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Abstract Background: The α/β-hydrolase domain 2 (ABHD2) genes which was expressed in the alveolar type II cells (AT-II cells) have been identified as down-regulated genes in human emphysematous lungs. Meanwhile, ABHD2 is considered a triacylglycerol lipase. We investigated how the ABHD2 gene is involved in the development of emphysema by affecting lipid metabolism. Methods: We treated A549 cells (whose biological characteristics were similar to those of AT-II cells) with/without ABHD2 knockdown at 0,50,100umol/L palmitic acid (PA). The cells were stained by Oil Red O, probe DCFH-DA, Annexin V-FITC/PI. The contents of intracellular triglyceride, MDA, Caspase-3 activity and cell viability were determined. We analyzed of C57BL6 and Abhd2 knockdown mice at different ages. The triglyceride, cholesterol and MDA level in mouse serum were measured. The contents of triglyceride, Malondialdehyde (MDA), Caspase-3 activity in mouse lung tissues were determined. The lung tissues were stained with hematoxylin and eosin, Oil Red O and TUNEL. Results: We found that there were excessive deposition of triglyceride, lipid peroxidation, decreased cell viability and increased apoptosis in the cells with ABHD2 knockdown, showing lipid toxicity. At the same time, ABHD2 knockdown aggravates the lipid toxicity induced by PA in the A549 cells. ABHD2 deficiency resulted in abnormal lipid metabolism and lipid peroxidation in serum of mice. Meanwhile, these mice developed spontaneous gradual progression of emphysema, due to abnormal lipid metabolism, lipid peroxidation and enhanced apoptosis in lung tissues of ABHD2 knockdown mice. Conclusions: Our findings suggest that ABHD2 knockdown can induce emphysema by accelerating triglyceride deposition. Keywords: ABHD2 knockdown, Emphysema, ATGL, Triglyceride Deposition, lipid toxicity

Mei-Yu Lv, Li-Xia Qiang, Bao-Cai Wang, Yue-Peng Zhang, Zhi-Heng Li, Xiang-Shun Li, Ling-Ling Jin, Shou-De Jin Department of Respiratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Shou-De Jin, Department of Respiratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, No. 37 Yiyuan Street, Nangang District, Harbin, 150001, People’s Republic of China, Tel/Fax +86 0451-85939123, Email jinshoude@163.comPurpose: Pulmonary surfactant proteins A (SP-A) and D (SP-D) are lectins, involved in host defense and regulation of pulmonary inflammatory response. However, studies on the assessment of COPD progress are limited.Patients and Methods: Pulmonary surfactant proteins were obtained from the COPD mouse model induced by cigarette and lipopolysaccharide, and the specimens of peripheral blood and bronchoalveolar lavage (BALF) in COPD populations. H&E staining and RT-PCR were performed to demonstrate the successfully established of the mouse model. The expression of SP-A and SP-D in mice was detected by Western Blot and immunohistochemistry, while the proteins in human samples were measured by ELISA. Pulmonary function test, inflammatory factors (CRP, WBC, NLR, PCT, EOS, PLT), dyspnea index score (mMRC and CAT), length of hospital stay, incidence of complications and ventilator use were collected to assess airway remodeling and progression of COPD.Results: COPD model mice with emphysema and airway wall thickening were more prone to have decreased SP-A, SP-D and increased TNF-α, TGF-β, and NF-kb in lung tissue. In humans, SP-A and SP-D decreased in BALF, but increased in serum. The serum SP-A and SP-D were negatively correlated with FVC, FEV1, FEV1/FVC, and positively correlated with CRP, WBC, NLR, mMRC and CAT scores (P < 0.05, respectively). The lower the SP-A and SP-D in BALF, the worse the lung function and the increased probability of complications and ventilator use. Moreover, the same trend emerged in COPD patients grouped according to GOLD severity grade (Gold 1– 2 group vs Gold 3– 4 group). The worse the patient’s condition, the more pronounced the change.Conclusion: This study suggests that SP-A and SP-D may be related to the progression and prognostic evaluation of COPD in terms of airway remodeling, inflammatory response and clinical symptoms, and emphasizes the necessity of future studies of surfactant protein markers in COPD.Keywords: COPD, pulmonary surfactant protein A and D, airway remodeling

