Publications by authors named "Cheng Hu"

538 Publications

Previously Unrecognized Nonreproducible Antibody-Probe Interactions.

Anal Chem 2022 Jan 19. Epub 2022 Jan 19.

Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.

Antibody-antigen (Ab-Ag) interactions are canonically described by a model that exclusively accommodates noninteraction (0) or reproducible interaction (RI) states, yet this model is inadequate to explain often-encountered nonreproducible signals. Here, by monitoring diverse experimental systems using a peptide-protein hybrid microarray, we observed that Ab-probe interactions comprise a substantial proportion of nonreproducible antibody-based results. This enabled our discovery and capacity to reliably identify nonreproducible Ab-probe interactions (NRIs), as well as our development of a powerful explanatory model ("0-NRI-RI-Hook four-state model") that is mAb concentration-dependent, regardless of specificity, which ultimately shows that both nonspecific interactions and NRIs are not predictable yet certain to happen. Our discoveries challenge the centrality of Ab-Ag interaction specificity data in serology and immunology.
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http://dx.doi.org/10.1021/acs.analchem.1c03264DOI Listing
January 2022

Ginseng in vascular dysfunction: A review of therapeutic potentials and molecular mechanisms.

Phytother Res 2022 Jan 13. Epub 2022 Jan 13.

Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.

Vascular dysfunction can lead to a variety of fatal diseases, including cardiovascular and cerebrovascular diseases, metabolic syndrome, and cancer. Although a large number of studies have reported the therapeutic effects of natural compounds on vascular-related diseases, ginseng is still the focus of research. Ginseng and its active substances have bioactive effects against different diseases with vascular dysfunction. In this review, we summarized the key molecular mechanisms and signaling pathways of ginseng, its different active ingredients or formula in the prevention and treatment of vascular-related diseases, including cardiac-cerebral vascular diseases, hypertension, diabetes complications, and cancer. Moreover, the bidirectional roles of ginseng in promoting or inhibiting angiogenesis have been highlighted. We systematically teased out the relationship between ginseng and vascular dysfunction, which could provide a basis for the clinical application of ginseng in the future.
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http://dx.doi.org/10.1002/ptr.7369DOI Listing
January 2022

An umpolung strategy for rapid access to thermally activated delayed fluorescence (TADF) materials based on phenazine.

Chem Commun (Camb) 2022 Jan 12. Epub 2022 Jan 12.

Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.

Herein, Ag(I)-promoted regioselective intramolecular radical nucleophilic addition/rearrangement of 2-aryl diazaboroles has been accomplished for the first time to construct phenazine structures. This protocol is an umpolung strategy based on the classical electrophilic mechanism, and therefore, a reversed regioselectivity was observed, which provides an opportunity to prepare sterically hindered phenazines. The resulting thermally activated delayed fluorescence (TADF) materials based on phenazine exhibit emission bands from green to red with high quantum yields and moderate fluorescence lifetimes as solid films.
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http://dx.doi.org/10.1039/d1cc06705bDOI Listing
January 2022

Correction to: Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry.

J Transl Med 2022 Jan 10;20(1):24. Epub 2022 Jan 10.

Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China.

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http://dx.doi.org/10.1186/s12967-021-03223-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744349PMC
January 2022

Dissolving microneedle-encapsulated drug-loaded nanoparticles and recombinant humanized collagen type III for the treatment of chronic wound anti-inflammation and enhanced cell proliferation and angiogenesis.

Nanoscale 2022 Jan 10. Epub 2022 Jan 10.

National Engineering Research Center for Biomaterials, Chuanda-Jinbo Joint Research Center, Sichuan University, Chengdu, 610064, China.

Nowadays, diabetic chronic wounds impose a heavy burden on patients and the medical system. Persistent inflammation and poor tissue remodeling severely limit the healing of chronic wounds. For these issues, the first recombinant humanized collagen type III (rhCol III) and naproxen (Nap) loaded poly(lactic--glycolic acid) (PLGA) nanoparticle incorporated hyaluronic acid (HA) microneedle (MN) was fabricated for diabetic chronic wound therapy. As the tailored rhCol III was synthesized based on the Gly483-Pro512 segment, which contained the highly adhesive fragments (GER, GEK) in the human collagen type III sequence, it possessed strong cell adhesion. The mechanical strength of the prepared MN was enough to overcome the tissue barrier of necrosis/hyperkeratosis in a minimally invasive way after being applied in wounds. Subsequently, rhCol III and [email protected] nanoparticles were rapidly released to the wound site within a few minutes. The prepared MN possessed favourable biocompatibility and could effectively facilitate the proliferation and migration of fibroblasts and endothelial cells. Furthermore, the regenerative efficacy of the MN was evaluated using the diabetic rat full-thickness skin wound model. These results illustrated that the prepared MN could accelerate wound closure by reducing the inflammatory response and enhancing angiogenesis or collagen deposition, indicating their significant application value in wound dressings for chronic wound repair.
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http://dx.doi.org/10.1039/d1nr07708bDOI Listing
January 2022

Advances With Non-coding RNAs in Neuropathic Pain.

Front Neurosci 2021 23;15:760936. Epub 2021 Dec 23.

Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

Neuropathic pain (NP) is one of the most common types of clinical pain. The common causes of this syndrome include injury to the central or peripheral nervous systems and pathological changes. NP is characterized by spontaneous pain, hyperalgesia, abnormal pain, and paresthesia. Because of its diverse etiology, the pathogenesis of NP has not been fully elucidated and has become one of the most challenging problems in clinical medicine. This kind of pain is extremely resistant to conventional treatment and is accompanied by serious complications. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), contribute to diverse biological processes by regulating the expression of various mRNAs involved in pain-related pathways, at the posttranscriptional level. Abnormal regulation of ncRNAs is closely related to the occurrence and development of NP. In this review, we summarize the current state of understanding of the roles of different ncRNAs in the development of NP. Understanding these mechanisms can help develop novel therapeutic strategies to prevent or treat chronic pain.
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http://dx.doi.org/10.3389/fnins.2021.760936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733285PMC
December 2021

In-situ twistable bilayer graphene.

Sci Rep 2022 Jan 7;12(1):204. Epub 2022 Jan 7.

Key Laboratory of Artificial Structures and Quantum Control (Ministry of Education), Shenyang National Laboratory for Materials Science, School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240, China.

The electrical and optical properties of twisted bilayer graphene (tBLG) depend sensitively on the twist angle. To study the angle dependent properties of the tBLG, currently it is required fabrication of a large number of samples with systematically varied twist angles. Here, we demonstrate the construction of in-situ twistable bilayer graphene, in which the twist angle of the two graphene monolayers can be in-situ tuned continuously in a large range with high precision. The controlled tuning of the twist angle is confirmed by a combination of real-space and spectroscopic characterizations, including atomic force microscopy (AFM) identification of crystal lattice orientation, scanning near-field optical microscopy (SNOM) imaging of superlattice domain walls, and resonant Raman spectroscopy of the largely enhanced G-mode. The developed in-situ twistable homostructure devices enable systematic investigation of the twist angle effects in a single device, thus could largely advance the research of twistronics.
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http://dx.doi.org/10.1038/s41598-021-04030-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741971PMC
January 2022

Bifurcated Topological Optimization for IVIM.

Front Neurosci 2021 15;15:779025. Epub 2021 Dec 15.

Intelligent Systems Engineering, Indiana University, Bloomington, IN, United States.

In this work, we shed light on the issue of estimating Intravoxel Incoherent Motion (IVIM) for diffusion and perfusion estimation by characterizing the objective function using simplicial homology tools. We provide a robust solution via topological optimization of this model so that the estimates are more reliable and accurate. Estimating the tissue microstructure from diffusion MRI is in itself an ill-posed and a non-linear inverse problem. Using variable projection functional (VarPro) to fit the standard bi-exponential IVIM model we perform the optimization using simplicial homology based global optimization to better understand the topology of objective function surface. We theoretically show how the proposed methodology can recover the model parameters more accurately and consistently by casting it in a reduced subspace given by VarPro. Additionally we demonstrate that the IVIM model parameters cannot be accurately reconstructed using conventional numerical optimization methods due to the presence of infinite solutions in subspaces. The proposed method helps uncover multiple global minima by analyzing the local geometry of the model enabling the generation of reliable estimates of model parameters.
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http://dx.doi.org/10.3389/fnins.2021.779025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714828PMC
December 2021

Effect of chlorination on the characteristics of effluent organic matter and the phototransformation of sulfamethoxazole in secondary wastewater.

Chemosphere 2021 Dec 28:133193. Epub 2021 Dec 28.

Co-Innovation Center for Sustainable Forestry in Southern China, College of Biology and the Environment, Nanjing Forestry University, Longpan Road 159, Nanjing, 210037, China.

Chlorination is the most common disinfection technology used to treat wastewater effluent discharged into receiving aquatic environments. Effluent organic matter (EfOM) abundant in wastewater is a well-known photosensitizer and it greatly affects phototransformations of antibiotics in water. However, effects of chlorination on the characteristics and photochemical properties of EfOM have not been studied in sufficient detail. This paper investigated effects of chlorination on the characteristics of EfOM, and its impact on the phototransformation of sulfamethoxazaole (SMX). Correlations between the EfOM characteristics and steady-state concentrations of reactive intermediates (RI) formed in the system were established. Chlorination was shown to preferentially remove the aromatic protein-like substances in EfOM, and the incorporation of chlorine into followed by the cleavage of the aromatic rings in EfOM molecules led to the formation of low molecular aliphatic organic matter. Both unaltered and chlorinated EfOM promoted the photodegradation of SMX whose rate constant in the wastewater was 1.32-1.65 times higher than that in pH 8 phosphate buffer. However, the rate of SMX photodegradation decreased at higher chlorination concentration. The photodegradation of SMX was found to proceed through direct photolysis and oxidation by the RIs generated from EfOM and the self-sensitization of SMX. The steady-state concentrations of ·OH, O and EfOM* were 2.15-5.50 × 10, 0.42-1.51 × 10, and 2.54-5.82 × 10 M in unaltered and chlorinated wastewater. The steady-state concentrations of ·OH were well correlated with the removal of the fluorescence regional integration (ΔFRI) for humic-like and soluble microbial products (SMPs), while the photodegradation rate constant of SMX and the steady-state concentration of O and EfOM* showed good correlations with ΔFRI for tryptophan and fulvic-like substances. Six transformation products (TPs) of SMX were identified. These findings provide new insights into the photochemical properties of chlorinated EfOM in the aquatic environments and its roles in the degradation of antibiotics and other trace-level pharmaceuticals.
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http://dx.doi.org/10.1016/j.chemosphere.2021.133193DOI Listing
December 2021

Government environmental control measures on CO emission during the 2014 Youth Olympic Games in Nanjing: Perspectives from a top-down approach.

