Publications by authors named "Li Li"

11,572 Publications

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Impact of reduced anthropogenic emissions on chemical characteristics of urban aerosol by individual particle analysis.

Chemosphere 2022 May 23:135013. Epub 2022 May 23.

Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, 100029, China. Electronic address:

A single particle aerosol mass spectrometer was deployed in a heavily polluted area of China during a coronavirus lockdown to explore the impact of reduced anthropogenic emissions on the chemical composition, size distributions, mixing state, and secondary formation of urban aerosols. Ten particle groups were identified using an adaptive resonance network algorithm. Increased atmospheric oxidation during the lockdown period (LP) resulted in a 42.2%-54% increase in the major NaK-SN particle fraction relative to the normal period (NP). In contrast, EC-aged particles decreased from 31.5% (NP) to 23.7% (LP), possibly due to lower emissions from motor vehicles and coal combustion. The peak particle size diameter increased from 440 nm during the NP to 500 nm during LP due to secondary particle formation. High proportions of mixed NO indicate extensive particle aging. Correlations between secondary organic (CHO, oxalate) and secondary inorganic species (NO, HSO and NH) versus oxidants (O = O + NO) and relative humidity (RH) indicate that increased atmospheric oxidation promoted the generation of secondary species, while the effects of RH were more complex. Differences between the NP and LP show that reductions in primary emissions had a remarkable impact on the aerosol particles. This study provides new insights into the effects of pollution emissions on atmospheric reactions and the specific aerosol types in urban regions.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135013DOI Listing
May 2022

Follow-up frequency and clinical outcomes in patients with type 2 diabetes: A prospective analysis based on multicenter real-world data.

J Diabetes 2022 May;14(5):306-314

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: To determine whether the follow-up frequency for type 2 diabetes mellitus (T2DM) patients in the National Metabolic Management Centers (MMCs) leads to different clinical outcomes.

Methods: A total of 19 908 T2DM patients with at least 6 months of facility-based follow-up were recruited in MMCs between June 2017 and April 2021 and divided into lower-frequency and higher-frequency follow-up (LFF and HFF) groups according to the median follow-up frequency of 2.0 (interquartile range 1.2) times per year. Metabolic parameters at baseline and at the last follow-up visit were analyzed. Multivariable linear regression models were performed to assess the relationship between follow-up frequency and between-group percentage changes, adjusting for the major covariables. Additional stratified analyses were conducted to evaluate the metabolic outcomes in the subgroups.

Results: The characteristics of the participants in the LFF and HFF groups were significantly different at baseline. Participants had significant improvements in multiple metabolic parameters after follow-up. Patients with HFF showed significantly greater decrease in percentage changes of fasting blood glucose (-4.95% ± 37.96% vs -2.21% ± 43.08%, P < .0001) and glycosylated hemoglobin (HbA1c) (-12.14% ± 19.78% vs -9.67% ± 20.29%, P < .0001) after adjustments compared to those with LFF. Furthermore, stratification analyses showed that significant between-group percentage changes of HbA1c were observed in those with younger age (<55 years) and higher HbA1c (>9%) at baseline (P for interaction <.001).

Conclusions: HFF is associated with better metabolic outcomes. Participants, especially with younger age or worse HbA1c at baseline in the HFF group achieved better glycemic control than those in the LFF group.
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http://dx.doi.org/10.1111/1753-0407.13271DOI Listing
May 2022

Atropisomeric 9,10-dihydrophenanthrene/bibenzyl trimers with anti-inflammatory and PTP1B inhibitory activities from .

Org Biomol Chem 2022 May 25. Epub 2022 May 25.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Two pairs of novel trimeric dihydrophenanthrene-bibenzyl-dihydrophenanthrene enantiomers (1 and2), the first examples of a dihydrophenanthrene dimer linked to a bibenzyl or dihydrophenanthrene through a C--C bond (3 and4), and a pair of rare polymers with a bibenzyl connected to C-8' of the dihydrophenanthro[]furan moiety a methylene (5), together with four known compounds (6-9) were isolated from the tubers of . Their structures including the absolute configurations were determined using spectroscopic data analysis and ECD and NMR calculations, combined with the exciton chirality method or the reversed helicity rule. The atropisomerism of dihydrophenanthrenes and related polymers was considered based on their chiral optical properties, and QM torsion profile calculations, which revealed the racemic mixture form of the polymers. Compounds 4, 5b, 6a and 7b significantly inhibited the production of NO in LPS-induced BV-2 cells, with IC values ranging from 0.78 to 5.52 μM. Further mechanistic study revealed that 7b suppressed the expression of iNOS, and suppressed the phosphorylation of the p65 subunit to regulate the NF-κB signaling pathway. Furthermore, compounds 2b, 5a, 5b, 7a and 7b displayed significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC values of 3.43-12.30 μM.
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http://dx.doi.org/10.1039/d2ob00489eDOI Listing
May 2022

Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells.

Mol Psychiatry 2022 May 24. Epub 2022 May 24.

Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY, 14203, USA.