Fast electron beams (FEBs) are one of the main products of various active events and are ubiquitous in solar, space and cosmic plasmas. They reveal themselves in hard X-ray and radio emissions. The observed characteristics of X-ray and radio emissions sensitively depend on the energy distribution of FEBs, which usually have a power-law energy spectrum. As FEBs travel in the solar atmosphere, their energy distribution can considerably vary due to the interaction with ambient plasmas. Tang et al. investigated the evolution of the energy spectrum of the FEBs traveling along a flare loop and discussed the possible effects on associated hard X-ray (HXR) and radio emissions. Considering the ubiquitous coronal loops in active regions, in the present paper, we investigate the parametric evolution of the energy spectra of FEBs when propagating along coronal loops. Here, we take the sunpot atmospheric model as an approximate coronal loop atmosphere model. The results show that the energy loss has an important impact on the cutoff behavior and energy spectra of FEBs when precipitating in a coronal loop with density ratio n b /n e = 0.01. The initially single power-law spectrum with a steepness cutoff can evolve into a more complex double power-law spectrum or two “knees” power-law spectrum with a flattened steepness cutoff behavior or saturation cutoff behavior. Our calculations also demonstrate that the energy spectrum evolution is not obvious if n b /n 0 = 0.001 as Tang et al. asserted. The present results are helpful for a more comprehensive understanding of the dynamic spectra of HXR and radio emissions from FEBs.

The cerebral ischemia-reperfusion (I/R) model is crucial for the study of cerebral stroke. Chrysophanol (Chry) can protect nerve damage of mice in cerebral ischemia-reperfusion injury. This study aimed at investigating the neuroprotective effects of chrysophanol through mitochondrial autophagy in mice with ischemia-reperfusion injury.Adult mice were stochastically divided into five groups: sham, I/R (solvent), I/R+Chry (dose, 10.0ml/kg), I/R+Chry (dose, 1.0ml/kg), and I/R+Chry (dose, 0.1ml/kg). The cerebral ischemia-reperfusion model was made in I/R and I/R+Chry groups. The changes in hippocampal formation were observed by hematoxylin and eosin (HE) staining. The expressions of LC3B-II and LC3B-I protein in hippocampus were demonstrated by western blot (WB). The fluorescence intensities of NIX, LC3B, and mitochondria were detected by immunohistochemistry fluorescent (IF).Comparing with the I/R group, the I/R+Chry groups showed improvements in reducing the damage on the hippocampus, indicated by the reduced ratio of LC3B-II and LC3B-I protein, decreased fluorescence intensity of NIX and LC3B, and increased intensity of mitochondrial fluorescence.Our study showed that chrysophanol may regulate mitochondrial autophagy through NIX protein and alleviate the damage of hippocampus through decreasing the level of mitochondrial autophagy.

ObjectiveThis study aimed at examining the long-term effects of non-pharmacological interventions on reducing the diabetes incidence among patients with prediabetes and chronic complications events among patients with hyperglycemia (pre-diabetes and diabetes) by performing a systematic review and meta-analysis of randomized controlled trials (RCTs).MethodsPubMed, MEDLINE, EMBASE, the Cochrane Library, and the Web of Science Core Collection were searched for studies published between January 1990 and November 2021, looking for RCTs to evaluate the effects of non-pharmacological interventions on preventing the incidence of diabetes and chronic complications in comparison with medical therapy, placebo, or usual diabetes care. Two independent reviews extracted relevant data and quality assessment. Any discrepancies were resolved by a third reviewer.ResultsIn total, 20 articles involved 16 RCTs (follow-up ranged from 2 to 30 years) were included. Pooled analysis of intervention studies demonstrated clearly that non-pharmacological interventions have a significant effect on reducing the diabetes events in patients with prediabetes (RR 0.62; 95% CI 0.54, 0.71). Pooled analysis of extended follow-up studies showed that non-pharmacological interventions could effectively reduce the diabetes incidence in patients with prediabetes (RR 0.78; 95% CI 0.63, 0.96). Meta-regression and subgroup analysis indicates that the diabetes incidence of the long-term group (duration > 3 years) was clearly reduced by 0.05% compared with the relatively short-term group (duration ≤ 3 years). The incidence of microvascular complications in patients with hyperglycemia was effectively lowered by non-pharmacological interventions (RR 0.60; 95% CI 0.43, 0.83).ConclusionNon-pharmacological interventions have a long-term effect on reducing the diabetes incidence among prediabetic patients and effectively preventing microvascular complications on hyperglycemia.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/.