J Environ Sci (China) 2022 Mar 25;113:165-178. Epub 2021 Jun 25.

College of Biology and the Environment, Joint Center for sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China.

Strict air pollution control measures were conducted during the Youth Olympic Games (YOG) period at Nanjing city and surrounding areas in August 2014. This event provides a unique chance to evaluate the effect of government control measures on regional atmospheric pollution and greenhouse gas emissions. Many previous studies have observed significant reductions of atmospheric pollution species and improvement in air quality, while no study has quantified its synergism on anthropogenic CO emissions, which can be co-reduced with air pollutants. To better understand to what extent these pollution control measures have reduced anthropogenic CO emissions, we conducted atmospheric CO measurements at the suburban site in Nanjing city from 1 July to 30 September 2014 and 1 August to 31 August 2015, obvious decrease in atmospheric CO was observed between YOG and the rest period. By coupling the a priori emission inventory with atmospheric transport model, we applied the scale factor Bayesian inversion approach to derive the posteriori CO emissions in YOG period and regular period. Results indicate CO emissions from power industry decreased by 45%, and other categories also decreased by 16% for manufacturing combusting, and 37% for non-metallic mineral production. Monthly total anthropogenic CO emissions were 9.8 (±3.6) × 10 kg/month CO for regular period and decreased to 6.2 (±1.9) × 10 kg/month during the YOG period in Nanjing city, with a 36.7% reduction. When scaling up to whole Jiangsu Province, anthropogenic CO emissions were 7.1 (±2.4) × 10 kg/month CO for regular period and decreased to 4.4 (±1.2) × 10 kg/month CO during the YOG period, yielding a 38.0% reduction.
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http://dx.doi.org/10.1016/j.jes.2021.04.016DOI Listing
March 2022

Hepatic P38 Activation Modulates Systemic Metabolism Through Fgf21-Mediated Interorgan Communication.

Diabetes 2021 Oct 21. Epub 2021 Oct 21.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of 1CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Sciences; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in a hepatic p38α- and FGF21-dependent manner. Mechanistically, through increasing the FGF21 production from liver, hepatic p38 activation increases the influx of fatty acids from adipose tissue to liver, leading to hepatic ectopic lipid accumulation and insulin resistance. Although hepatic p38 activation exhibits favorable effects in peripheral tissues, it impairs the hepatic FGF21 action by facilitating the ubiquitination and degradation of FGF21 receptor cofactor β-Klotho. Consistently, we show that p38 phosphorylation and FGF21 expffression are increased, β-Klotho protein levels are decreased in the fatty liver of either mice or patients. In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38α, FGF21, and β-Klotho in the pathogenesis of nonalcoholic fatty liver disease.
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http://dx.doi.org/10.2337/db21-0240DOI Listing
October 2021

Functional Characterization of a Novel Heterozygous Mutation in the Glucokinase Gene That Causes MODY2 in Chinese Pedigrees.

Front Endocrinol (Lausanne) 2021 9;12:803992. Epub 2021 Dec 9.

Department of Endocrinology, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Glucokinase (GCK) plays a central role in glucose regulation. The heterozygous mutations of can cause a monogenic form of diabetes, maturity-onset diabetes of the young (MODY) directly. In our study, we aimed to explore the mechanism of the novel mutation p.Ala259Thr leading to glucokinase deficiency and hyperglycemia.

Methods: Thirty early-onset diabetes pedigrees were referred to whole exome sequencing for novel mutations identification. Purified wild-type and mutant GCK proteins were obtained from systems and then subjected to the kinetic and thermal stability analysis to test the effects on GCK activity.

Results: One novel missense mutation p.Ala259Thr was identified and co-segregated with diabetes in a Chinese MODY2 pedigree. The kinetic analysis showed that this mutation result in a decreased affinity and catalytic capability for glucose. The thermal stability analysis also indicated that the mutant protein presented dramatically decreased activity at the same temperature.

Conclusion: Our study firstly identified a novel MODY2 mutation p.Ala259Thr in Chinese diabetes pedigrees. The kinetic and thermal stability analysis confirmed that this mutation caused hyperglycemia through severely damaging the enzyme activities and protein stability.
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http://dx.doi.org/10.3389/fendo.2021.803992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695754PMC
December 2021

Hierarchical porous biochars with controlled pore structures derived from co-pyrolysis of potassium/calcium carbonate with cotton straw for efficient sorption of diethyl phthalate from aqueous solution.

Bioresour Technol 2021 Dec 23;346:126604. Epub 2021 Dec 23.

Co-Innovation Center for the Sustainable Forestry in Southern China, College of Biology and the Environment, Nanjing Forestry University, Nanjing 210037, PR China; National Positioning Observation Station of Hung-tse Lake Wetland Ecosystem, Huaian 223100, PR China.