The degeneration of nigral (A9) dopaminergic (DA) neurons causes motor symptoms in Parkinson's disease (PD). We use small-molecule compounds to direct the differentiation of human induced pluripotent stem cells (iPSCs) to A9 DA neurons that share many important properties with their in vivo counterparts. The method generates a large percentage of TH neurons that express appropriate A9 markers, such as GIRK2 and ALDH1A1, but mostly not the A10 marker CALBINDIN. Functionally, they exhibit autonomous pacemaking based on L-type voltage-dependent Ca channels and show autoreceptor-dependent regulation of dopamine release. When transplanted in the striatum of 6-OHDA-lesioned athymic rats, the human A9 DA neurons manifest robust survival and axon outgrowth, and ameliorate motor deficits in the rat PD model. The ability to generate patient-specific A9 DA autonomous pacemakers will significantly improve PD research and facilitate the development of disease-modifying therapies.
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http://dx.doi.org/10.1038/s41380-022-01628-1DOI Listing
May 2022

PIKfyve inhibitors against SARS-CoV-2 and its variants including Omicron.

Signal Transduct Target Ther 2022 May 24;7(1):167. Epub 2022 May 24.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, 361102, Xiamen, Fujian, China.

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http://dx.doi.org/10.1038/s41392-022-01025-8DOI Listing
May 2022

weFrontline Therapy Options for Adults with Newly Diagnosed Severe Aplastic Anemia: Intensive immunosuppressive therapy Plus Eltrombopag or Matched Sibling Donor Hematopoietic Stem Cell Transplantation?

Transplant Cell Ther 2022 May 21. Epub 2022 May 21.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are two major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin (r-ATG) or porcine-antilymphocyte globulin (p-ALG), cyclosporin plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (P=0.97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), P=0.04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% vs. 85.7%, P=0.04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% vs. 15.7%, P<0.001; OR: 97.9% vs. 72.6%, P=0.001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.
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http://dx.doi.org/10.1016/j.jtct.2022.05.027DOI Listing
May 2022

Spatiotemporal effects of urban ecological land transitions to thermal environment change in mega-urban agglomeration.

Sci Total Environ 2022 May 21:156158. Epub 2022 May 21.

Institute of Geographic Sciences and Natural Resources Research, Key Laboratory of Regional Sustainable Development Modeling, Chinese Academy of Sciences, Beijing 100101, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Urban ecological land transitions (UELTs) have far-reaching effects on the thermal environment, but their dynamic effects in urban agglomerations remain poorly understood. This study defines the UELT concept and quantifies its spatiotemporal effects and driving mechanisms on land surface temperature interdecadal variations (LSTIVs) in the Guangdong-Hong Kong-Macao Greater Bay Area using remote sensing, fuzzy overlay, shape-weighted landscape evolution index, and Geodetector methods. The results showed that UELTs shifted from degradation, increasing pressure, and decreasing vegetation proportion in the central city to scattered restoration, pressure relief, and increasing vegetation proportion in 2010-2020. LSTIVs simultaneously transitioned from rapid growth and contiguous expansion to reduction and dispersion. Moreover, the contribution of UELTs to LSTIVs increased by 19.49% from 2000 to 2020, and gradually shifted from being driven by dominant transition (isolating and adjacent degradation) (mean q = 0.58) to recessive transition (increased population and construction land pressure) (mean q = 0.62), where q is the determinant power. Interactions between edge-expansion and infilling restoration with the blue-green ratio (BGR; i.e., ratio of waterbodies to vegetation), habitat quality, and population layout had significant effects on LSTIVs. In addition, the relative magnitude of the effect of UEL restoration-degradation and BGR on LSTIVs was not fixed, but rather related to their interaction effect and the urban agglomeration development stage. Therefore, in addition to promoting an increase in UEL, optimizing the landscape structure of UEL (e.g., increasing aggregation and connectivity, adjusting BGR) and UEL distribution with other human factors are also crucial to reduce the urban thermal environment.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156158DOI Listing
May 2022

Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement.

JAMA 2022 May 24. Epub 2022 May 24.

Tufts University School of Medicine, Boston, Massachusetts.

Importance: Impairment of visual acuity is a serious public health problem in older adults. The number of persons 60 years or older with impaired visual acuity (defined as best corrected visual acuity worse than 20/40 but better than 20/200) was estimated at 2.91 million in 2015, and the number who are blind (defined as best corrected visual acuity of 20/200 or worse) was estimated at 760 000. Impaired visual acuity is consistently associated with decreased quality of life in older persons, including reduced ability to perform activities of daily living, work, and drive safely, as well as increased risk of falls and other unintentional injuries.

Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for impaired visual acuity in older adults.

Population: Asymptomatic adults 65 years or older who present in primary care without known impaired visual acuity and are not seeking care for vision problems.

Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in asymptomatic older adults. The evidence is lacking, and the balance of benefits and harms cannot be determined. More research is needed.

Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement).
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http://dx.doi.org/10.1001/jama.2022.7015DOI Listing
May 2022

Unique Probiotic Properties and Bioactive Metabolites of Saccharomyces boulardii.

Probiotics Antimicrob Proteins 2022 May 24. Epub 2022 May 24.

College of Biotechnology Engineering, Sichuan University of Science and Engineering, Yibin, 644000, China.