Diabetic kidney disease (DKD), one of the most important diabetic complications, is a great clinical challenge. It still lacks proper therapeutic strategies without side effects due to the complex pathological mechanisms.

Objective. To explore the main bioactive compounds and investigate the underlying mechanism of Pollen Typhae (PT) against diabetic retinopathy (DR) by network pharmacology and molecular docking analysis. Methods. Bioactive ingredients and the target proteins of PT were obtained from TCMSP, and the related target genes were acquired from the SwissTargetPrediction database. The target genes of DR were obtained from GeneCards, TTD database, DisGeNET database, and DrugBank. The compound-target interaction network was established based on Cytoscape 3.7.2. The protein-protein interaction (PPI) network was constructed via STRING database and Cytoscape 3.7.2. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were visualized through DAVID database and Bioinformatics. Ingredient-gene-pathway network analysis was conducted to further screen the ingredients, target proteins, and pathways closely related to the biological mechanism on PT for DR, and molecular docking analysis was performed by SYBYL-X 2.1.1 software. Finally, the mechanism and underlying targets of PT in the treatment of DR were predicted. Results. A total of 8 compounds and 171 intersection targets were obtained based on the online network database. 7 main compounds were screened from compound-target network, and 53 targets including the top six key targets (PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR) were further acquired from PPI analysis. The 53 key targets covered 80 signaling pathways, among which PI3K-Akt signaling pathway, focal adhesion, Rap1 signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway were closely connected with the biological mechanism involved in the alleviation of DR by PT. Ingredient-gene-pathway network shows that AKTI, EGFR, and VEGFA were core genes, kaempferol and isorhamnetin were pivotal ingredients, and VEGF signaling pathway and Rap1 signaling pathway were closely involved in anti-DR. The docking results indicated that five main compounds (arachidonic acid, isorhamnetin, quercetin, kaempferol, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) had good binding activity with EGFR and AKT1 targets. Conclusion. The active ingredients in PT may regulate the levels of inflammatory factors, suppress the oxidative stress, and inhibit the proliferation, migration, and invasion of retinal pericytes by acting on PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR targets through VEGF signaling pathway, PI3K-Akt signaling pathway, Rap1 signaling pathway, and HIF-1 signaling pathway to play a therapeutic role in diabetic retinopathy.

Diabetic kidney disease (DKD), one of the most important diabetic complications, is a great clinical challenge. It still lacks proper therapeutic strategies without side effects due to the complex pathological mechanisms. Cornus officinalis (CO) is a common traditional Chinese medicine, which has been used in the treatment of DKD and takes beneficial effects in therapy. However, the mechanism of CO in treating DKD is not clear yet. In this study, network pharmacology was applied to illustrate the potential mechanism of CO and the interaction between targets of CO and targets of disease. First, the active ingredients of CO and related targets were screened from the online database. Second, the intersection network between CO and disease was constructed, and protein–protein interaction analysis was done. Third, GO and KEGG analysis were employed to figure out the key targets of CO. Finally, molecular docking was carried out in the software SYBYL to verify the effectiveness of the ingredients and targets selected. According to GO and KEGG analysis, drug metabolism-cytochrome P450, sphingolipid signaling pathway, HIF-1 signaling pathway, TGF-beta signaling pathway, cGMP-PKG signaling pathway, estrogen signaling pathway, and TNF signaling pathway were most closely related to the pathogenesis of DKD. Moreover, NOS3, TNF, ROCK1, PPARG, KDR, and HIF1A were identified as key targets in regulating the occurrence and development of the disease. This study provides evidence to elucidate the mechanism of CO comprehensively and systematically and lays the foundation for further research on CO.

The complex [Dy4(L1)2(CH3COO)4(DMF)3] (1) was obtained by using 2,6-bis(2-((E)-(8-hydroxyquinolin-2-yl)methylene)hydrazine-1-carbonyl)pyridine 1-oxide (H4L1) and Dy(CH3COO)3·4H2O under 100 in N,N-dimethylformamide (DMF) solvent. Structure analyzing showed that Dy(III) ions had two types of configuration with D2d and C4v. AC magnetic susceptibilities exhibited that complex 1 was an obvious single-molecule magnet (SMM) with obvious ac susceptibilities at zero Oe static magnetic field over the frequency range of 9–999 Hz. These findings demonstrated potential applications of polydentate ligands for the synthesis of SMMs.