A one-pot co-pyrolysis of potassium/calcium carbonate with biowaste-derived hydrochar strategy was proposed to prepare hierarchical porous biochars (HPBs) for the first time. The pore structure, especially the pore size distribution, could be designed by adjusting the mass ratios of different carbonates. HPBs were hydrophobic, nitrogen doped, graphitized, and contained surface functional groups. HPBs showed unexpected sorption quantity for diethyl phthalate (DEP) that reached 657 mg g, which much higher than that of the reported sorbents. The sorption was multilayered and had multiple action modes, and was limited by the chemical sorption and the sorption quantity was dominated by the physical sorption. Lewis acid-base interaction, π-π stacking interaction, hydrogen bonding interaction, partitioning and pore filling were the potential sorption mechanisms. This work proposed a simple, environmentally friendly and low-cost method to convert biowaste into advanced HPBs and confirmed that produced HPBs represent ideal sorbents for the removal of organic pollutants.
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http://dx.doi.org/10.1016/j.biortech.2021.126604DOI Listing
December 2021

Growth differentiation factor 15 is an early predictor for persistent organ failure and mortality in acute pancreatitis.

Pancreatology 2021 Dec 11. Epub 2021 Dec 11.

From Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Objectives: Early prediction of persistent organ failure (POF) is crucial for patients with acute pancreatitis (AP). Growth differentiation factor 15 (GDF15), also known as macrophage inhibitory cytokine 1 (MIC-1), is associated with inflammatory responses. We investigated changes in plasma GDF15 and assessed its predictive value in AP.

Methods: The study included 290 consecutive patients with AP admitted within 36 h after symptoms onset. Clinical data obtained during hospitalization were collected. Plasma GDF15 levels were determined using enzyme-linked immunosorbent assays. The predictive value of GDF15 for POF was analyzed.

Results: There were 105 mild, 111 moderately severe, and 74 severe AP patients. Plasma GDF15 peak level were measured on admission, and significantly declined on the 3rd and 7th day. Admission GDF15 predicted POF and mortality with areas under the curve (AUC) of 0.847 (95% confidence interval [CI] 0.798-0.895) and 0.934 (95% CI 0.887-0.980), respectively. Admission GDF15, Bedside Index of Severity in Acute Pancreatitis, and hematocrit were independent factors for POF by univariate and multivariate logistic regression, and the nomogram built on these variables showed good performance (optimism-corrected c-statistic = 0.921). The combined predictive model increased the POF accuracy with an AUC 0.925 (95% CI 0.894-0.956), a net reclassification improvement of 0.3024 (95% CI: 0.1482-0.4565, P < 0.001), and an integrated discrimination index of 0.11 (95% CI 0.0497-0.1703; P < 0.001).

Conclusions: Plasma GDF15 measured within 48 h of symptom onset could help predict POF and mortality in AP patients.
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http://dx.doi.org/10.1016/j.pan.2021.12.001DOI Listing
December 2021

Fixed-Time Synchronization Control of Delayed Dynamical Complex Networks.

Entropy (Basel) 2021 Nov 30;23(12). Epub 2021 Nov 30.

College of Mathematics and System Sciences, Xinjiang University, Urumqi 830046, China.

Fixed-time synchronization problem for delayed dynamical complex networks is explored in this paper. Compared with some correspondingly existed results, a few new results are obtained to guarantee fixed-time synchronization of delayed dynamical networks model. Moreover, by designing adaptive controller and discontinuous feedback controller, fixed-time synchronization can be realized through regulating the main control parameter. Additionally, a new theorem for fixed-time synchronization is used to reduce the conservatism of the existing work in terms of conditions and the estimate of synchronization time. In particular, we obtain some fixed-time synchronization criteria for a type of coupled delayed neural networks. Finally, the analysis and comparison of the proposed controllers are given to demonstrate the validness of the derived results from one numerical example.
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http://dx.doi.org/10.3390/e23121610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700179PMC
November 2021

The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis.

Comput Struct Biotechnol J 2021 26;19:6375-6385. Epub 2021 Nov 26.

Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China.

Chronic pancreatitis (CP) is characterized by irreversible fibro-inflammatory changes induced by pancreatic stellate cell (PSC). Unresolved or recurrent injury causes dysregulation of biological process following AP, which would cause CP. Here, we systematically identify genes whose expressions are unique to PSC by comparing transcriptome profiles among total pancreas, pancreatic stellate, acinar, islet and immune cells. We then identified candidate genes and correlated them with the pancreatic disease continuum by performing intersection analysis among total PSC and activated PSC genes, and genes persistently differentially expressed during acute pancreatitis (AP) recovery. Last, we examined the association between candidate genes and AP, and substantiated their potential as biomarkers in experimental AP and recurrent AP (RAP) models. A total of 68 genes were identified as highly and uniquely expressed in PSC. The PSC signatures were highly enriched with extracellular matrix remodeling genes and were significantly enriched in AP pancreas compared to healthy control tissues. Among PSC signature genes that comprised a fibrotic phenotype, 10 were persistently differentially expressed during AP recovery. SPARC was determined as a candidate marker for the pancreatic disease continuum, which was not only persistently differentially expressed even five days after AP injury, but also highly expressed in two clinical datasets of CP. Sparc was also validated as highly elevated in RAP compared to AP mice. This work highlights the unique transcriptional profiles of PSC. These PSC signatures' expression may help to identify patients with high risk of AP progression to CP.
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http://dx.doi.org/10.1016/j.csbj.2021.11.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649580PMC
November 2021

Correction: Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds.

J Mater Chem B 2022 Jan 5;10(2):328. Epub 2022 Jan 5.