Saccharomyces boulardii (S. boulardii) is a probiotic and is widely used to improve the nutritional and functional value of food. This study aimed to compare the probiotic properties of S. boulardii and Saccharomyces cerevisiae. A series of in vitro probiotic experiments was performed, including simulated gastrointestinal digestion, bile salt tolerance, hydrophobicity, self-aggregation, and antioxidant and antibacterial properties. Self-aggregation and hydrophobic properties of S. boulardii were relatively poor, but they showed high tolerance, antioxidant properties, and broad antibacterial properties. In addition, non-targeted metabolomics was used to comprehensively analyze the active metabolites of S. boulardii and the metabolic differences between S. boulardii and S. cerevisiae were compared. Saccharomyces boulardii produced many bioactive metabolites, which generally showed antioxidant, antibacterial, antitumor, anti-inflammatory, and other properties. In contrast to S. cerevisiae, S. boulardii produced phenyllactic acid and 2-hydroxyisocaproic acid. There were also significant differences in their metabolic pathways. These results may be of great significance in the medical and food industries and provide a basis for understanding the metabolism of S. boulardii. It also shows that metabolomics is an effective and novel method for screening microbial functional metabolites and identifying functional differences between similar microorganisms.
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http://dx.doi.org/10.1007/s12602-022-09953-1DOI Listing
May 2022

Screening for Primary Open-Angle Glaucoma: US Preventive Services Task Force Recommendation Statement.

JAMA 2022 May;327(20):1992-1997

Tufts University School of Medicine, Boston, Massachusetts.

Importance: Glaucoma affects an estimated 2.7 million people in the US. It is the second-leading cause of irreversible blindness in the US and the leading cause of blindness in Black and Hispanic/Latino persons.

Objective: To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for glaucoma in adults.

Population: Adults 40 years or older who present in primary care and do not have signs or symptoms of open-angle glaucoma.

Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for glaucoma in adults. The benefits and harms of screening for glaucoma in adults are uncertain. More research is needed.

Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for primary open-angle glaucoma in adults. (I statement).
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http://dx.doi.org/10.1001/jama.2022.7013DOI Listing
May 2022

Effects of Ethanolic Extract of on the Pharmacokinetics of Rosuvastatin in Rats.

Drug Des Devel Ther 2022 17;16:1473-1481. Epub 2022 May 17.

Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Purpose: Wuzhi capsule (WZ) is a proprietary Chinese medicine prepared from the ethanolic extract of that is commonly used to treat liver injury. Statins are widely used in patients with hyperlipidemia, coronary heart disease, metabolic syndrome, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Co-administration of statins with WZ is possible in clinical practice. WZ has obvious inhibitory effects on the bioavailability of atorvastatin and simvastatin; however, the drug-herb interactions between WZ and rosuvastatin have not been addressed. We explored the effects of WZ on the pharmacokinetics of rosuvastatin in Sprague-Dawley rats to promote a rational use of statins.

Methods: Eighteen male rats were randomly and evenly divided into three groups: control group (gavage feeding of rosuvastatin 10 mg·kg), single dose group (gavage feeding of a single dose of WZ 150 mg·kg followed by rosuvastatin 10 mg·kg) and multiple doses group (gavage feeding of WZ 150 mg·kg for 7 days followed by rosuvastatin 10 mg·kg on the seventh day). Plasma samples were collected at different times before and after rosuvastatin administration. The other 18 female rats were tested the same way as the male rats. All samples were analyzed by a validated LC-MS/MS method, and the pharmacokinetic parameters were calculated using a non-compartmental model.

Results: In both male and female rats, there were no statistically significant differences in rosuvastatin pharmacokinetic parameters between the control group, the single dose group, and the multi-dose group.

Conclusion: Acute or long-term intake of WZ had no obvious effect on the pharmacokinetics of rosuvastatin, and therefore rosuvastatin could be used as an alternative to atorvastatin and simvastatin when WZ is clinically required in conjunction with statins. An appropriate pharmacodynamic study is needed to encourage the safe use of this combination.
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http://dx.doi.org/10.2147/DDDT.S364234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123906PMC
May 2022

Tauroursodeoxycholic acid inhibits TGF-β1-induced renal fibrosis markers in cultured renal mesangial cells by regulating endoplasmic reticulum stress.

Exp Ther Med 2022 Jun 9;23(6):432. Epub 2022 May 9.

Department of Nephrology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 201800, P.R. China.

Chronic kidney disease (CKD) has a worldwide prevalence of higher than 10% with an increasing mortality rate. As it involves the deterioration of renal function, it represents a serious risk to human health and, if left untreated, significantly lowers the quality of the patient's life. CKD is characterized by renal fibrosis. Studies have shown that transforming growth factor β1 (TGF-β1), a key driving factor of renal fibrosis, is closely related to the activation of renal fibrosis pathways such as endoplasmic reticulum stress (ERS). Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid derivative, can effectively inhibit endogenous ERS. Here, we explored the effects and actions of TUDCA on renal fibrosis by establishing a renal mesangial cell (RMC) model. The RMC was stimulated with TGF-β1, and PCR and western blotting were used to detect the expression of ERS-related chaperone proteins and fibrotic indicators. The expression of glucose-regulated protein 78 (GRP78) was silenced in RMC cells to investigate the role of GRP78 in renal fibrosis. Finally, PCR and western blotting were used to detect the effects of TUDCA on the expression of GRP78, C/EBP homologous protein (CHOP), α-smooth muscle actin (α-SMA), and fibronectin (FN) in the TGF-β1-stimulated RMCs. The results showed that TUDCA significantly downregulated TGF-β1-induced levels of GRP78, CHOP, α-SMA and FN in RMCs. In addition, downregulation of GRP78 inhibited the expression of FN and α-SMA in the RMCs. In conclusion, downregulation of GRP78 and CHOP expression is one of the mechanisms by which TUDCA inhibits TGF-β1-induced renal mesangial cell fibrosis.
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http://dx.doi.org/10.3892/etm.2022.11359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121212PMC
June 2022

Genomic characterization of two nickie-like bacteriophages that infect the kiwifruit canker phytopathogen Pseudomonas syringae pv. actinidiae.