We successfully obtained two type of heterometallic complexes [Fe4Dy2(L1)2(µ4-O)2(piv)4(H2O)2(NO3)4]·CH3CN·CH3OH (1) and [Fe6Dy2(L1)2(µ4-O)2(CH3COO)6(OH)2(H2O)2(NO3)6]·CH3CN (2) by using 2,2′-((2-((2-hydroxyethyl)amino)cyclohexyl)azanediyl)bis(ethan-1-ol) (H3L1), Dy(NO3)3·6H2O, FeCl3 and pivalic acid (piv) or acetic acid under room temperature in different solvent. Crystal structure showed that the central structure of [ $${{\text{Fe}}}_{4}^{{\text{III}}}$$ (µ4-O)2]8+ arranged in what was often termed an absent cubic shape, although here the Fe centers were strictly coplanar. Each Fe3 triangle was connected to the capping Dy(III) through µ4-O bridges for complex 1, and each Fe3 triangle was connected to the capping Fe(III) through µ4-O bridges for complex 2. It might be due to the steric effect that the coordination atoms of piv ligands chelated and blocked the structure. AC magnetic susceptibilities exhibited that complex 1 and 2 showed out-of-phase (χ″) component of ac-susceptibilities at zero Oe static magnetic field over the frequency range of 9–999 Hz, which energy barriers were 0.44 and 0.13 K. And their energy barriers were 1.2 and 12.2 K at applied 1000 Oe static magnetic field.

Introduction Radix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach. Methods A network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, “degree” and “closeness certainty” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. Results A total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy. Conclusions Radix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.

Background The previous study found that the Jinlida could significantly reduce levels of blood glucose and enhance the lowing-glucose action of metformin. However, the role of the standard-reaching rate of blood glucose and improving clinical symptoms in Jinlida has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in Type 2 diabetics who experience clinical symptoms based on secondary analysis from the 12-week trial. Methods Data were analyzed from a 12-week, randomized, placebo-controlled, study of Jinlida. The standard-reaching rate of blood glucose, total symptom score, the efficacy of single symptom, symptom disappearance rate, symptom improvement rate was evaluated. Then, the correlation of the symptom effective rate and HbA1c was analyzed. Results 192 T2DM patients were randomly allocated to receive either Jinlida or a placebo for 12 consecutive weeks. The standard-reaching rate of HbA1c (

Background: Type 2 diabetes mellitus (T2DM) complicated with dyslipidaemia is associated with a high risk of cardiovascular diseases. The Jiangtang Tiaozhi (JTTZ) recipe is a Chinese herbal formula that has been used to regulate the blood glucose and lipid levels for many years. Interestingly, a previous study has demonstrated its efficacy; however, the associated mechanism remains unclear. We hypothesised that the therapeutic effect of the JTTZ on patients with T2DM may be mediated by the modulation of metabolites secreted by the gut microbiota. This study aims to examine this mechanism.Methods and analysis: This study is a randomised, positive drug parallel-controlled, open-label clinical trial in patients with T2DM and dyslipidaemia. A total of 96 patients will be recruited and randomly assigned to treatment with JTTZ or metformin for 12 weeks. The primary outcome will be the rates of effectively regulated blood glucose and lipid levels (measured with the levels of glycated haemoglobin, fasting plasma glucose, 2-h plasma glucose, triglyceride, and low-density lipoprotein cholesterol). The secondary outcomes will be the changes in body weight, body mass index, and waist circumference and Traditional Chinese Medicine symptom scores. In addition, 16S rRNA gene sequencing will be performed on the gut microbiota obtained from faeces, and metabolomics analysis will be performed based on blood and gut microbiota samples. Intention-to-treat, per-protocol analysis and safety analysis will be performed.Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT04623567

