaluate the performance of 'iGlaucoma', a smartphone application-based deep learning system (DLS) in detecting glaucomatous VF changes. A total of 1,614,808 data points of 10,784 VFs (5542 patients) from seven centers in China were included in this study, divided over two phases. In Phase I, 1,581,060 data points from 10,135 VFs of 5105 patients were included to train (8424 VFs), validate (598 VFs) and test (3 independent test sets-200, 406, 507 samples) the diagnostic performance of the DLS. In Phase II, using the same DLS, iGlaucoma cloud-based application further tested on 33,748 data points from 649 VFs of 437 patients from three glaucoma clinics. With reference to three experienced expert glaucomatologists, the diagnostic performance (area under curve [AUC], sensitivity and specificity) of the DLS and six ophthalmologists were evaluated in detecting glaucoma. In Phase I, the DLS outperformed all six ophthalmologists in the three test sets (AUC of 0.834-0.877, with a sensitivity of 0.831-0.922 and a specificity of 0.676-0.709). In Phase II, iGlaucoma had 0.99 accuracy in recognizing different patterns in pattern deviation probability plots region, with corresponding AUC, sensitivity and specificity of 0.966 (0.953-0.979), 0.954 (0.930-0.977), and 0.873 (0.838-0.908), respectively. The 'iGlaucoma' is a clinically effective glaucoma diagnostic tool to detect glaucoma from humphrey VFs, although the target population will need to be carefully identified with glaucoma expertise input.
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http://dx.doi.org/10.1038/s41746-020-00329-9DOI Listing
September 2020

The effect of group cognitive behavior therapy on Chinese patients with anorexia nervosa: an open label trial.

J Eat Disord 2021 Sep 15;9(1):114. Epub 2021 Sep 15.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wanping Road, Shanghai, China.

Background: The high cost of treatment for anorexia nervosa (AN) and lack of trained specialists have resulted in limited accessibility of effective treatment to patients with AN, which is particularly problematic in China. To increase the accessibility of evidence-based treatment and reduce the cost of treatment, this study aimed to explore the feasibility and efficacy of group cognitive behavior therapy (G-CBT) adapted from enhanced cognitive behavior therapy for eating disorders (CBT-E) in Chinese AN patients.

Method: A total of 78 patients with AN were assigned to G-CBT or individual outpatient treatment (IOT) and received three months of treatment for AN in each condition. Measures of eating pathology, depression and anxiety were administrated to both intervention groups at three time points: baseline, one month of treatment, and end of treatment; results were compared between groups and over time.

Results: There were 70 participants included in the final analysis. Both G-CBT and IOT groups showed significant improvement in eating pathology and associated psychopathology (ps < .001) over the course of treatment, but no significant difference in symptom improvement was found between the two groups (ps > .05). G-CBT resulted in additional significant improvement in ED psychopathology over the last two months of treatment, and its overall therapeutic effect was influenced by baseline weight and early symptom improvement.

Conclusion: Preliminary findings from this open label trial suggest that G-CBT adapted from CBT-E is feasible in an outpatient setting and as effective as IOT in facilitating weight regain and reducing psychopathology in Chinese AN patients with little evidence for the superiority of either intervention.

Trial Registration: The current study was registered at clinical trials.gov on September 23, 2018 (registration number NCT03684239). People with anorexia nervosa (AN) are known to be unmotivated for treatment and prone to relapse. Recovery from AN often needs intensive, long-term treatment from a specialized multidisciplinary team, which is not accessible for most people in China. Given the increasing incidence of AN and lack of eating disorder (ED) specialists in China, it is important to develop short-term cost-effective treatments for AN. In this study, we explored the feasibility and efficacy of group cognitive behavior therapy (G-CBT) adapted from enhanced cognitive behavior therapy (CBT-E) for people with AN from China. We found that G-CBT was as effective as individual outpatient treatment (IOT) typically provided to AN patients at the research site in facilitating weight regain, improving eating behaviors, and reducing ED and other symptoms. We also found that patients receiving G-CBT made more improvements in cognitive symptoms of the ED, which might help maintain treatment gains and prevent relapse in the long run. This potential long-term advantage of G-CBT needs to be verified in long-term follow-up.
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http://dx.doi.org/10.1186/s40337-021-00469-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444542PMC
September 2021

The divergent response of vegetation phenology to urbanization: A case study of Beijing city, China.