Arch Virol 2022 May 23. Epub 2022 May 23.

School of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China.

Here, we report the genomic characterization of two siphophages, named hairong and ZY21, that infect the kiwifruit canker phytopathogen Pseudomonas syringae pv. actinidiae. The genome sequences of hairong (112,842 bp) and ZY21 (112,006 bp) were determined. Global sequence comparison showed that hairong, ZY21, and two phages of the genus Nickievirus (nickie and psageB1) are similar but are not closely related to any other known phage, and they comprise a unique phylogenetic cluster. Moreover, hairong represents a new genus related to Nickievirus. Comparative genomic analysis revealed some common features shared by the four nickie-like phages.
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http://dx.doi.org/10.1007/s00705-022-05440-8DOI Listing
May 2022

Glycosylation increases the anti-QS as well as anti-biofilm and anti-adhesion ability of the cyclo (L-Trp-L-Ser) against Pseudomonas aeruginosa.

Eur J Med Chem 2022 May 13;238:114457. Epub 2022 May 13.

Engineering Research Center of Industrial Biocatalysis, Fujian-Taiwan Science and Technology Cooperation Base of Biomedical Materials and Tissue Engineering, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Provincial Key Laboratory of Polymer Materials, College of Chemistry and Materials Science, Fujian Normal University, 32 Shangsan Road, Fuzhou, 350007, China; College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou, 362000, China. Electronic address:

Pseudomonas aeruginosa infections pose a huge threat to cystic fibrosis patients, as well as those suffering from immunodeficiency. Antimicrobial resistance, especially multi-drug resistance, due to its ability to aggregate the compact biofilm, makes it more inefficient to treat this pathogen with traditional antibiotics. Biofilm and quorum sensing (QS) have become the alternative targets for treating P. aeruginosa infections. Previously, a cyclic dipeptide cyclo(L-Trp-L-Ser) has been identified as a QS inhibitor of P. aeruginosa. On the other hand, some monosaccharides have been proved lectin-targeting behavior and to mediate biofilm formation and adhesion of P. aeruginosa. We constructed novel cyclic dipeptide-carbohydrate conjugates as a low molecular weight dual-functional QS inhibitor, which can not only enhance its anti-QS activity but also enable good anti-biofilm and anti-adhesion ability. The IC of galactosylated c(WS) on biofilm formation and glass adhesion was 1/6 and 1/4 of that of the unmodified cyclic dipeptide, respectively. And the ability to eliminate the preformed biofilm was increased 10-fold. Furthermore, the carbohydrate conjugates can increase the germicidal efficiency of clinical antibiotic azithromycin when used synergistically. Our results provide a novel scaffold for developing anti-virulence adjuvants when taken with clinical antibiotics.
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http://dx.doi.org/10.1016/j.ejmech.2022.114457DOI Listing
May 2022

Strong second order nonlinear optical properties of azulene-based porphyrin derivatives.

Phys Chem Chem Phys 2022 May 23. Epub 2022 May 23.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, Institute of Theoretical and Simulational Chemistry, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, P. R. China.

The high stability, feasible modification, and good π-conjugation of porphyrin derivatives render these porphyrin-based nanomaterials suitable as potential third order nonlinear optical (NLO) materials. Introducing an azulene in pristine porphyrins can significantly improve the second order NLO properties of the system, and this is studied in the present work using density functional theory based methods and the sum-over-states model. The relative orientation of azulene plays a determinant role in the enhancement of the static first hyperpolarizability (〈〉), , the 〈〉 per heavy atom increases from 0.31 × 10 esu to 9.78 × 10 esu. Further addition of metals (Mg and Zn) in these azulene-fused porphyrin systems leads to an even larger 〈〉 per heavy atom of 41.59 × 10 esu, much larger than that of a recently reported porphyrin derivative (26.47 × 10 esu). A novel strategy to stabilize the electronic structures as well as maintain good second order NLO responses by introducing appropriate metals into the azulene-fused porphyrins is extendable to other similar systems. Strong sum frequency generation and different frequency generations of those azulene-fused porphyrins in visible and near-infrared regions may inspire experimental exploration and related applications of azulene-based porphyrins particularly in biological nonlinear optics.
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http://dx.doi.org/10.1039/d2cp00735eDOI Listing
May 2022

Glycyrrhetinic acid restricts mitochondrial energy metabolism by targeting SHMT2.

iScience 2022 May 4;25(5):104349. Epub 2022 May 4.