National Engineering Research Center for Biomaterials, Chuanda-Jinbo Joint Research Center, Sichuan University, Chengdu 610064, People's Republic of China.

Correction for 'Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds' by Cheng Hu , , 2021, , 9684-9699, DOI: 10.1039/D1TB02170B.
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http://dx.doi.org/10.1039/d1tb90196fDOI Listing
January 2022

Fixed/Preassigned-time synchronization of quaternion-valued neural networks via pure power-law control.

Neural Netw 2022 Feb 1;146:341-349. Epub 2021 Dec 1.

College of Mathematics and System Sciences, Xinjiang University, Urumqi 830046, China. Electronic address:

The fixed-time synchronization and preassigned-time synchronization of quaternion-valued neural networks are concerned in this article. By developing fixed-time stability and proposing a pure power-law control scheme, some simple conditions are obtained to realize fixed-time synchronization of quaternion-valued neural networks and the upper bound of the synchronized time is provided. Furthermore, the preassigned-time synchronization of quaternion-valued neural networks is investigated based on pure power-law control design, where the synchronization time is preassigned in advance and the control gains are finite. Note that the designed controllers in this paper are the pure power-law forms, which are simpler and more effective compared with the traditional design composed of the linear part and power-law part. Eventually, an example is given to illustrate the feasibility and validity of the results obtained.
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http://dx.doi.org/10.1016/j.neunet.2021.11.023DOI Listing
February 2022

[Transcutaneous electrical acupoint stimulation promotes general anesthesia recovery in patients undergoing gastrointestinal surgery].

Zhen Ci Yan Jiu 2021 Nov;46(11):963-6

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China.

Objective: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the recovery of patients undergoing gastrointestinal surgery under general anesthesia.

Methods: Sixty patients (ASA Ⅱ-Ⅲ) selected for scheduled gastrointestinal surgery were randomly divided into control group and TEAS group (=30 cases per group). Patients in the two groups received general anesthesia, and those of the TEAS group also received TEAS for 30 min (8-12 mA) immediately after surgery. The changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) before anesthesia, before acupoint stimulation, before extubation, immediately after extubation, 10 and 30 min after extubation were recorded. The recovery time of spontaneous breathing, extubation time, VAS scores and Bruggman comfort scale (BCS) scores at the time of discharging from postanesthesia care unit (PACU) were recorded.

Results: Compared with the control group, the recovery time of spontaneous breathing and extubation time were significantly shorter (<0.05), the VAS score was significantly lower (<0.05), and the BCS score significantly increased in the TEAS group (<0.05). There were no significant differences between two groups in the levels of SBP, DBP and HR at each time point (>0.05).

Conclusion: TEAS can accelerate the gastrointestinal surgery patients' recovery from general anesthesia, enhance the postoperative analgesic effect, improve patients' discomfort, has less adverse reactions, and is thus conducive to promote the postoperative rehabilitation.
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http://dx.doi.org/10.13702/j.1000-0607.201152DOI Listing
November 2021

Metabolic targeting of cancer by a ubiquinone uncompetitive inhibitor of mitochondrial complex I.

Cell Chem Biol 2021 Nov 23. Epub 2021 Nov 23.

State Key Laboratory of Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiang'An South Road, Xiamen, China; MGZ Medical Genetics Center Munich, 80335 Munich, Germany; Department of Internal Medicine II, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany. Electronic address:

SMIP004-7 is a small molecule inhibitor of mitochondrial respiration with selective in vivo anti-cancer activity through an as-yet unknown molecular target. We demonstrate here that SMIP004-7 targets drug-resistant cancer cells with stem-like features by inhibiting mitochondrial respiration complex I (NADH:ubiquinone oxidoreductase, complex I [CI]). Instead of affecting the quinone-binding site targeted by most CI inhibitors, SMIP004-7 and its cytochrome P450-dependent activated metabolite(s) have an uncompetitive mechanism of inhibition involving a distinct N-terminal region of catalytic subunit NDUFS2 that leads to rapid disassembly of CI. SMIP004-7 and an improved chemical analog selectively engage NDUFS2 in vivo to inhibit the growth of triple-negative breast cancer transplants, a response mediated at least in part by boosting CD4 and CD8 T cell-mediated immune surveillance. Thus, SMIP004-7 defines an emerging class of ubiquinone uncompetitive CI inhibitors for cell autonomous and microenvironmental metabolic targeting of mitochondrial respiration in cancer.
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http://dx.doi.org/10.1016/j.chembiol.2021.11.002DOI Listing
November 2021

Non-Local Electrostatic Gating Effect in Graphene Revealed by Infrared Nano-Imaging.

Small 2021 Nov 27:e2105687. Epub 2021 Nov 27.

Key Laboratory of Artificial Structures and Quantum Control (Ministry of Education), Shenyang National Laboratory for Materials Science, School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240, China.

