Publications by authors named "Jing Tan"

392 Publications

Quantifying the impacts of human mobility restriction on the spread of coronavirus disease 2019: an empirical analysis from 344 cities of China.

Chin Med J (Engl) 2021 Oct 7. Epub 2021 Oct 7.

Chinese Evidence-Based Medicine Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario L8S 4L8, Canada Biostatistics Unit, St Joseph's Healthcare-Hamilton, Ontario L8S 4L8, Canada School of Economics, Sichuan University, Chengdu, Sichuan 610041, China College of Systems Engineering, National University of Defense Technology, Changsha, Hunan 410073, China Department of Global Public Health, Karolinska Institute, Stockholm, Sweden Center for Health Economics and Policy Analysis, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario L8S 4L8, Canada Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19.

Methods: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders.

Results: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities.

Conclusions: Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.
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http://dx.doi.org/10.1097/CM9.0000000000001763DOI Listing
October 2021

A Single Crystal Hybrid Ligand Framework of Copper(II) with Stable Intrinsic Blue-Light Luminescence in Aqueous Solution.

Nanomaterials (Basel) 2021 Sep 2;11(9). Epub 2021 Sep 2.

The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok 10330, Thailand.

Single-crystal solid-liquid dual-phase hybrid organic-inorganic ligand frameworks with reversible sensing response facilitated by external stimuli have received significant attention in recent years. This report presents a significant leap in designing electronic structures that display reversible dual-phase photoluminescence properties from single-crystal hybrid ligand frameworks. Three-dimensional Cu(CNH)Cl complex frameworks were formed through the intermolecular hydrogen bonding and π⋯π stacking supramolecular interactions. The absorption band peaks at 627 nm were assigned to d-d transition showing 10Dq = 15,949 cm and crystal field stabilization energy (CFSE) = 0.6 × 10Dq = 114.4 kJmol, while the ligand-to-metal charge transfer (LMCT) of complexes was displayed at 292 nm. The intense luminescence band results from LMCT present at 397 nm. Considering its structure, air stability, framework forming and stable luminescence in aqueous solution, the Cu(CNH)Cl complex shows potential for luminescence Cu-based sensors using emission intensity to detect heavy metal ion species.
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http://dx.doi.org/10.3390/nano11092281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471168PMC
September 2021

The Influence of Academic Emotions on Learning Effects: A Systematic Review.

Int J Environ Res Public Health 2021 Sep 14;18(18). Epub 2021 Sep 14.

College of Sports Science and Technology, Wuhan Sports University, Wuhan 430205, China.

Academic emotions can have different influences on learning effects, but these have not been systematically studied. In this paper, we objectively evaluate the influence of various academic emotions on learning effects and studied the relationship between positive and negative academic emotions and learning effects by using five electronic databases, including WOS, EMBASE, PubMed, PsycINFO, and Google Scholar. According to established standards, a total of 14 articles from 506 articles were included in the analysis. We divided the 14 studies into nine intervention studies and five observational studies; five of the nine intervention studies found that students who used active learning materials performed better and had higher mental loads than those who used neutral learning materials. Positive academic emotions promoted the learning effect. Four of the five observational studies with high school, college, and postgraduate participants reported that regulating academic emotions can improve learning effects. In conclusion, this paper holds that positive academic emotions are better than negative academic emotions at improving academic performance. In future research, a new method combining multichannel video observation, physiological data, and facial expression data is proposed to capture learners' learning behavior in various learning environments.
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http://dx.doi.org/10.3390/ijerph18189678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472431PMC
September 2021

Assessing Clinical Effects of Traditional Chinese Medicine Interventions: Moving Beyond Randomized Controlled Trials.

Front Pharmacol 2021 7;12:713071. Epub 2021 Sep 7.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

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http://dx.doi.org/10.3389/fphar.2021.713071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452912PMC
September 2021

The short-term safety and effectiveness of a new distal perforating stent graft in Type B aortic dissection: a retrospective study.