National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Glycyrrhetinic acid (GA) is a natural product of licorice with mitochondria targeting properties and shows broad anticancer activities, but its targets and underlying mechanisms remain elusive. Here, we identified the mitochondrial enzyme serine hydroxymethyltransferase 2 (SHMT2) as a target of GA by using chemical proteomics. Binding to and inhibiting the activity of SHMT2 by GA were validated and . Knockout of SHMT2 or inhibiting SHMT2 with GA restricts mitochondrial energy supplies by downregulating mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid β-oxidation, and consequently suppresses cancer cell proliferation and tumor growth. Crystal structures of GA derivatives indicate that GA occupies SHMT2 folate-binding pocket and regulates SHMT2 activity. Modifications at GA carboxylic group with diamines significantly improved its anticancer potency, demonstrating GA as a decent structural template for SHMT2 inhibitor development.
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http://dx.doi.org/10.1016/j.isci.2022.104349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117551PMC
May 2022

Prediction and Diagnosis of Respiratory Disease by Combining Convolutional Neural Network and Bi-directional Long Short-Term Memory Methods.

Front Public Health 2022 4;10:881234. Epub 2022 May 4.

Department of Clinical Research Center of Infectious Diseases (Pulmonary Tuberculosis), First People's Hospital of Kashi, Kashi, China.

Objective: Based on the respiratory disease big data platform in southern Xinjiang, we established a model that predicted and diagnosed chronic obstructive pulmonary disease, bronchiectasis, pulmonary embolism and pulmonary tuberculosis, and provided assistance for primary physicians.

Methods: The method combined convolutional neural network (CNN) and long-short-term memory network (LSTM) for prediction and diagnosis of respiratory diseases. We collected the medical records of inpatients in the respiratory department, including: chief complaint, history of present illness, and chest computed tomography. Pre-processing of clinical records with "jieba" word segmentation module, and the Bidirectional Encoder Representation from Transformers (BERT) model was used to perform word vectorization on the text. The partial and total information of the fused feature set was encoded by convolutional layers, while LSTM layers decoded the encoded information.

Results: The precisions of traditional machine-learning, deep-learning methods and our proposed method were 0.6, 0.81, 0.89, and 1 scores were 0.6, 0.81, 0.88, respectively.

Conclusion: Compared with traditional machine learning and deep-learning methods that our proposed method had a significantly higher performance, and provided precise identification of respiratory disease.
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http://dx.doi.org/10.3389/fpubh.2022.881234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114643PMC
May 2022

Predicting the Stone-Free Status of Percutaneous Nephrolithotomy With the Machine Learning System: Comparative Analysis With Guy's Stone Score and the S.T.O.N.E Score System.

Front Mol Biosci 2022 4;9:880291. Epub 2022 May 4.

Zhongshan Hospital, Fudan University, Shanghai, China.

The aim of the study was to use machine learning methods (MLMs) to predict the stone-free status after percutaneous nephrolithotomy (PCNL). We compared the performance of this system with Guy's stone score and the S.T.O.N.E score system. Data from 222 patients (90 females, 41%) who underwent PCNL at our center were used. Twenty-six parameters, including individual variables, renal and stone factors, and surgical factors were used as input data for MLMs. We evaluated the efficacy of four different techniques: Lasso-logistic (LL), random forest (RF), support vector machine (SVM), and Naive Bayes. The model performance was evaluated using the area under the curve (AUC) and compared with that of Guy's stone score and the S.T.O.N.E score system. The overall stone-free rate was 50% (111/222). To predict the stone-free status, all receiver operating characteristic curves of the four MLMs were above the curve for Guy's stone score. The AUCs of LL, RF, SVM, and Naive Bayes were 0.879, 0.803, 0.818, and 0.803, respectively. These values were higher than the AUC of Guy's score system, 0.800. The accuracies of the MLMs (0.803% to 0.818%) were also superior to the S.T.O.N.E score system (0.788%). Among the MLMs, Lasso-logistic showed the most favorable AUC. Machine learning methods can predict the stone-free rate with AUCs not inferior to those of Guy's stone score and the S.T.O.N.E score system.
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http://dx.doi.org/10.3389/fmolb.2022.880291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114350PMC
May 2022

Association of On-Admission Anemia With 1-Year Mortality in Patients Hospitalized With Acute Heart Failure: Results From the HERO Study.

Front Cardiovasc Med 2022 4;9:856246. Epub 2022 May 4.

Department of Cardiology, Beijing AnZhen Hospital, National Clinical Research Centre for Cardiovascular Diseases, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine for Cardiovascular Diseases, Capital Medical University, Beijing, China.

Background: Anemia is common in patients with chronic heart failure (HF) and is associated with adverse outcomes. However, data regarding the prognostic value of on-admission anemia on mortality in patients hospitalized with acute HF were relatively limited and conflicting. This study aimed to investigate the association of on-admission anemia with 1-year mortality and evaluate whether anemia is an independent predictor of mortality in patients hospitalized with acute HF.

Methods: The present analysis included 4,244 patients hospitalized with acute HF from the HERO (Heart Failure Registry of Patient Outcomes) study. On-admission anemia was defined using the World Health Organization (WHO) criteria (hemoglobin <120 g/L in women and <130 g/L in men). Cox proportional hazards models were used to assess the association of anemia with 1-year all-cause and cardiovascular mortality.