Sci Total Environ 2021 Sep 2;803:150079. Epub 2021 Sep 2.

College of Land Science and Technology, China Agricultural University, Beijing 100083, China.

Characterizing the relationship between vegetation phenology and urbanization indicators is essential to understand the impacts of human activities on urban ecosystems. In this study, we explored the response of vegetation phenology to urbanization in Beijing (China) during 2001-2018, using impervious surface area (ISA) and the information of urban-rural gradients (i.e., concentric rings from the urban core to surrounding rural areas) as the urbanization indicators. We found the change rates of vegetation phenology in urban areas are 1.3 and 1.1 days per year for start of season (SOS) and end of season (EOS), respectively, about three times faster than that in forest. Moreover, we found a divergent response of SOS with the increase of ISA, which differs from previous results with advanced SOS in the urban environment than surrounding rural areas. This might be attributed to the mixed land cover types and the thermal environment caused by the urban heat island in the urban environment. Similarly, a divergent pattern of phenological indicators along the urban-rural gradient shows a non-linear response of vegetation phenology to urbanization. These findings provide new insights into the complicated interactions between vegetation phenology and urban environments. High-resolution weather data are required to support process-based vegetation phenology models in the future, particularly under different global urbanization and climate change scenarios.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150079DOI Listing
September 2021

Death Pathways of Cancer Cells Modulated by Surface Molecule Density on Gold Nanorods.

Adv Sci (Weinh) 2021 Sep 15:e2102666. Epub 2021 Sep 15.

Department of Nanomedicine & International Joint Cancer Institute, Naval Medical University, Shanghai, 200433, China.

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρ (N /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρ mainly induce apoptosis, while with large ρ they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρ due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρ greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.
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http://dx.doi.org/10.1002/advs.202102666DOI Listing
September 2021

Prognostic Analysis of Diagnostic Ureteroscopic Biopsy for Intravesical Recurrence of Upper Urinary Tract Urothelial Carcinoma.

Urol Int 2021 Sep 7:1-9. Epub 2021 Sep 7.

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Objective: The aim of this study was to investigate whether diagnostic ureteroscopy (URS) biopsy is unfavourable for bladder tumour recurrence in upper urinary tract urothelial carcinoma (UTUC).

Materials And Methods: We performed a retrospective analysis of 195 patients diagnosed with UTUC, who were divided into a diagnostic URS group (URS+) and a nondiagnostic URS group (URS-) according to whether diagnostic ureteroscopic biopsy was performed. A Cox regression model was used to analyse the risk factors for intravesical recurrence (IVR)-free survival (IRFS) and overall survival (OS) in UTUC after radical nephroureterectomy (RNU). Kaplan-Meier analysis was used to estimate the influence of factors on the incidence of IVR and the cumulative survival rate of UTUC.

Results: Patients with a maximum tumour diameter of less than 3.1 cm, low-stage tumours, and ureteral tumours were more likely to undergo diagnostic URS before radical surgery. Multivariate Cox regression analysis showed that tumour pathological stage and diagnostic ureteroscopic biopsy can be used as predictors of IVR after RNU (p = 0.019, 0.033). Kaplan-Meier survival analysis found that diagnostic ureteroscopic biopsy was a high-risk factor for IRFS (p = 0.034). Subcomponent analysis showed that pTa/Tis/T1, pT2, pT3/pT4 stage, and diagnostic ureteroscopic biopsy with pTa/Tis/T1 stage were unfavourable for IVR (p = 0.047).

Conclusion: Diagnostic ureteroscopic biopsy before RNU should be carefully selected for patients with atypical preoperative UTUC. We believe that intravesical chemotherapy drug perfusion can be used after surgery to prevent IVR if biopsy is unavoidable, but this still requires further prospective studies.
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http://dx.doi.org/10.1159/000517789DOI Listing
September 2021

Oxidative Stress-Induced Ferroptosis in Cardiovascular Diseases and Epigenetic Mechanisms.