BMC Cardiovasc Disord 2021 Sep 21;21(1):457. Epub 2021 Sep 21.

Vascular Intervention Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.

Background: Spinal artery ischemia (SCI) events can result from over coverage of the descending thoracic aorta with a coated stent during Thoracic Endovascular Aortic Repair (TEVAR). The aim of this study was to determine whether a new distal perforating stent could reduce the incidence of spinal cord ischemia while remodeling the true lumen.

Methods: TBAD patients treated with Talos stent in the vascular surgery Department of Yan 'an Hospital affiliated to Kunming Medical University between December 2017 and October 2019 were retrospectively analyzed to investigate the short-term safety and effectiveness of Talos stent.

Results: A total of the 20 patients, including 14 males and 6 females, with an average age of 52.65 ± 8.98 years (range 37-68 years), were included in the analysis. Stent-grafts were successfully implanted in all patients under local anesthesia, with a technical success rate of 100%. The average operation time was 50.75 ± 13.01 min. A total of 2 cases (10%) presented chest pain associated with intercostal artery ischemia that was relieved on the 3rd and 5th postoperative day, respectively. Postoperative mean follow-up was 16.15 ± 3.99 months. No paraplegia or other complications occurred. And stenting did not induce new tears. No migration, deformation, or fracture of the stents occurred. There was a significant difference in the remolding of the true lumen preoperatively and at 12 months postoperatively (P < 0.05).

Conclusions: Talos stent has achieved satisfactory clinical treatment results in short term.
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http://dx.doi.org/10.1186/s12872-021-02270-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456669PMC
September 2021

Treatment Outcomes and Survival Patterns of Asian Patients With Relapsed/Refractory Mantle Cell Lymphoma.

J Hematol 2020 Aug 30;10(4):187-195. Epub 2021 Aug 30.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore.

Background: Mantle cell lymphoma (MCL) is widely considered an incurable malignancy even with current therapies and relapsed/refractory (R/R) disease to primary treatment remains common. With improved treatment guidelines and the advent of novel agents, patients are increasingly being treated with more lines of regimens. However, outcomes after each line of treatment remain poorly characterized, especially in the Asian population. In this paper, we described the survival outcomes in a group of R/R MCL patients.

Methods: We retrospectively studied 35 patients with R/R MCL between 1998 and 2020 at the National Cancer Centre Singapore. Patients were followed longitudinally throughout their disease course. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method.

Results: The median OS and PFS from diagnosis were 105 and 40 months, respectively. After first relapse, the median OS and PFS were 52 and 19 months, post-second relapse 32 and 8 months, and post-third relapse 12 and 6 months, respectively. Patients older than 65 years at first relapse had shorter survival (median OS: 22 vs. 55 months, P = 0.0417; median PFS: 9 vs. 29 months, P = 0.001). Early treatment failure after first line therapy was also associated with worse survival outcomes (median OS: 13 vs. 55 months, P < 0.001; median PFS: 9 vs. 26 months, P < 0.001).

Conclusion: With each relapse, survival outcomes for patients with MCL are worse. Novel treatment and contemporary outcomes of R/R MCL are encouraging and support the need for continued research in this area.
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http://dx.doi.org/10.14740/jh890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425802PMC
August 2020

CREBBP cooperates with the cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory diffuse large B-cell lymphoma.

Cancer Lett 2021 Sep 2;521:268-280. Epub 2021 Sep 2.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China. Electronic address:

Diffuse large B-cell lymphoma (DLBCL) exhibits frequent inactivating mutations of the histone acetyltransferase CREBBP, highlighting the attractiveness of targeting CREBBP deficiency as a therapeutic strategy. In this study, we demonstrate that chidamide, a novel histone deacetylase (HDAC) inhibitor, is effective in treating a subgroup of relapsed/refractory DLBCL patients, achieving an overall response rate (ORR) of 25.0% and a complete response (CR) rate of 15.0%. However, the clinical response to chidamide remains poor, as most patients exhibit resistance, hampering the clinical utility of the drug. Functional in vitro and in vivo studies have shown that CREBBP loss of function is correlated with chidamide sensitivity, which is associated with modulation of the cell cycle machinery. A combinatorial drug screening of 130 kinase inhibitors targeting cell cycle regulators identified AURKA inhibitors, which inhibit the G2/M transition during the cell cycle, as top candidates that synergistically enhanced the antitumor effects of chidamide in CREBBP-proficient DLBCL cells. Our study demonstrates that CREBBP inactivation can serve as a potential biomarker to predict chidamide sensitivity, while combination of an AURKA inhibitor and chidamide is a novel therapeutic strategy for the treatment of relapsed/refractory DLBCL.
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http://dx.doi.org/10.1016/j.canlet.2021.09.002DOI Listing
September 2021

Targeting enhancer reprogramming to mitigate MEK inhibitor resistance in preclinical models of advanced ovarian cancer.

J Clin Invest 2021 Oct;131(20)

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

Ovarian cancer is characterized by aberrant activation of the mitogen-activated protein kinase (MAPK), highlighting the importance of targeting the MAPK pathway as an attractive therapeutic strategy. However, the clinical efficacy of MEK inhibitors is limited by intrinsic or acquired drug resistance. Here, we established patient-derived ovarian cancer models resistant to MEK inhibitors and demonstrated that resistance to the clinically approved MEK inhibitor trametinib was associated with enhancer reprogramming. We also showed that enhancer decommissioning induced the downregulation of negative regulators of the MAPK pathway, leading to constitutive ERK activation and acquired resistance to trametinib. Epigenetic compound screening uncovered that HDAC inhibitors could alter the enhancer reprogramming and upregulate the expression of MAPK negative regulators, resulting in sustained MAPK inhibition and reversal of trametinib resistance. Consequently, a combination of HDAC inhibitor and trametinib demonstrated a synergistic antitumor effect in vitro and in vivo, including patient-derived xenograft mouse models. These findings demonstrated that enhancer reprogramming of the MAPK regulatory pathway might serve as a potential mechanism underlying MAPK inhibitor resistance and concurrent targeting of epigenetic pathways and MAPK signaling might provide an effective treatment strategy for advanced ovarian cancer.
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http://dx.doi.org/10.1172/JCI145035DOI Listing
October 2021

Low incidence of non-COVID-19 community respiratory viral infections amongst adults with haematological malignancies during the COVID-19 pandemic.

J Intern Med 2021 Aug 30. Epub 2021 Aug 30.

Department of Infection Prevention and Epidemiology, Singapore General Hospital, Singapore.

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http://dx.doi.org/10.1111/joim.13388DOI Listing
August 2021

[Fascia lata graft for the treatment of spontaneous ruptures of multiple extensor tendons on wrist joint:a case report].

Zhongguo Gu Shang 2021 Aug;34(8):770-2

Department of Orthopaedics, People's Hospital of Three Gorges University & The First People's Hospital of Yichang, Yichang 443000, Hubei, China.

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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.08.015DOI Listing
August 2021

Rationale, design and population description of the CREDENCE study: cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records.

Eur J Epidemiol 2021 Aug 22. Epub 2021 Aug 22.

Section of Epidemiology and Biostatistics, School of Population Health, University of Auckland, 30 Park Avenue, Grafton, Auckland, 1023, New Zealand.

The cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records (CREDENCE) study is a unique prospectively designed investigation of cardiovascular risk in two large contemporary cohorts of people with type 2 diabetes from New Zealand (NZ) and China. The study was designed to derive equivalent cardiovascular risk prediction equations in a developed and a developing country, using the same epidemiological and statistical methodology. Two similar cohorts of people with type 2 diabetes were identified from large general population studies in China and New Zealand, which had been generated from longitudinal electronic health record systems. The CREDENCE study aims to determine whether cardiovascular risk prediction equations derived in patients with type 2 diabetes in a developed country are applicable in a developing country, and vice versa, by deriving and validating equivalent diabetes-specific cardiovascular risk prediction models from the two countries. Baseline data in CREDENCE was collected from October 2004 in New Zealand and from January 2010 in China. In the first stage of CREDENCE, a total of 93,207 patients (46,649 from NZ and 46,558 from China) were followed until December 31st 2018. Median follow-up was 7.0 years (New Zealand) and 5.7 years (China). There were 5926 (7.7% fatal) CVD events in the New Zealand cohort and 3650 (8.8% fatal) in the Chinese cohort. The research results have implications for policy makers, clinicians and the public and will facilitate personalised management of cardiovascular risk in people with type 2 diabetes worldwide.
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http://dx.doi.org/10.1007/s10654-021-00795-9DOI Listing
August 2021

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

HPB (Oxford) 2021 Jul 26. Epub 2021 Jul 26.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic.

Methods: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic.

Results: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC.

Discussion: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.
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http://dx.doi.org/10.1016/j.hpb.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312214PMC
July 2021

Benefits and barriers: a qualitative study on online social participation among widowed older adults in Southwest China.

BMC Geriatr 2021 08 3;21(1):450. Epub 2021 Aug 3.

School of Nursing, Army Medical University / Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.

Background: With the development of digital media, online activities are increasingly becoming part of the daily life of older adults. Widowed older adults generally would face changes in social interactions and activities due to widowhood; thus, the importance of online participation may be more prominent in this population. However, a detailed evidence on the experiences of online social participation among widowed older adults is relatively sparse. This study aimed to explore widowed older adults' perceptions regarding online social participation in southwestern China.

Methods: This study adopted a qualitative approach. Semi-structured, in-depth individual interviews were conducted with 19 widowed older adults between September-December 2020. Thematic analysis was applied to analyse the data.

Results: Two major themes, "benefits" and "barriers" were identified from the original data analysis. Subcategories concerning the theme "benefits" were "benefit perception (convenience, flexible time, supplementation)", "health promotion", "emotional comfort", and "social connection". Subcategories of "barriers" were "worries: personal economic loss", "concerns: security of digital device", "troubles: the diversity of online social participation", and "difficulties: using digital media".

Conclusions: Social participation of widowed older adults in southwestern China has begun to be integrated into the digital world; however, it remains at an early stage with the simple purpose of engagement. The older adults may face many challenges for online social participation. Although there are barriers and challenges in online social participation, widowed older adults can reap its benefits, which can be used as an important measure to facilitate a fulfilling life and successful ageing. There is no doubt that online social participation will become a trend within the foreseeable future. Family, friends and health care professionals should pay more attention to the needs of online social participation in widowed older adults and provide adequate support for them to achieve a meaningful life.
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http://dx.doi.org/10.1186/s12877-021-02381-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329635PMC
August 2021

Efficacy of Anlotinib for the Treatment of Angiosarcoma of the Face and Neck: A Case Report.

Front Oncol 2021 28;11:596732. Epub 2021 Jun 28.

Department of Medical Oncology, Chongqing University Three Gorges Hospital, Chongqing, China.

Angiosarcoma of the face and neck is a rare soft tissue sarcoma with a high degree of malignancy. The current treatment methods mainly rely on a combination of surgery and radiotherapy and/or chemotherapy. However, the options for drug treatment are very limited and surgery can be difficult to carry out due to the location of the tumor, so the efficacy of first-line drugs needs to be constantly explored. A case of angiosarcoma of the head and face diagnosed by biopsy is reported here. The patient received an oral anlotinib hydrochloride capsule once a day (12 mg on days 1 - 14/1 week off for a 21-day cycle) due to the difficulty of surgery. Until now (April, 2020), after 10 months of treatment, the patient's scalp and facial lesions have gradually reduced and the partial response and progression-free survival of this patient were good, with moderate or tolerable adverse events. This approach provides a new approach for the clinical treatment of malignant angiosarcoma of the face and neck with anlotinib as first-line therapy.
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http://dx.doi.org/10.3389/fonc.2021.596732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273654PMC
June 2021

Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit.