Results: Of 4,244 patients, 2,206 (52.0%) patients had no anemia, 1,106 (26.1%) patients had mild anemia (men 110 ≤ hemoglobin < 130 g/L; women 110 ≤ hemoglobin < 120g/L), and 932 (22.0%) patients had moderate-to-severe anemia (hemoglobin < 110 g/L). After a median follow-up of 12.4 months (interquartile range: 11.9, 12.6), 867 (20.4%) patients died. Among the 742 (85.6%) deaths with confirmed causes, 664 (89.5%) were due to cardiovascular diseases. The mortality rates in patients with no anemia, mild anemia, and moderate-to-severe anemia were 16.6%, 20.4%, and 29.4%, respectively ( < 0.001). The association of anemia with increased all-cause mortality was significant in the unadjusted model (hazard ratio [HR]: 1.54, 95% confidential interval [CI]: 1.35-1.77, < 0.001), and remained statistically significant after adjustment for most potential confounders (HR: 1.20, 95%CI: 1.03-1.40, = 0.020), but no longer significant after additional adjustment for natriuretic peptides (HR: 1.02, 95%CI: 0.86-1.21, = 0.843). When considering the degree of anemia, moderate-to-severe anemia was an independent predictor of all-cause mortality after full adjustment (HR:1.26, 95%CI: 1.03-1.54, = 0.028), whereas mild anemia was not (HR: 0.84, 95%CI: 0.69-1.04, = 0.104). A similar relationship was also found between anemia and cardiovascular mortality.

Conclusions: On-admission anemia, defined by the WHO criteria, is not an independent predictor of mortality in patients hospitalized with acute HF. Moderate-to-severe anemia in patients with acute HF is independently associated with increased mortality.
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http://dx.doi.org/10.3389/fcvm.2022.856246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114434PMC
May 2022

p53 missense mutant G242A subverts natural killer cells in sheltering mouse breast cancer cells against immune rejection.

Exp Cell Res 2022 May 18:113210. Epub 2022 May 18.

School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana at Monroe, Monroe, LA, USA. Electronic address:

Cancer cells acquire immunoediting ability to evade immune surveillance and thus escape eradication. It is widely known that mutant proteins encoded from tumor suppressor TP53 exhibit gain-of-function in cancer cells, thereby promoting progression; however, how mutant p53 contributes to the sheltering of cancer cells from host anticancer immunity remains unclear. Herein, we report that murine p53 missense mutation G242A (corresponding to human G245A) suppresses the activation of host natural killer (NK) cells, thereby enabling breast cancer cells to avoid immune assault. We found that serial injection of EMT6 breast cancer cells that carry wild-type (wt) Trp53, like normal fibroblasts, promoted NK activity in mice, while SVTneg2 cells carrying Trp53 G242A mutation decreased NK cell numbers and increased CD8 T lymphocyte numbers in spleen. Innate immunity based on NK cells and CD8 T cells was reduced in p53 mutant-carrying transgenic mice (Trp53 R172H, corresponding to human R175H). Further, upon co-culture with isolated NK cells, EMT6 cells substantively activated NK cells and proliferation thereof, increasing interferon-gamma (IFN-γ) production; however, SVTneg2 cells suppressed NK cell activation. Further mechanistic study elucidated that p53 can modulate expression by cancer cells of Mult-1 and H60a, which are activating and inhibitory ligands for NKG2D receptors of NK cells, respectively, to enhance immune surveillance against cancer. Our findings demonstrate that wt p53 is requisite for NK cell-based immune recognition and elimination of cancerous cells, and perhaps more importantly, that p53 missense mutant presence in cancer cells impairs NK cell-attributable responses, thus veiling cancerous cells from host immunity and enabling cancer progression.
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http://dx.doi.org/10.1016/j.yexcr.2022.113210DOI Listing
May 2022

Acidified glycerol as a one-step efficient green extraction and preservation strategy for anthocyanin from blueberry pomace: New insights into extraction and stability protection mechanism with molecular dynamic simulation.

Food Chem 2022 May 16;390:133226. Epub 2022 May 16.

College of Biosystems Engineering and Food Science, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, China Zhejiang Key Laboratory for Agri-Food Processing, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, China Zhejiang University, Hangzhou 310058, People's Republic of China; Ningbo Research Institute, Zhejiang University, Ningbo 315100, People's Republic of China; Fuli Institute of Food Science, Hangzhou 310058, People's Republic of China. Electronic address:

In present work, green and efficient glycerol solvent system was coupled with pulse-probe ultrasonication for one-step extraction and preservation of anthocyanin from blueberry pomace. Under optimal conditions (40 min, 174 W, 18.6 mL/g, 20% of glycerol fraction), extraction yield was 23.07 ± 0.09 mg C3GE/g DW. The extracted anthocyanins were characterized by UPLC-Triple-TOF/MS and 10 anthocyanins compounds were tentatively identified. Stability of anthocyanins influenced by solvents were evaluated in varying temperature, pH and light exposure conditions, demonstrating higher stability of anthocyanins in glycerol solvent system than methanol one. Furthermore, mechanism of high efficiency extraction and stability of anthocyanin using glycerol were investigated by quantum chemical calculation with molecular dynamic simulation. Larger solvent accessible surface area (127.16 nm), hydrogen bonds number (228.16) and hydrogen bonds lifetime (4.35 ps), and lower intermolecular interaction energy (-1080.48 kJ/mol) between anthocyanin and glycerol were responsible for better extraction and preservation of anthocyanins using glycerol system.
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http://dx.doi.org/10.1016/j.foodchem.2022.133226DOI Listing
May 2022

Acupuncture for Pain and Function in Patients with Nonspecific Low Back Pain: Study Protocol for an Up-to-Date Systematic Review and Meta-Analysis.