Electrostatic gating lies in the heart of field effect transistor (FET) devices and modern integrated circuits. To achieve efficient gate tunability, the gate electrode has to be placed very close to the conduction channel, typically a few nanometers. Remote control of a FET device through a gate electrode located far away is highly desirable, because it not only reduces the complexity of device fabrication, but also enables the design of novel devices with new functionalities. Here, a non-local electrostatic gating effect in graphene devices using scanning near-field optical microscopy (SNOM)-a technique that can probe local charge density in graphene-is reported. Remarkably, the charge density of the graphene region tens of micrometers away from a local gate can be efficiently tuned. The observed non-local gating effect is initially driven by an in-plane electric field induced by the quantum capacitance of graphene, and further largely enhanced by adsorbed polarized water molecules. This study reveals a non-local phenomenon of Dirac electrons, provides a deep understanding of in-plane screening from Dirac electrons, and paves the way for designing novel electronic devices with remote gate control.
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http://dx.doi.org/10.1002/smll.202105687DOI Listing
November 2021

Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds.

J Mater Chem B 2021 12 8;9(47):9684-9699. Epub 2021 Dec 8.

National Engineering Research Center for Biomaterials, Chuanda-Jinbo Joint Research Center, Sichuan University, Chengdu 610064, People's Republic of China.

Recently, the incidence of chronic diabetic wounds increases continuously, and the existing clinical treatment is less effective. Thus, it is an urgent need to solve these problems for better clinical treatment effects. Herein, we prepared a brand-new tailored recombinant human collagen type III (rhCol III) and constructed a multifunctional microenvironment-responsive hydrogel carrier based on multifunctional antibacterial nanoparticles ([email protected] NPs) and our tailored rhCol III. The multifunctional smart hydrogel disintegrated quickly at the chronic diabetic wound sites and achieved the programed on-demand release of different therapeutic substances. The first released [email protected] NPs showed great antibacterial properties against and . They could kill bacteria rapidly, and also showed antioxidant and anti-inflammatory effects at the wound site. The subsequent release of our tailored rhCol III could promote the proliferation and migration of mouse fibroblasts and endothelial cells during the proliferation and remodeling process of wound healing. Relevant results showed that the multifunctional smart hydrogel could promote the expression levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), decrease the inflammatory response, accelerate the deposition of collagen and increase cell proliferation and angiogenesis, thereby speeding up the healing of infected chronic wounds. In a word, the hydrogel, which took into consideration the complex microenvironment at the wound site and multi-stage healing process, could achieve programmed and responsive release of different therapeutic substances to meet the treatment needs in different wound healing stages. More importantly, our work illustrated the great application potential of our brand-new rhCol III in promoting chronic wound repair and regeneration.
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http://dx.doi.org/10.1039/d1tb02170bDOI Listing
December 2021

Different performance of pyrene biodegradation on metal-modified montmorillonite: Role of surface metal ions from a bioelectrochemical perspective.

Sci Total Environ 2022 Jan 14;805:150324. Epub 2021 Sep 14.

Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Microbial extracellular electron transfer (EET) at microbe-mineral interface has been reported to play a significant role in pollutant biotransformation. Different metals often co-exist with organic pollutants and are immobilized on mineral surfaces. However, little is known about the influence of mineral surface metal ions on organic pollutant biodegradation and the involved electron transfer mechanism. To address this knowledge gap, pyrene was used as a model compound to investigate the biodegradation of polycyclic aromatic hydrocarbon on montmorillonite mineral saturated with metal ions (Na(I), Ni(II), Co(II), Cu(II) and Fe(III)) by Mycobacteria strain NJS-1. Further, the possible underlying electron transfer mechanism by electrochemical approaches was investigated. The results show that pyrene biodegradation on montmorillonite was markedly influenced by surface metal ions, with degradation efficiency following the order Fe(III) > Na(I) ≈ Co(II) > Ni(II) ≈ Cu(II). Bioelectrochemical analysis showed that electron transfer activities (i.e., electron donating capacity and electron transport system activity) varied in different metal-modified montmorillonites and were closely related to pyrene biodegradation. Fe(III) modification greatly stimulated degrading enzyme activities (i.e., peroxidase and dioxygenase) and electron transfer activities resulting in enhanced pyrene biodegradation, which highlights its potential as a technique for pollutant bioremediation. The bacterial extracellular protein and humic substances played important roles in EET processes. Membrane-bound cytochrome C protein and extracellular riboflavin were identified as the electron shuttles responsible for transmembrane and cross extracellular matrix electron transfer, respectively. Additions of exogenetic electron mediators of riboflavin, humic acid and potassium ferricyanide accelerated pyrene biodegradation which further verified the critical role of EET in PAH transformation at bacteria-mineral interfaces. These results support the development of clay mineral based advanced bioremediation techniques through regulating the electron transfer processes at the microbe-mineral interfaces by mineral surface modification.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150324DOI Listing
January 2022

A spatiotemporal release platform based on pH/ROS stimuli-responsive hydrogel in wound repairing.

J Control Release 2022 Jan 20;341:147-165. Epub 2021 Nov 20.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China.

Fabricating injectable hydrogel with multifunctions that matchs the highly ordered healing process of skin regeneration has greatly desired in treatment of chronic diabetic wounds. Herein, a pH/reactive oxygen species (ROS) dual responsive injectable glycopeptide hydrogel based on phenylboronic acid-grafted oxidized dextran and caffeic acid-grafted ε-polylysine was constructed, which exhibited inherent antibacterial and antioxidant capacities. The mangiferin (MF) with the ability to promote angiogenesis was encapsulated into pH-responsive micelles (MIC). Subsequently, diclofenac sodium (DS) with anti-inflammatory activities and [email protected] were embedded into the hydrogel. The hydrogel possessed good biodegradability, stable rheological property and self-healing ability, and could realize the spatiotemporal delivery of DS and MF. The in vitro and in vivo data showed that the hydrogel was biocompatible with effective anti-infection, anti-oxidation and anti-inflammation at early stages, then further promoted angiogenesis and accelerated wound repairing. Collectively, this novel glycopeptide hydrogel provides a facile and effective strategy for chronic diabetic wound repairing.
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http://dx.doi.org/10.1016/j.jconrel.2021.11.027DOI Listing
January 2022

Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Regulating Mitophagy via mTOR-ULK1/FUNDC1 Axis in Rats.