Cell Rep 2021 Jul;36(1):109338

Clem Jones Centre for Ageing Dementia Research, The University of Queensland, Brisbane, QLD 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

NMDA receptor (NMDAR)-dependent Ca influx underpins multiple forms of synaptic plasticity. Most synaptic NMDAR currents in the adult forebrain are mediated by GluN2A-containing receptors, which are rapidly inserted into synapses during long-term potentiation (LTP); however, the underlying molecular mechanisms remain poorly understood. In this study, we show that GluN2A is phosphorylated at Ser-1459 by Ca/calmodulin-dependent kinase IIα (CaMKIIα) in response to glycine stimulation that mimics LTP in primary neurons. Phosphorylation of Ser-1459 promotes GluN2A interaction with the sorting nexin 27 (SNX27)-retromer complex, thereby enhancing the endosomal recycling of NMDARs. Loss of SNX27 or CaMKIIα function blocks the glycine-induced increase in GluN2A-NMDARs on the neuronal membrane. Interestingly, mutations of Ser-1459, including the rare S1459G human epilepsy variant, prolong the decay times of NMDAR-mediated synaptic currents in heterosynapses by increasing the duration of channel opening. These findings not only identify a critical role of Ser-1459 phosphorylation in regulating the function of NMDARs, but they also explain how the S1459G variant dysregulates NMDAR function.
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http://dx.doi.org/10.1016/j.celrep.2021.109338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313361PMC
July 2021

Life-and-Death Attitude and Its Formation Process and End-of-Life Care Expectations Among the Elderly Under Traditional Chinese Culture: A Qualitative Study.

J Transcult Nurs 2021 Jun 12:10436596211021490. Epub 2021 Jun 12.

Army Medical University (Third Military Medical University), Chongqing, People's Republic of China.

Introduction: With the global aging process intensified, the demand for end-of-life care has surged, especially in China. However, its development is restricted. Understanding the life and death attitude among the elderly and its formation process, and clarifying their needs, are so important to promote social popularization of end-of-life care.

Methodology: This qualitative study included 20 elderly residents in Nan and Shuangbei Communities, Chongqing City, People's Republic of China. Data were collected through semistructured in-depth individual interviews and processed by thematic analysis method.

Results: Three themes and eight subthemes were identified: Characteristics of formation process (passive thinking, closed and single), life-and-death attitude (cherish and enjoy life, quality of life priority, let death take its course) and expectations of end-of-life care (preferences, basic needs, good death).

Discussion: Life-and-death attitude and end-of-life care expectations of the elderly support the development and delivery of end-of-life care. Furthermore, the individual-family-hospital linkage discussion channel needs to be further explored.
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http://dx.doi.org/10.1177/10436596211021490DOI Listing
June 2021

Vitamin K2 (Menaquinone-7) supplementation does not affect vitamin K-dependent coagulation factors activity in healthy individuals.

Medicine (Baltimore) 2021 Jun;100(23):e26221

Department of Hematology, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.

Background: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available.

Objectives: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment.

Design: Forty healthy volunteers between 25 and 40 years of age were recruited. Menaquinone-7 (MK-7) was administrated at 90 μg for 30 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration.

Results: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30 days of MK-7 supplementation.

Conclusions: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment.
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http://dx.doi.org/10.1097/MD.0000000000026221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202544PMC
June 2021

Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP-AMP Synthase.

J Med Chem 2021 06 27;64(11):7667-7690. Epub 2021 May 27.

Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

The activation of cyclic GMP-AMP synthase (cGAS) by double-stranded DNA is implicated in the pathogenesis of many hyperinflammatory and autoimmune diseases, and the cGAS-targeting small molecule has emerged as a novel therapeutic strategy for treating these diseases. However, the currently reported cGAS inhibitors are far beyond maturity, barely demonstrating in vivo efficacy. Inspired by the structural novelty of compound (G140), we conducted a structural optimization on both its side chain and the central tricyclic core, leading to several subseries of compounds, including those unexpectedly cyclized complex ones. Compound bearing an -glycylglycinoyl side chain was identified as the most potent one with cellular IC values of 1.38 and 11.4 μM for h- and m-cGAS, respectively. Mechanistic studies confirmed its direct targeting of cGAS. Further, compound showed superior in vivo anti-inflammatory effects in the lipopolysaccharide-induced mouse model. The encouraging result of compound provides solid evidence for further pursuit of cGAS-targeting inhibitors as a new anti-inflammatory treatment.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00398DOI Listing
June 2021

GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling.

Cancer Lett 2021 Aug 21;514:90-102. Epub 2021 May 21.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China. Electronic address:

Effective treatment regimens for triple-negative breast cancer (TNBC) are relatively scarce due to a lack of specific therapeutic targets. Epidermal growth factor receptor (EGFR) signaling is highly active in TNBC and is associated with poor prognosis. Most EGFR antagonists, which significantly improve outcome in lung and colon cancer, have shown limited clinical effects in breast cancer. However, limiting EGFR expression in TNBC is a potential strategy for improving the clinical efficacy of EGFR antagonists. Here, we found that the gamma-aminobutyric acid type A receptor π subunit (GABRP), as a membrane protein enriched in TNBC stem cells, interacted with EGFR and significantly sustained its expression, resulting in stemness maintenance and chemotherapy resistance. Silencing GABRP induced down-regulation of EGFR signaling, which hindered cell stemness and enhanced sensitivity to chemotherapies, including paclitaxel, doxorubicin, and cisplatin. We also identified that retigabine, an FDA-approved drug for adjunctive treatment of seizures, increased the sensitivity of EGFR to gefitinib in gefitinib-resistant cells. Our findings show that GABRP can sustain the stemness of TNBC via modulating EGFR expression, suggesting that GABRP may be a potential therapeutic target that can address EGFR inhibitor resistance in TNBC.
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http://dx.doi.org/10.1016/j.canlet.2021.04.028DOI Listing
August 2021

Mesenchymal stem cells treatment improves vascularization, muscle contraction and VEGF expression, and reduces apoptosis in rat ischemic hind limb.

Biochem Pharmacol 2021 Aug 21;190:114530. Epub 2021 Apr 21.

Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.

Peripheral arterial disease (PAD) is an increasingly common narrowing of the peripheral arteries that can lead to lower limb ischemia, muscle weakness and gangrene. Surgical vein or arterial grafts could improve PAD, but may not be suitable in elderly patients, prompting research into less invasive approaches. Mesenchymal stem cells (MSCs) have been proposed as potential therapy, but their effectiveness and underlying mechanisms in limb ischemia are unclear. We tested the hypothesis that treatment with naive MSCs (nMSCs) or MSCs expressing CD146 (MSCs) could improve vascularity and muscle function in rat model of hind-limb ischemia. Sixteen month old Sprague-Dawley rats were randomly assigned to 4 groups: sham-operated control, ischemia, ischemia + nMSCs and ischemia+MSCs. After 4 weeks of respective treatment, rat groups were assessed for ischemic clinical score, Tarlov score, muscle capillary density, TUNEL apoptosis assay, contractile force, and vascular endothelial growth factor (VEGF) mRNA expression. MSCs showed greater CD146 mRNA expression than nMSCs. Treatment with nMSCs or MSCs improved clinical and Tarlov scores, muscle capillary density, contractile force and VEGF mRNA expression in ischemic limbs as compared to non-treated ischemia group. The improvements in muscle vascularity and function were particularly greater in ischemia+MSCs than ischemia + nMSCs group. TUNEL positive apoptotic cells were least abundant in ischemia+MSCs compared with ischemia + nMSCs and non-treated ischemia groups. Thus, MSCs particularly those expressing CD146 improve vascularity, muscle function and VEGF expression and reduce apoptosis in rat ischemic limb, and could represent a promising approach to improve angiogenesis and muscle function in PAD.
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http://dx.doi.org/10.1016/j.bcp.2021.114530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316322PMC
August 2021

Reduction in respiratory viral infections among hospitalized older adults during the COVID-19 pandemic.