J Pain Res 2022 10;15:1379-1387. Epub 2022 May 10.

Teaching and Research Section of Clinical Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.

Aim: To assess the pain and function of acupuncture in patients with nonspecific low back pain (NSLBP).

Design: This is a study protocol for an upcoming, updated systematic review and meta-analysis. We have registered on the PROSPERO platform, and the registration number is CRD42020149647.

Methods: We will identify studies in seven English databases, including Web of Science, Cochrane Library, CINAHL, Physiotherapy Evidence Database, Medline, Embase, and Scopus, and in four Chinese databases, including China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), Wanfang Database, and VIP database. We will also manually search key journals about acupuncture, the references of identified relevant trials, and the Clinical Trials Registry Platform. Different search strategies of Medical Subject Headings (MeSH) and non-MeSH terms will be applied alone or integrated. We will evaluate methodological quality by adopting Cochrane's risk of bias criteria and perform a meta-analysis using RevMan V.5.4 software.

Results: This study's results will be reported according to the PRISMA checklist and presented at an authoritative scientific conference or an authoritative scientific journal.
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http://dx.doi.org/10.2147/JPR.S362980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112338PMC
May 2022

MiR-320b and miR-320d as Biomarkers to Predict and Participate in the Formation of Platinum Resistance in Ovarian Cancer Patients.

Front Oncol 2022 3;12:881496. Epub 2022 May 3.

Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, China.

Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients.
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http://dx.doi.org/10.3389/fonc.2022.881496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110861PMC
May 2022

TRPC5 deletion in the central amygdala antagonizes high-fat diet-induced obesity by increasing sympathetic innervation.

Int J Obes (Lond) 2022 May 20. Epub 2022 May 20.

Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, 400042, China.

Transient receptor potential channel 5 (TRPC5) is predominantly distributed in the brain, especially in the central amygdala (CeA), which is closely associated with pain and addiction. Although mounting evidence indicates that the CeA is related to energy homeostasis, the possible regulatory effect of TRPC5 in the CeA on metabolism remains unclear. Here, we reported that the expression of TRPC5 in the CeA of mice was increased under a high-fat diet (HFD). Specifically, the deleted TRPC5 protein in the CeA of mice using adeno-associated virus resisted HFD-induced weight gain, accompanied by increased food intake. Furthermore, the energy expenditure of CeA-specific TRPC5 deletion mice (TRPC5 KO) was elevated due to augmented white adipose tissue (WAT) browning and brown adipose tissue (BAT) activity. Mechanistically, deficiency of TRPC5 in the CeA boosted nonshivering thermogenesis under cold stimulation by stimulating sympathetic nerves, as the β3-adrenoceptor (Adrb3) antagonist SR59230A blocked the effect of TRPC5 KO on this process. In summary, TRPC5 deletion in the CeA alleviated the metabolic deterioration of mice fed a HFD, and these phenotypic improvements were correlated with the increased sympathetic distribution and activity of adipose tissue.
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http://dx.doi.org/10.1038/s41366-022-01151-xDOI Listing
May 2022

Plasma Drug Concentration of Propranolol and Genetic Study in Chinese Han Patients With Infantile Haemangioma.

Front Pediatr 2022 2;10:849496. Epub 2022 May 2.

Department of Dermatology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Background And Purpose: This study was conducted to explore the plasma drug concentration of propranolol in Chinese Han patients with infantile haemangioma (IH) and the influencing factors, as well as the relationship among plasma drug concentrations of propranolol, β1-AR mutation and CYP2D6 188C>T, efficacy, and safety.

Experimental Approach: From January 2018 to April 2019, 140 patients with IH who were admitted to the hospital for oral propranolol and agreed to have their plasma concentration of propranolol tested, including 112 patients with β1-AR and CYP2D6 gene tested.

Key Results And Conclusions And Implications: The mean peak blood levels of propranolol, 4-hydroxypropranolol (4-OH-P), and N-deisopropylpropranolol (NDP) were 60.35 ± 37.90, 1.90 ± 2.37, and 0.24 ± 0.18 ng/ml, respectively. The mean trough blood levels of propranolol, 4-OH-P, and NDP were 24.98 ± 17.68, 0.45 ± 0.52, and 0.05±0.05 ng/ml, respectively. The higher the dose of propranolol, the higher the plasma concentration of propranolol ( = 0.031). The plasma concentration of propranolol was not related to the treatment efficacy.
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http://dx.doi.org/10.3389/fped.2022.849496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108385PMC
May 2022

Lipolysis-Stimulated Lipoprotein Receptor Impairs Hepatocellular Carcinoma and Inhibits the Oncogenic Activity of YAP1 PPPY Motif.

Front Oncol 2022 2;12:896412. Epub 2022 May 2.

Department of General Surgery & Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy, Shenzhen, China.

Purpose: Lipolysis-stimulated lipoprotein receptor (LSR) is a type I single-pass transmembrane protein which is mainly expressed in the liver. In this study, we investigated if and how LSR is involved in the carcinogenesis of hepatocellular carcinoma (HCC).

Experimental Design: To evaluate if LSR was abnormally expressed in human HCC tissues, and how its expression was associated with the survival probability of patients, we obtained data from Gene Expression Omnibus and The Cancer Genome Atlas Program. To investigate if and how LSR regulates tumor growth, we knocked down and overexpressed LSR in human HCC cell lines. In addition, to evaluate the interaction between LSR and yes-associated protein1 (YAP1), we mutated LSR at PPPY motif, a binding site of YAP1.