The anticoagulant application is an effective treatment modality for cardiovascular diseases such as coronary heart disease, unstable angina pectoris, and myocardial infarction. In this study, the antithrombotic effect of recombinant neorudin (EPR-hirudin, EH) was evaluated using a canine model of coronary artery thrombosis. A canine model with platelet thrombosis in the left circumferent branch of the coronary artery was designed using Folt's method, and the anti-thrombus activity of EH was investigated. Femoral administration of EH intravenously had a significant dose-dependent inhibitory effect on canine coronary artery thrombosis and the effective rates were 66.7% (p .05), 83.3% (p .05), and 100% (p .01) after injection of 0.3, 1.0, and 3.0 mg/kg EH, respectively. Furthermore, EH demonstrated lower bleeding, with shorter bleeding time and less bleeding loss than low molecular weight heparin (LMWH). Under the similar effect intensity of EH and LMWH (85 IU/kg), the bleeding time of the EH group at 30 min was shorter, and the blood loss at 30-120 min was less than that of LMWH (p .05 and p .05-.001, respectively). EH had a significant dose-dependent inhibitory effect in the dose range of 0.3-3.0 mg/kg on the coronary artery thrombosis and lower bleeding side effects than LMWH with a similar antithrombosis effect.

Diabetic kidney disease (DKD), as the most common complication of diabetes mellitus (DM), is the major cause of end-stage renal disease (ESRD). Renal interstitial fibrosis is a crucial metabolic change in the late stage of DKD, which is always considered to be complex and irreversible. In this review, we discuss the pathological mechanisms of diabetic renal fibrosis and discussed some signaling pathways that are closely related to it, such as the TGF-β, MAPK, Wnt/β-catenin, PI3K/Akt, JAK/STAT, and Notch pathways. The cross-talks among these pathways were then discussed to elucidate the complicated cascade behind the tubulointerstitial fibrosis. Finally, we summarized the new drugs with potential therapeutic effects on renal fibrosis and listed related clinical trials. The purpose of this review is to elucidate the mechanisms and related pathways of renal fibrosis in DKD and to provide novel therapeutic intervention insights for clinical research to delay the progression of renal fibrosis.

Traditional Chinese medicine (TCM) prescriptions lack standardization due to the complex composition of the prescribed herbs, the unclear mechanism of the formulas, and a lack of scientific data to support the dose-response relationship. Here, we proposed a new clinical strategy of dosage modification for TCM prescriptions to evaluate the clinical efficacy and guide the clinical medication. This study used two TCM prescriptions for the treatment of newly diagnosed type 2 diabetes mellitus (T2DM) to explore the key indications and the most appropriate critical values of dosage modification by analyzing two randomized controlled trials (RCTs). In this study, the indications refer to a change in the indicators from baseline at a certain time point (week 4, week 8, week 12), which could predict the change in outcome indicators, and the critical values refer to the change ranges closely related to the decrease in HbA1c at week 12. In Study 1, the correlation analysis between the change range of indicators at three time points (weeks 4, 8, and 12) from baseline and the decrease in HbA1c at week 12 from baseline (HbA1c 012) was carried out to screen the related indications. Next, we evaluate the related indications and the respective critical values to determine the key indicators, indications, and the most appropriate critical value. We conducted a correlation between the change range of key indicators (obtained from the result of Study 1) at three time points from baseline and HbA1c 012 to screen the key indications in the drug group, high-dose group, and low-dose group in Study 2. Key indications with critical values were determined to investigate the most appropriate critical value in the three groups separately. In Study 1, the key indicator was FBG, the key indication was FBG 04, and the most appropriate critical value was 0.5 mmol/L. In Study 2, the key indication was FBG 04 and the most appropriate critical value was 0.6 mmol/L in the drug group. In the high-dose group, the key indication was FBG 04, and the most appropriate critical value was 0.3 mmol/L. In the low-dose group, the key indication was FBG08, and the most appropriate critical value was 0.1 mmol/L. In addition, we summarized a verification strategy for dosage modification.