J Stroke Cerebrovasc Dis 2022 Jan 11;31(1):106202. Epub 2021 Nov 11.

Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

Objective: Electroacupuncture (EA) pretreatment has been shown to alleviate cerebral ischemia-reperfusion (I/R) injury; however, the underlying mechanism remains unclear. To investigate the involvement of mTOR signaling in the protective role of EA in I/R-induced brain damage and mitochondrial injury.

Methods: Sprague-Dawley male rats were pretreated with vehicle, EA (at Baihui and Shuigou acupoints), or rapamycin + EA for 30 min daily for 5 consecutive days, followed by the middle cerebral artery occlusion to induce I/R injury. The neurological functions of the rats were assessed using the Longa neurological deficit scores. The rats were sacrificed immediately after neurological function assessment. The brains were obtained for the measurements of cerebral infarct area. The mitochondrial structural alterations were observed under transmission electron microscopy. The mitochondrial membrane potential changes were detected by JC-1 staining. The alterations in autophagy-related protein expression were examined using Western blot analysis.

Results: Compared with untreated I/R rats, EA-pretreated rats exhibited significantly decreased neurological deficit scores and cerebral infarct volumes. EA pretreatment also reversed I/R-induced mitochondrial structural abnormalities and loss of mitochondrial membrane potential. Furthermore, EA pretreatment downregulated the protein expression of LC3-II, p-ULK1, and FUNDC1 while upregulating the protein expression of p-mTORC1 and LC3-I. Rapamycin effectively blocked the above-mentioned effects of EA.

Conclusion: EA pretreatment at Baihui and Shuigou alleviates cerebral I/R injury and mitochondrial impairment in rats through activating the mTORC1 signaling. The suppression of autophagy-related p-ULK1/FUNDC1 pathway is involved in the neuroprotective effects of EA.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106202DOI Listing
January 2022

Amelioration of Neuropathic Pain and Attenuation of Neuroinflammation Responses by Tetrahydropalmatine Through the p38MAPK/NF-κB/iNOS Signaling Pathways in Animal and Cellular Models.

Inflammation 2021 Nov 10. Epub 2021 Nov 10.

Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.

Neuropathic pain (NP) treatment remains a challenge because the pathomechanism is not yet fully understood. Because of low treatment efficacy, there is an important unmet need in neuropathic pain patients, and the development of a more effective pharmacotherapy is urgently required. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in NP. In this study, we aimed to investigate the protective properties of tetrahydropalmatine (THP) on a spared nerve injury (SNI) model of neuropathic pain in mice in in vivo and also in in vitro experiments. THP decreased mechanical hyperalgesia and cold allodynia compared with the SNI group. A microarray was applied to analyze differentially expressed of mRNA among different groups, and THP noticeably changed the expression of MAPK-related proteins compared with the SNI groups. H&E staining showed that the THP changed the inflammation after the spared nerve injury, with decreased NO expression in the THP group as compared to the SNI group. In addition, SNI-induced pain was reversed by intraperitoneal administration of THP, and further results indicated that THP suppressed inducible nitric oxide synthase (iNOS, pro-nociceptive mediators), phosphorylated MAPKs, and p65 in the dorsal root ganglions and sciatic nerve, while the serum levels of the pro-inflammatory cytokines IL-1β were significantly higher in the SNI group as compared to the THP group. To identify the molecular mechanism of the antineuropathic activity of THP, sodium nitroprusside (SNP)-induced neuro-2a (N2a) cells, LPS-induced BV2 cells, and LTA-induced astrocytes were further investigated in signaling pathways. In vitro experiments indicated that THP suppressed the expression of IL-1β, iNOS, phosphorylated MAPKs, and p65, which were assayed using western blotting, and immunofluorescence.
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http://dx.doi.org/10.1007/s10753-021-01593-xDOI Listing
November 2021

Intermittent Leucine Deprivation Produces Long-lasting Improvement in Insulin Sensitivity by Increasing Hepatic Gcn2 Expression.

Diabetes 2022 Feb;71(2):206-218

Chinese Academy of Sciences Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.