Front Cell Dev Biol 2021 19;9:685775. Epub 2021 Aug 19.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The recently discovered ferroptosis is a new kind of iron-regulated cell death that differs from apoptosis and necrosis. Ferroptosis can be induced by an oxidative stress response, a crucial pathological process implicated in cardiovascular diseases (CVDs). Accordingly, mounting evidence shows that oxidative stress-induced ferroptosis plays a pivotal role in angio-cardiopathy. To date, the inhibitors and activators of ferroptosis, as well as the many involved signaling pathways, have been widely explored. Among which, epigenetic regulators, molecules that modify the package of DNA without altering the genome, emerge as a highly targeted, effective option to modify the signaling pathway of ferroptosis and oxidative stress, representing a novel and promising therapeutic potential target for CVDs. In this review, we will briefly summarize the mechanisms of ferroptosis, as well as the role that ferroptosis plays in various CVDs. We will also expound the epigenetic regulators of oxidative stress-induced ferroptosis, and the promise that these molecules hold for treating the intractable CVDs.
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http://dx.doi.org/10.3389/fcell.2021.685775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416916PMC
August 2021

NLGN3 Upregulates Expression of ADAM10 to Promote the Cleavage of NLGN3 Activating the LYN Pathway in Human Gliomas.

Front Cell Dev Biol 2021 16;9:662763. Epub 2021 Aug 16.

Institute of Basic Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

The neuron derived synaptic adhesion molecular neuroligin-3 (NLGN3) plays an important role in glioma growth. While the role of autocrine NLGN3 in glioma has not been well-studied. The expression of NLGN3 in glioma was detected using immunohistochemistry. We further explored its function and regulatory mechanism in U251 and U87 cells with high expression of NLGN3. Knockdown of endogenous NLGN3 significantly reduced the proliferation, migration, and invasion of glioma cells and down-regulated the activity of the PI3K-AKT, ERK1/2, and LYN signaling pathways. In comparison, overexpression of NLGN3 yielded opposite results. Our results further demonstrate that LYN functions as a feedback mechanism to promote NLGN3 cleavage. This feedback regulation was achieved by upregulating the ADAM10 sheddase responsible for NLGN3 cleavage. Inhibition of ADAM10 suppressed the proliferation, migration, and invasion of glioma cells; oppositely, the expression of ADAM10 was correlated with a higher likelihood of lower grade glioma (LGG) in the brain. Our study demonstrates that glioma-derived NLGN3 promotes glioma progression by upregulating activity of LYN and ADAM10, which in turn promote NLGN3 cleavage to form a positive feedback loop. This pathway may open a potential therapeutic window for the treatment of human glioma.
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http://dx.doi.org/10.3389/fcell.2021.662763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415229PMC
August 2021

Comparison of endoscopic injection of botulinum toxin and steroids immediately after endoscopic submucosal dissection to prevent esophageal stricture: a prospective cohort study.

J Cancer 2021 2;12(19):5789-5796. Epub 2021 Aug 2.

Department of Gastroenterology, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Widespread endoscopic submucosal dissection (ESD) in early esophageal cancer patients is closely associated with esophageal stricture, which dramatically reduces patients' quality of life and increases huge medical burdens. Endoscopic injection of steroid was proved as a protective method for post-ESD strictures. Other materials such as botulinum toxin type A (BTX-A) may be potential candidates. We conducted this prospective cohort study to compare the efficacy and feasibility of endoscopic injection of BTX-A and triamcinolone acetonide (TA) for the prevention of esophageal stricture. Seventy-eight patients with esophageal mucosal defects of more than two thirds of the circumference were successively enrolled and divided into 3 groups: BTX-A group (group A, n=26), TA group (group B, n=16) and control group (group C, n=36). Patients in group A were immediately injected with BTX-A after ESD, in group B were immediately injected with TA and in group C received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 6 and 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in all groups received bougie dilation. All patients were followed up for one year. The proportion of patients developing stricture in BTX-A group was 30.00% (intention to treat analysis, 9/30) and 26.92% (per protocol analysis, 7/26), in TA group was 40.90% (intention to treat analysis, 9/22) and 43.75% (per protocol analysis, 7/16), and in control group was 84.21% (intention to treat analysis, 32/38) and 83.33% (per protocol analysis, 30/36) (p<0.001). When further comparing between each of the two groups, the incidence of esophageal stricture was lower in BTX-A group than that in control group (p<0.001), and lower in TA group than that in control group (p=0.004). Furthermore, in entire circumference mucosal defect subgroup, the esophageal stricture was significantly lower in BTX-A group than that in TA group (33.3% vs 100%, p=0.0454). Endoscopic injection of BTX-A and TA were effective in preventing post-ESD esophageal strictures and BTX-A injection was particularly effective in entire circumference mucosal defect patients. Multi-centered, randomized prospective study with larger sample size should be conducted. (Clinical trial registration number: ChiCTR2100042970, registered 1 February 2021, retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx).
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http://dx.doi.org/10.7150/jca.60720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408129PMC
August 2021

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.