BackgroundA detailed means of prognostic stratification in patients with non-small cell lung cancer (NSCLC) is urgently needed to support individualized treatment plans. Recently, microRNAs (miRNAs) have been used as biomarkers due to their previously reported prognostic roles in cancer. This study aimed to construct an immune-related miRNA signature that effectively predicts NSCLC patient prognosis.MethodsThe miRNAs and mRNA expression and mutation data of NSCLC was obtained from The Cancer Genome Atlas (TCGA). Immune-associated miRNAs were identified using immune scores calculated by the ESTIMATE algorithm. LASSO-penalized multivariate survival models were using for development of a tumor immune-related miRNA signature (TIM-Sig), which was evaluated in several public cohorts from the Gene Expression Omnibus (GEO) and the CellMiner database. The miRTarBase was used for constructing the miRNA-target interactions.ResultsThe TIM-Sig, including 10 immune-related miRNAs, was constructed and successfully predicted overall survival (OS) in the validation cohorts. TIM-Sig score negatively correlated with CD8+ T cell infiltration, IFN-γ expression, CYT activity, and tumor mutation burden. The correlation between TIM-Sig score and genomic mutation and cancer chemotherapeutics was also evaluated. A miRNA-target network of 10 miRNAs in TIM-Sig was constructed. Further analysis revealed that these target genes showed prognostic value in both lung squamous cell carcinoma and adenocarcinoma.ConclusionsWe concluded that the immune-related miRNAs demonstrated a potential value in clinical prognosis.

Treatment of late-stage lung cancer has witnessed limited advances. In contrast to the tremendous efforts toward improving adaptive immunity, approaches to modulating innate immunity are relatively immature. As important innate immune cells, tumor-associated macrophages (TAMs) account for a substantial fraction of tumor-infiltrating lymphocytes, which not only reverses the immune-suppressive tumor microenvironment but also facilitates an adaptive immune response. In this study, we developed a tumor-specific MMP-2-responsive CD47 blockage (TMCB) strategy to enable effective cancer immunotherapy. Briefly, the matrix metalloproteinase-2 (MMP-2)-responsive self-assembly peptide specifically recognizes CD47, which is highly expressed in lung tumor cells. Second, the MMP-2-responsive self-assembly peptide is efficiently cleaved by MMP-2, which is overexpressed in the tumor microenvironment. Finally, the generated residual peptide naturally self-assembles into peptide-based nanofibers. The in situ constructed nanofibers inhibit the canonical CD47 "Do not eat me" signal expressed on tumor cells to promote phagocytosis of tumor cells by macrophages, which further induces effective antigen presentation and initiates T cell-mediated adaptive immune responses to inhibit tumor growth. Thus, we described a peptide-based TMCB strategy that induces both innate and adaptive immune systems to inhibit tumor growth.

Background: T2DM is considered to be a chronic low-grade inflammatory disease, because of its high morbidity and mortality, diabetes poses a tremendous potential threat to public health. Our previous studies have shown that a traditional Chinese medicine formula, Jiedu Tongluo Tiaogan Formula (JDTL) exerts favorable hypoglycemic effect, however, its molecular mechanism and the interaction among various components need to be further elucidated. This study aimed to explore the mechanism of JDTL in the treatment of T2DM using an integrated strategy of system pharmacology, bioinformatics analysis, and experimental verification. Materials and Methods: First, the compounds of JDTL were searched from public databases, and the "compound-target " network was constructed to predict the potential active components and targets. Subsequently, bioinformatics analysis was used to identify potential targets and signaling pathways, including PPI, GO pathways and KEGG pathways. Finally, the pharmacological effects and mechanisms of JDTL were verified by molecular docking and cell experiments. Results: Analysis by GO and KEGG pathway enrichment revealed that these targets were associated with lipopolysaccharide, membrane microdomain, cytokine receptor binding, and JDTL could regulate the PI3K/Akt signaling pathway. Furthermore, we have proved that JDTL could improve the mRNA expression and protein expression of IRS1, AKT, and PI3K in the INS-1 cell and HepG2 cells. Conclusion: The present study elucidated the active ingredients, potential targets, and molecular mechanism of JDTL in the treatment of T2DM, and revealed the characteristics of JDTL in multi-component, multi-target and multi-channel. It also provided an important scientific basis for new drug development and mechanism research of T2DM.