J Am Geriatr Soc 2021 07 23;69(7):1745-1747. Epub 2021 Apr 23.

Department of Infection Prevention and Epidemiology, Singapore General Hospital, Singapore.

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http://dx.doi.org/10.1111/jgs.17179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251136PMC
July 2021

Development of Potent NEDD8-Activating Enzyme Inhibitors Bearing a Pyrimidotriazole Scaffold.

J Med Chem 2021 05 15;64(9):6161-6178. Epub 2021 Apr 15.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

The ubiquitin-like protein NEDD8 is a critical signaling molecule implicated in the functional maintenance and homeostasis of cells. Dysregulation of this process is involved in a variety of human diseases, including cancer. Therefore, NEDD8-activating enzyme E1 (NAE), the only activation enzyme of the neddylation pathway, has been an emergent anticancer target. In view of the single-agent modest response of the clinical NAE inhibitor, pevonedistat (compound , MLN4924), efforts on development of new inhibitors with both high potency and better safety profiles are urgently needed. Here, we report a structural hopping strategy by optimizing the central deazapurine framework and the solvent interaction region of compound , leading to compound bearing a pyrimidotriazole scaffold. Compound not only has compatible potency in the biochemical and cell assays but also possesses improved pharmacokinetic (PK) properties than compound . In vivo, compound showed significant antitumor efficacy and good safety in xenograft models.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00242DOI Listing
May 2021

The ups, downs and new trends of IDO1 inhibitors.

Bioorg Chem 2021 05 10;110:104815. Epub 2021 Mar 10.

Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Cancer immunotherapy has become an emerging driving force in the development of innovative strategies to fight against cancer. Despite the significant clinical benefits that many cancer patients have gained, the generally average response rate of ~ 20% is far behind the expectation for immune checkpoint inhibitors (ICIs). Combination of ICIs with indoleamine 2,3-dioxygenase-1 (IDO1) inhibitors is considered as an alternative solution and has proved effective in tremendous preclinical studies. However, the failure of phase III ECHO-301/KEYNOTE-252 trial seriously dampened the enthusiasm on the rationality of IDO1-targeting strategy. Fortunately, in spite of the ups and downs in the developmental journey of IDO1 inhibitors, multiple new approaches have been proposed to bridge the gap between lab to the clinic. Here, we review the recent advances in the development of small molecule inhibitors targeting IDO1 especially the new trend of IDO1 inhibitors after ECHO-301 clinical trials, including dual or pan-inhibitors targeting IDO1 and TDO or IDO2, apo-IDO1 inhibitors, IDO1 PROTACs, as well as other IDO1 inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2021.104815DOI Listing
May 2021

Association between migration status and caesarean section delivery based on a modified Robson classification in China.

BMC Pregnancy Childbirth 2021 Mar 17;21(1):215. Epub 2021 Mar 17.

The Women and Children's Health Care Department, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200000, China.

Background: China has one of the highest caesarean section (C-Section) rates in the world. In recent years, China has been experiencing a massive flow of migration due to rapid urbanization. In this study, we aimed to differentiate the rates of C-Section between migrants and residents, and explore any possible factors which may moderate the association between migrant status and C-Section rates.

Methods: We conducted a retrospective cohort study in Shanghai, China. All deliveries were classified using the modified Robson Classification. The association between women's migrant status and C-Section rates was assessed using the Poisson regression of sandwich estimation, after adjusting for possible factors.