Results: Totally, 454 patients were enrolled in the present study, and high expression of LSR significantly decreased the probability of death. Knockdown of LSR significantly increased the expansion of HCC cells and significantly promoted tumor growth. In addition, downregulation of LSR increased the nuclear accumulation and transcriptional function of YAP1. Conversely, overexpression of LSR impairs this function of YAP1 and phosphorylates YAP1 at serine 127. Of note, mutation of LSR at the PPPY motif could block the interaction between LSR and YAP1, and restore the transcriptional ability of YAP1.

Conclusions: The present study suggests that LSR binds to YAP1 the PPPY motif. Thus, LSR increases the phosphorylation of YAP1 and impairs the growth of HCC. This highlights that targeting LSR might be a promising therapeutic strategy for HCC.
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http://dx.doi.org/10.3389/fonc.2022.896412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108500PMC
May 2022

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia.

Support Care Cancer 2022 May 19. Epub 2022 May 19.

Department of Hematology, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Purpose: The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine.

Methods: A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented.

Results: Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications.

Conclusion: Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections.
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http://dx.doi.org/10.1007/s00520-022-07126-yDOI Listing
May 2022

Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior, and hypothalamic gene expression.

Cell Rep 2022 May;39(7):110835

School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, Scotland, UK; Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PRC; CAS Center of Excellence in Animal Evolution and Genetics, Kunming, PRC. Electronic address:

Caloric restriction is a robust intervention to increase lifespan. Giving less food (calorie restriction [CR]) or allowing free access to a diluted diet with indigestible components (calorie dilution [CD]) are two methods to impose restriction. CD does not generate the same lifespan effect as CR. We compare responses of C57BL/6 mice with equivalent levels of CR and CD. The two groups have different responses in fat loss, circulating hormones, and metabolic rate. CR mice are hungrier, as assessed by behavioral assays. Although gene expression of Npy, Agrp, and Pomc do not differ between CR and CD groups, CR mice had a distinctive hypothalamic gene-expression profile with many genes related to starvation upregulated relative to CD. While both result in lower calorie intake, CR and CD are not equivalent procedures. Increased hunger under CR supports the hypothesis that hunger signaling is a key process mediating the benefits of CR.
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http://dx.doi.org/10.1016/j.celrep.2022.110835DOI Listing
May 2022

Phytochemistry, synthesis, analytical methods, pharmacological activity, and pharmacokinetics of loganin: A comprehensive review.

Phytother Res 2022 May 18. Epub 2022 May 18.

Department of Pharmacy & Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.
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http://dx.doi.org/10.1002/ptr.7347DOI Listing
May 2022

Study Design and Baseline Characteristics of Patients with T2DM in the Post-marketing Safety Study of Dulaglutide in China (TRUST-CHN).

Diabetes Ther 2022 May 18. Epub 2022 May 18.

Eli Lilly Suzhou Pharmaceutical Co. Ltd, Shanghai, China.

Background: TRUST-CHN is a prospective, post-marketing safety study in patients with type 2 diabetes mellitus (T2DM) in China to evaluate the safety and effectiveness of dulaglutide in real-world clinical practice. We report here the study design and baseline characteristics of enrolled patients.

Methods: The study design was described, and baseline data were analyzed, including demographic characteristics, T2DM duration, comorbidities, dulaglutide treatment patterns, and concomitant medications.

Results: For the present analysis of this ongoing study, data were collected from January 2020 to November 2021. A total of 3313 patients were enrolled, of whom 3294 patients were included in the safety analysis. In total, 1047 patients had a prior history of dulaglutide use before being enrolled in the study. The mean (standard deviation [SD]) age of study subjects was 50.1 (13.2) years, 85.1% were aged < 65 years; 67.9% were male, and 35.9% had an education of university level or higher. Mean (SD) duration of T2DM was 6.4 (6.7) years. Baseline mean (SD) glycated hemoglobin was 8.8% (2.2%), and mean (SD) body mass index was 28.1 (4.1) kg/m. A total of 2867 (87%) patients had at least one comorbidity, the most frequently reported of which were overweight/obesity (87.1%), hyperlipidemia (50.5%), hypertension (47.9%), diabetic neuropathy (18.9%), and coronary artery disease (15.7%). Almost all (99.7%) patients were treated with 1.5 mg dulaglutide; at baseline, 24.8% were treated with this medication as monotherapy and 75.2% in combination therapy with other medications, including metformin (42.3%), sodium glucose co-transporter2 inhibitor (26.7%), insulin (18.3%), α-glucosidase inhibitor (13.1%), sulfonylurea (5.3%), dipeptidyl peptidase 4 inhibitor (4.4%), glucagon-like peptide 1 receptor agonist (2.7%), and thiazolidinedione (2.4%).

Conclusion: The present analysis revealed real-world baseline characteristics of patients with T2DM in China who use dulaglutide enrolled in TRUST-CHN. These data will enable further exploration of the characteristics of patients with T2DM in China and provide an insight on the current use of dulaglutide in clinical practice.
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http://dx.doi.org/10.1007/s13300-022-01268-2DOI Listing
May 2022
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