Genome Med 2021 Aug 26;13(1):136. Epub 2021 Aug 26.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.

Background: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.

Methods: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation < 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap.

Results: We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways.

Conclusions: We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.
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http://dx.doi.org/10.1186/s13073-021-00917-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394596PMC
August 2021

Dealkenylative Ni-Catalyzed Cross-Coupling Enabled by Tetrazine and Photoexcitation.

J Am Chem Soc 2021 Sep 26;143(35):14046-14052. Epub 2021 Aug 26.

Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education and Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

A new and general method to functionalize the C(sp)-C(sp) bond of alkyl and alkene linkages has been developed, leading to the dealkenylative generation of carbon-centered radicals that can be intercepted to undergo Ni-catalyzed C(sp)-C(sp) cross-coupling. This one-pot protocol leverages the easily procured alkene feedstocks for organic synthesis with excellent functional group compatibility without the need for a photoredox catalyst.
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http://dx.doi.org/10.1021/jacs.1c05092DOI Listing
September 2021

Curcumenol mitigates chondrocyte inflammation by inhibiting the NF‑κB and MAPK pathways, and ameliorates DMM‑induced OA in mice.

Int J Mol Med 2021 10 26;48(4). Epub 2021 Aug 26.

Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China.

At present, an increasing number of individuals are affected by osteoarthritis (OA), resulting in a heavy socioeconomic burden. OA in knee joints is caused by the release of inflammatory cytokines and subsequent biomechanical and structural deterioration. To determine its anti‑inflammatory function, the current study investigated the use of the plant‑derived medicine, curcumenol, in OA treatment. Curcumenol was not cytotoxic to ATDC5 chondrocytes and primary chondrocytes, as determined using a cell viability test. When these cells were treated with TNF‑α and IL‑1β to induce inflammation, curcumenol treatment inhibited the progression of inflammation by inactivating the NF‑κB and MAPK signaling pathways, as well as decreasing the expression levels of MMP3 (as indicated by reverse transcription‑quantitative PCR and western blotting). Moreover, to analyze metabolic and catabolic status in high‑density and pellet culture, catalytic changes and the degradation of the extracellular matrix induced by TNF‑α and IL‑1β, were evaluated by alcian blue staining. These catalytic deteriorations were ameliorated by curcumenol. Using curcumenol in disease management, the mechanical and metabolic disruption of cartilage caused in the destabilization of medial meniscus (DMM) model was prevented . Thus, curcumenol mitigated inflammation in ATDC5 chondrocytes and primary mice chondrocytes, and also ameliorated OA in a DMM‑induced mouse model.
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http://dx.doi.org/10.3892/ijmm.2021.5025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416138PMC
October 2021

Estimation of total mediation effect for high-dimensional omics mediators.

BMC Bioinformatics 2021 Aug 23;22(1):414. Epub 2021 Aug 23.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.

Background: Environmental exposures can regulate intermediate molecular phenotypes, such as gene expression, by different mechanisms and thereby lead to various health outcomes. It is of significant scientific interest to unravel the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposure and traits. Mediation analysis is an important tool for investigating such relationships. However, it has mainly focused on low-dimensional settings, and there is a lack of a good measure of the total mediation effect. Here, we extend an R-squared (R[Formula: see text]) effect size measure, originally proposed in the single-mediator setting, to the moderate- and high-dimensional mediator settings in the mixed model framework.

Results: Based on extensive simulations, we compare our measure and estimation procedure with several frequently used mediation measures, including product, proportion, and ratio measures. Our R[Formula: see text]-based second-moment measure has small bias and variance under the correctly specified model. To mitigate potential bias induced by non-mediators, we examine two variable selection procedures, i.e., iterative sure independence screening and false discovery rate control, to exclude the non-mediators. We establish the consistency of the proposed estimation procedures and introduce a resampling-based confidence interval. By applying the proposed estimation procedure, we found that 38% of the age-related variations in systolic blood pressure can be explained by gene expression profiles in the Framingham Heart Study of 1711 individuals. An R package "RsqMed" is available on CRAN.