Results: Of the 40,621 women included in the study, 66.9% were residents and 33.1% were internal migrants. The rate of C-Section in migrants was lower than that of residents in all subjects (39.9 and 47.7%) and in group 1 subjects (based on the Robson Classification) using a modified Robson Classification. There was an association between migrant status and caesarean delivery on maternal request that was statistically significant (RR = 0.664, p < 0.001), but the association was weakened after adjusting for such factors as maternal age at delivery (aRR = 0.774, p = 0.02), ethnicity (aRR = 0.753, p < 0.001), health insurance (aRR = 0.755, p < 0.001), and occupation (aRR = 0.747, p = 0.004), but had no significant changes when adjusting for health conditions (aRR = 0.668, p = 0.001) and all considering variables (aRR = 0.697, p = 0.002). In group 1 subjects, the effect of migrant status on maternal requested intrapartum C-Section was also statistically significant (RR = 0.742, p = 0.004).

Conclusion: C-Section rates are lower among migrant women than residents, especially on maternal request. The medical practitioners should further reinforce the management of elective C-Section in resident women.
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http://dx.doi.org/10.1186/s12884-021-03708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971954PMC
March 2021

Time-Dependent Phosphorescence Colors from Carbon Dots for Advanced Dynamic Information Encryption.

Adv Mater 2021 Apr 12;33(16):e2006781. Epub 2021 Mar 12.

Institute of Micro-Nano Optoelectronics and Terahertz Technology, School of Mechanical Engineering, Jiangsu University, Zhenjiang, 212013, P. R. China.

The development of phosphorescent materials with time-dependent phosphorescence colors (TDPCs) is of considerable interest for application in advanced dynamic information encryption. In this study, TDPC is realized in carbon dots (CDs) synthesized by the one-pot hydrothermal treatment of levofloxacin. CD ink printed on paper ([email protected]) exhibits a change in phosphorescence color from orange to green, 1 s after irradiation with 395 nm light. However, when irradiated with wavelengths shorter or longer than 395 nm, the [email protected] exhibits only green or red phosphorescence, respectively. The red and green phosphorescence originates from the low-energy surface oxide triplet state and high-energy N-related triplet state, respectively. When irradiated with a suitable light energy (around 395 nm wavelength), the two phosphorescent centers can be simultaneously activated, emitting red and green phosphorescence with different decay rates. The red and green phosphorescence merge into an orange phosphorescence initially, exhibiting the TDPC phenomenon. Based on the unusual phosphorescent properties of the CDs, a kind of multilevel, dynamic phosphorescence colored 3D code is designed for advanced dynamic information encryption.
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http://dx.doi.org/10.1002/adma.202006781DOI Listing
April 2021

Low incidence of venous thrombosis but high incidence of arterial thrombotic complications among critically ill COVID-19 patients in Singapore.

Thromb J 2021 Mar 8;19(1):14. Epub 2021 Mar 8.

Department of Haematology-oncology, National University Cancer Institute, Singapore, Singapore.

Background: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients.

Method And Results: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16).

Conclusions: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.
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http://dx.doi.org/10.1186/s12959-021-00268-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938262PMC
March 2021

How does perceived residential environment quality influence life satisfaction? Evidence from urban China.

J Community Psychol 2021 Sep 5;49(7):2454-2471. Epub 2021 Mar 5.

Department of Civil and Environmental Engineering, Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Japan.

Against the background of fast-paced aging and urbanization in China, the current study proposed a "Residential environment-Emotional health-Life satisfaction" framework to investigate the associations among perceived residential environment quality (PREQ), positive affect (PA), social trust (ST), and life satisfaction (LS) of old adults. Data used were from a nationwide survey and covered 3825 people aged 60 years or older living in urban communities. The partial least squares-structural equation modeling approach was adopted to verify hypotheses. The results found that (1) PREQ, PA, and ST were positively correlated with LS; (2) ST mediated the relationship between PREQ and LS; and (3) people who are men, living without children, high environmental perception, and with a workout habit were more sensitively to PREQ. These findings indicate that improving the residential environment helps to promote the mental health of the Chinese urban elderly, which may have some implications for establishing an age-friendly community.
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http://dx.doi.org/10.1002/jcop.22545DOI Listing
September 2021
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