Leucine deprivation improves insulin sensitivity; however, whether and how this effect can be extended are unknown. We hypothesized that intermittent leucine deprivation (ILD) might produce a long-term effect on improved insulin sensitivity via the formation of metabolic memory. Consistently, seven ILD cycles of treatment (1-day leucine-deficient diet, 3-day control diet) in mice produced a long-lasting (after a control diet was resumed for 49 days) effect on improved whole-body and hepatic insulin sensitivity in mice, indicating the potential formation of metabolic memory. Furthermore, the effects of ILD depended on hepatic general control nondepressible 2 (GCN2) expression, as verified by gain- and loss-of-function experiments. Moreover, ILD increased Gcn2 expression by reducing its DNA methylation at two CpG promoter sites controlled by demethylase growth arrest and DNA damage inducible b. Finally, ILD also improved insulin sensitivity in insulin-resistant mice. Thus, ILD induces long-lasting improvements in insulin sensitivity by increasing hepatic Gcn2 expression via a reduction in its DNA methylation. These results provide novel insights into understanding of the link between leucine deprivation and insulin sensitivity, as well as potential nutritional intervention strategies for treating insulin resistance and related diseases. We also provide evidence for liver-specific metabolic memory after ILD and novel epigenetic mechanisms for Gcn2 regulation.
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http://dx.doi.org/10.2337/db21-0336DOI Listing
February 2022

Intrinsic Antibacterial and Conductive Hydrogels Based on the Distinct Bactericidal Effect of Polyaniline for Infected Chronic Wound Healing.

ACS Appl Mater Interfaces 2021 Oct 28. Epub 2021 Oct 28.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China.

Most chronic wounds suffer from infections, and their treatment is challenging. The usage of antibiotics may lead to bacterial resistance and adverse side effects. Positively charged substances have shown promise, but their applications are usually limited by certain cytotoxicity or complex synthesis. Doped polyaniline that carries a high density of positive charges would be a promising candidate due to its good biocompatibility and easy availability, but its interaction with bacteria has not been elucidated. Herein, the distinct bactericidal effect of polyaniline against Gram-positive bacteria has been verified. The antibacterial activity may result from the specific interaction with lipoteichoic acid to destroy the Gram-positive bacterial cell wall. Polyaniline and a macromolecular dopant (sulfonated hyaluronic acid) are used to construct a flexible hydrogel with skin-mimic electrical conductivity. The in vivo results demonstrate that electrical stimulation (ES) through this hydrogel is superior to ES via separated electrodes (the ES strategy used clinically) for promoting infected chronic wound healing.
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http://dx.doi.org/10.1021/acsami.1c14088DOI Listing
October 2021

Hepatic P38 Activation Modulates Systemic Metabolism Through Fgf21-Mediated Interorgan Communication.

Diabetes 2021 Oct 21. Epub 2021 Oct 21.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of 1CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Sciences; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China;

The mechanisms underlying the pathogenesis of steatosis and insulin resistance in nonalcoholic fatty liver disease remain elusive. Increased phosphorylation of hepatic p38 has long been noticed in fatty liver; however, whether the activation of hepatic p38 is a cause or consequence of liver steatosis is unclear. Here, we demonstrate that hepatic p38 activation by MKK6 overexpression in the liver of mice induces severe liver steatosis, reduces fat mass, and elevates circulating fatty acid levels in a hepatic p38α- and FGF21-dependent manner. Mechanistically, through increasing the FGF21 production from liver, hepatic p38 activation increases the influx of fatty acids from adipose tissue to liver, leading to hepatic ectopic lipid accumulation and insulin resistance. Although hepatic p38 activation exhibits favorable effects in peripheral tissues, it impairs the hepatic FGF21 action by facilitating the ubiquitination and degradation of FGF21 receptor cofactor β-Klotho. Consistently, we show that p38 phosphorylation and FGF21 expffression are increased, β-Klotho protein levels are decreased in the fatty liver of either mice or patients. In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38α, FGF21, and β-Klotho in the pathogenesis of nonalcoholic fatty liver disease.
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http://dx.doi.org/10.2337/db21-0240DOI Listing
October 2021

The Effectiveness of Traditional Chinese Medicine Jinlida Granules on Glycemic Variability in Newly Diagnosed Type 2 Diabetes: A Double-Blinded, Randomized Trial.

J Diabetes Res 2021 8;2021:6303063. Epub 2021 Oct 8.

Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

This study aimed to evaluate the influence of Jinlida granules on glycemic variability with or without metformin treatment in patients with newly diagnosed type 2 diabetes. This study was a 16-week, double-blinded, randomized, controlled clinical trial. The enrolled patients with newly diagnosed type 2 diabetes were randomly divided into four groups: control, Jinlida, metformin, and combination treatment groups. A retrospective continuous glucose monitoring (CGM) system was used for subcutaneous interstitial glucose monitoring for 3 days consecutively. Hemoglobin A1c (HbA1c), traditional Chinese medicine symptom score, and CGM parameters, including glucose coefficient of variation, standard deviation of blood glucose values, and time in range of glucose 3.9-10.0 mmol/L, were assessed pre-test and post-test. A total of 138 participants completed the entire procedure. Compared with the pre-test, fasting plasma glucose, 2 hour postprandial plasma glucose, HbA1c, and traditional Chinese medicine symptom score all decreased in the four groups at the end of the test, and the combination treatment group showed the most significant decrease. In terms of CGM parameters, time in range of the Jinlida and metformin groups improved after intervention compared with the baseline (Jinlida group: 78.68 ± 26.15 versus 55.47 ± 33.29; metformin group: 87.29 ± 12.21 vs. 75.44 ± 25.42; P < 0.01). Additionally, only the Jinlida group showed decreased glucose standard deviation after intervention (1.57 ± 0.61 vs. 1.96 ± 0.95; P < 0.01). Jinlida granules can improve glycemic control and glycemic variability in patients with newly diagnosed type 2 diabetes. : ChiCTR-IOR-16009296.
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http://dx.doi.org/10.1155/2021/6303063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519714PMC
October 2021
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