Conclusion: R-squared (R[Formula: see text]) is an effective and efficient measure for total mediation effect especially under high-dimensional setting.
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http://dx.doi.org/10.1186/s12859-021-04322-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381496PMC
August 2021

Global patterns of leaf construction traits and their covariation along climate and soil environmental gradients.

New Phytol 2021 Nov 8;232(4):1648-1660. Epub 2021 Sep 8.

Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Leaf functional traits and their covariation underlie plant ecological adaptations along environmental gradients, but there is limited information on the global covariation patterns of key leaf construction traits. To explore how leaf construction traits co-vary across diverse climate and soil environmental conditions, we compiled a global dataset including cell wall mass per unit leaf mass (CW ), leaf carbon (C) and calcium (Ca) concentrations, and specific leaf area (SLA) for 2348 angiosperm species from 340 sites world-wide. Our results demonstrated negative correlations between leaf C and Ca concentrations and between leaf C and SLA across diverse nongraminoid angiosperms. Leaf C concentration increased with increasing mean annual temperature (MAT) and mean annual precipitation (MAP) and with decreasing soil pH and calcium carbonate (CaCO ) concentration, whereas leaf Ca concentration and SLA exhibited the opposite responses to these environmental variables. The covariations of leaf Ca-C and of leaf SLA-C were stronger in habitats with lower MAT and MAP, and/or higher soil CaCO content. This global-scale analysis demonstrates that the leaf C and Ca concentrations and SLA together govern the C and biomass investment strategies in leaves of nongraminoids. We conclude that environmental conditions strongly shape leaf construction traits and their covariation patterns.
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http://dx.doi.org/10.1111/nph.17686DOI Listing
November 2021

[Association between early central venous pressure measurement and mortality in patients with sepsis: a data analysis of MIMIC-III database].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jul;33(7):786-791

Department of Critical Care Medicine, Provincial Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian, China. Corresponding author: Yu Rongguo, Email:

Objective: To investigate the association between early central venous pressure (CVP) measurement and mortality in patients with sepsis.

Methods: The adult patients with sepsis were identified from the health data of Medical Information Mart for Intensive Care-III v1.4 (MIMIC-III v1.4). Data of all adult patients with sepsis were collected, including gender, age, comorbidities, length of survival, total length of hospital stay and intensive care unit (ICU) stay, sequential organ failure assessment (SOFA) score, vital signs, laboratory test results on the first day, vasoactive agents usage, fluid input, urine output and fluid balance on the first day, need for renal replacement therapy and mechanical ventilation, diagnosis of sepsis, and the time and value of the first CVP measurement in the ICU. Patients were divided into early measurement and control groups based on whether or not they had a CVP measurement within the first 6 hours of ICU stay. According to the time of the first CVP measurement, the patients were subdivided into four subgroups: ≤ 3 hours, 4-6 hours, 7-12 hours and no measurement within 12 hours. The primary endpoint was 28-day mortality. The relationship between initial CVP and mortality was analyzed by Lowess smoothing method. Kaplan-Meier survival analysis and Log-Rank test were performed for univariate analysis. Cox regression analysis was performed for multivariate analysis to estimate the relationship between timeliness of CVP measurement and mortality.

Results: A total of 4 733 sepsis patients were enrolled, 1 673 of whom had CVP measured within 6 hours of admission to the ICU, and the other 3 060 patients served as the control group. There were no differences in demographic characteristics and underlying diseases between the two groups, except that the early CVP measurement group had less underlying renal failure compared with control group. The early CVP measurement group had higher lactic acid (Lac) levels and SOFA scores, indicating worse severity of disease as compared with control group. The 28-day mortality in the early CVP measurement group was significantly lower than that in the control group (34.2% vs. 40.7%, P < 0.01). The early CVP measurement group had shorter length of total hospitalization and longer length of ICU stay, higher rate of mechanical ventilation and vasoactive agents dependent, and more fluid input and fluid balanced in the first day of ICU stay compared with control group. Lowess smoothing analysis showed that a "U"-shaped relationship between initial CVP and mortality was identified, suggesting that too high or too low initial CVP was associated with worse survival. Kaplan-Meier survival analysis showed that compared with the patients without early CVP measurement within 12 hours, the cumulative survival rate of patients with CVP measured within 3 hours was significantly higher (66.7% vs. 59.1%; Log-Rank test: χ = 15.810, adjusted P < 0.001); while no significant difference was found in patients with CVP measured between 4 hours and 6 hours and between 7 hours and 12 hours compared with the patients without early CVP measurement within 12 hours (64.4%, 60.3% vs. 59.1%; Log-Rank test: χ values were 5.630 and 0.100, and adjusted P values were 0.053 and > 0.999, respectively). Cox multivariate analysis showed that the Cox proportional risk model was established by taking patients without CVP measurement within 12 hours as reference, timely CVP measurement after ICU admission was associated with reduced 28-day mortality of patients with sepsis [≤ 3 hours: hazard ratio (HR) = 0.65, 95% confidence interval (95%CI) was 0.55-0.77, P < 0.001; 4-6 hours: HR = 0.72, 95%CI was 0.60-0.87, P = 0.001; 7-12 hours: HR = 0.80, 95%CI was 0.66-0.98, P = 0.032] after the confounding variables (gender, age, SOFA score, initial Lac, renal failure, maximal blood glucose and white blood cell count, and minimal platelet count within 24 hours) were adjusted.

Conclusions: Early CVP measurement is associated with decreased 28-day mortality in patients with sepsis. CVP should be considered as a valuable and easily accessible safety parameter during early fluid resuscitation.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201120-00722DOI Listing
July 2021

BinomiRare: A robust test for association of a rare genetic variant with a binary outcome for mixed models and any case-control proportion.

HGG Adv 2021 Jul 12;2(3). Epub 2021 Jun 12.

Framingham Heart Study, Framingham, MA, USA.

Whole-genome sequencing (WGS) and whole-exome sequencing studies have become increasingly available and are being used to identify rare genetic variants associated with health and disease outcomes. Investigators routinely use mixed models to account for genetic relatedness or other clustering variables (e.g., family or household) when testing genetic associations. However, no existing tests of the association of a rare variant with a binary outcome in the presence of correlated data control the type 1 error where there are (1) few individuals harboring the rare allele, (2) a small proportion of cases relative to controls, and (3) covariates to adjust for. Here, we address all three issues in developing a framework for testing rare variant association with a binary trait in individuals harboring at least one risk allele. In this framework, we estimate outcome probabilities under the null hypothesis and then use them, within the individuals with at least one risk allele, to test variant associations. We extend the BinomiRare test, which was previously proposed for independent observations, and develop the Conway-Maxwell-Poisson (CMP) test and study their properties in simulations. We show that the BinomiRare test always controls the type 1 error, while the CMP test sometimes does not. We then use the BinomiRare test to test the association of rare genetic variants in target genes with small-vessel disease (SVD) stroke, short sleep, and venous thromboembolism (VTE), in whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program.
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http://dx.doi.org/10.1016/j.xhgg.2021.100040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321319PMC
July 2021

Risk Factors for Acute Kidney Injury in Critically Ill Neonates: A Systematic Review and Meta-Analysis.

Front Pediatr 2021 14;9:666507. Epub 2021 Jul 14.

Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Acute kidney injury (AKI) is recognized as an independent risk factor for mortality and long-term poor prognosis in neonates. The objective of the study was to identify the risk factors for AKI in critically ill neonates to provide an important basis for follow-up research studies and early prevention. The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, WanFang Med, SinoMed, and VIP Data were searched for studies of risk factors in critically ill neonates. Studies published from the initiation of the database to November 19, 2020, were included. The quality of studies was assessed by the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality (AHRQ) checklist. The meta-analysis was conducted with Stata 15 and drafted according to the guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Seventeen studies (five cohort studies, ten case-control studies, and two cross-sectional studies) were included in meta-analysis, with 1,627 cases in the case group and 5,220 cases in the control group. The incidence of AKI fluctuated from 8.4 to 63.3%. Fifteen risk factors were included, nine of which were significantly associated with an increased risk of AKI in critically ill neonates: gestational age [standardized mean difference (SMD) = -0.31, 95%CI = (-0.51, -0.12), = 0.002], birthweight [SMD = -0.37, 95%CI = (-0.67, -0.07), = 0.015], 1-min Apgar score [SMD = -0.61, 95%CI = (-0.78, -0.43), = 0.000], 5-min Apgar score [SMD = -0.71, 95%CI = (-1.00, -0.41), = 0.000], congenital heart disease (CHD) [odds ratio (OR) = 2.94, 95%CI = (2.08, 4.15), = 0.000], hyperbilirubinemia [OR = 2.26, 95%CI = (1.40, 3.65), = 0.001], necrotizing enterocolitis (NEC) [OR = 6.32, 95%CI = (2.98, 13.42), = 0.000], sepsis [OR = 2.21, 95%CI = (1.25, 3.89), = 0.006], and mechanical ventilation [OR = 2.37, 95%CI = (1.50, 3.75), = 0.000]. Six of them were not significantly associated with AKI in critically ill neonates: age [SMD = -0.25, 95%CI = (-0.54, 0.04), = 0.095], male sex [OR = 1.10, 95%CI =(0.97, 1.24), = 0.147], prematurity [OR = 0.90, 95%CI(0.52, 1.56), = 0.716], cesarean section [OR = 1.52, 95%CI(0.77, 3.01), = 0.234], prenatal hemorrhage [OR = 1.41, 95%CI = (0.86, 2.33), = 0.171], and vancomycin [OR = 1.16, 95%CI = (0.71, 1.89), = 0.555]. This meta-analysis provides a preliminary exploration of risk factors in critically ill neonatal AKI, which may be useful for the prediction of AKI. PROSPERO (CRD42020188032).
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http://dx.doi.org/10.3389/fped.2021.666507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316634PMC
July 2021

ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner.

Exp Cell Res 2021 Sep 30;406(2):112752. Epub 2021 Jul 30.

School of Life Sciences and Biopharmaceutics, Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address:

It has been reported that ACBD3 is closely related to the malignant process of cells, but its role in gastric cancer has not been elucidated. This study aims to investigate the expression and function of ACBD3 in human gastric cancer. The Cancer Genome Atlas (TCGA) database were selected to analyze mRNA levels of ACBD3 in gastric cancer tissues and normal gastric epithelial tissues. qPCR and Western blot were conducted to detect the expression of ACBD3 in two normal gastric epithelial cell lines and five gastric cancer cell lines which were cultured in our laboratory. To exclude differences in individual background between different patients, we further detected the expression of ACBD3 in 8 pairs of malignant/non-malignant clinical gastric tissues. Through the establishment of stable cells, in vitro cell experiments and in vivo xenotransplantation models in mice, the role of ACBD3 in the proliferation of gastric cancer cells has been further explored. AKT inhibitors were used to deeply explore the molecular regulation mechanism of ACBD3. The results showed that the elevated ACBD3 in gastric cancer tissue were positively correlated with the clinical grade and prognosis of gastric cancer. In terms of molecular function, we found that ACBD3 can enhance the production and growth of gastric cancer cells. At the same time, the activation of AKT kinase played an important role in ACBD3's promotion of G1-to-S transition. The experiments generally indicate that ACBD3 is expected to become a potential diagnostic molecule or therapeutic target for gastric cancer.
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http://dx.doi.org/10.1016/j.yexcr.2021.112752DOI Listing
September 2021

Experimental observation of static component generation by Lamb wave propagation in an elastic plate.

Ultrasonics 2021 Dec 24;117:106537. Epub 2021 Jul 24.

College of Aerospace Engineering, Chongqing University, Chongqing 400044, China. Electronic address:

The experimental observation of acoustic radiation induced static component (SC) generation by Lamb wave propagation in an elastic plate is first reported. An experimental approach to directly detect the generated SC of primary Lamb wave propagation in an elastic plate is proposed, where a low-frequency wedge transducer is used to detect the SC pulse generated by primary Lamb wave tone-burst that is excited by a high-frequency wedge transducer. The basic requirements are that the group velocity of primary Lamb wave needs to be equal to that of the s mode at zero frequency (i.e., the SC), and that the central frequency of the low-frequency wedge transducer needs to be near the center of the main lobe frequency range of the generated SC pulse. For this purpose, the S mode whose group velocity is equal to that of the generated SC is selected as the primary Lamb wave, and then the specific mode pair S-s is focused and analyzed. Accompanying propagation of the S mode tone-burst, the generated SC pulse detected with the low-frequency wedge transducer is clearly observed. Through respectively measuring the amplitudes of the S mode and the generated SC for different spatial separation between the transmitting and receiving wedge transducers, the quantitative relationship of the relative nonlinear acoustic parameter with propagation distance is obtained. The experimental results show that the proposed approach can be used to directly detect the generated SC of Lamb wave propagation, and that the said SC does have a cumulative growth effect with propagation distance.
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http://dx.doi.org/10.1016/j.ultras.2021.106537DOI Listing
December 2021
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