Panax ginseng C.A.Mey. has been widely consumed as food/diet supplements from natural sources, and its therapeutic properties have also aroused widespread concern. Therapeutic properties of Panax ginseng C.A.Mey. such as anti-inflammatory, ameliorating chronic inflammation, enhancing the immunity, resisting the oxidation again, and regulating the glucose and lipid metabolism have been widely reported. Recent years, lots of interesting studies have reported the potential use of Panax ginseng C.A.Mey. in the management of DKD. DKD has become the leading cause of end-stage renal disease worldwide, which increases the risk of premature death and poses a serious financial burden. Although DKD is somehow controllable with different drugs such as Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB) and lowering-glucose agents, modern dietary changes associated with DKD have facilitated research to assess the preventive and therapeutic merits of diet supplements from natural sources as medicine including Panax ginseng C.A.Mey. Findings from many scientific evidences have suggested that Panax ginseng C.A.Mey. can relieve the pathological status in cellular and animal models of DKD. Moreover, a few studies showed that alleviation of clinical phenotype such as reducing albuminuria, serum creatinine and renal anemia in DKD patients after application or consumption of Panax ginseng C.A.Mey.. Therefore, this review aims to discuss the effectiveness of Panax ginseng C.A.Mey. as medicine for targeting pathological phenotypes in DKD from a pharmacological perspective. This review will provide new insights into the potential understanding use of Panax ginseng C.A.Mey. in the management of DKD in clinical settings.

This paper presents the analysis to reduce carbon emission from tugboat operations by utilizing a proposed unsupervised machine learning operational scoring system. The time-series analysis is performed by transforming data into a common domain for clustering. The data are collected from a tugboat to investigate the correlation between environmental and location data with fuel consumption to achieve fuel efficiency. The relevant parameters that influence the fuel consumption of the tugboat, such as fuel consumption, vessel route, vessel speed and wind metrics are collected from sensors installed onboard the ship and data provider to monitor and to gauge the vessel’s performance. The raw readings are conditioned (data cleaning and data pre-processing) before transformation to Score Dataset: the Raw mass-flowrate readings are cleaned by using the Haar wavelet; the wind raw reading is converted to wind effect data; the Location data is converted to vessel speed data. Together, they form a Score Dataset by applying the time series K-means clustering. The subsequent unsupervised learning identifies the activity labels that describe qualitatively the operations of the vessels and are obtained by using the non-time series K-mean clustering. By using the Hidden Markov Model approach, this paper attempts to explain the stochastic correlation among parameters explained earlier. The correlation is the information of newly discovered knowledge in terms of likelihood matrices, also known as the knowledge base (KB). The KB may be consumed to perform predictions. Hence, it is possible to suggest the optimal ship operation, i.e., speed that produces the optimum fuel consumption. The Score Dataset and clustering that are produced in this paper could also be used in the Artificial Neural Network for future work.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first broke out in Wuhan, China, in 2019. SARS-CoV-2 develops many types of mutations (such as B.1.1.7), making diagnosis and treatment challenging. Although we now have a preliminary understanding of COVID-19, including pathological changes, clinical manifestations, and treatment measures, we also face new difficulties. The biggest problem is that most COVID-19 patients might face sequelae (e.g., fatigue, sleep disturbance, pulmonary fibrosis) during the recovery phase. We aimed to test six Chinese patent medicines to treat three major abnormal symptoms in COVID-19 patients during the recovery phase, including cardiopulmonary function, sleep disturbance, and digestive function. We launched the “three syndromes and six Chinese patent medicines” randomized, double-blind, placebo-controlled, multicenter clinical trial on April 10, 2020. The results showed that Jinshuibao tablets and Shengmaiyin oral liquid significantly improved the cardiopulmonary function of recovering COVID-19 patients. Shumian capsules, but not Xiaoyao capsules, significantly improved patients’ sleep disorders. This might be because the indication of Xiaoyao capsules is liver qi stagnation rather than psychological or emotional problems. Xiangsha Liujun pills and Ludangshen oral liquid significantly improved digestive function. Our research provides a guideline for treating COVID-19 sequelae in patients during the recovery period based on high-quality evidence.

Background: Previous studies have showed that traditional Chinese medicine can regulate glycaemia, bodyweight, lipids, and blood pressure in populations with various different cardiovascular risk factors. Yet no studies have established the benefits of traditional Chinese medicine in patients with type 2 diabetes with dyslipidaemia and abdominal obesity. We aimed to assess the efficacy and safety of the Jiangtangtiaozhi decoction (known as JTTZF), a Chinese herbal medicine, on glycaemia, lipids, and weight variables, compared with metformin. Methods: We did a randomised, multicenter, clinical trial in nine research centres in China. Adult patients (aged 18-70 years old) with type 2 diabetes and dyslipidaemia (defined as triglyceride 1.70-5.65 mmol/L-1) inadequately controlled by diet and exercise were enrolled. Patients were randomly allocated (1:1) via a computer-generated randomisation sequence to receive JTTZF (30g, twice per day) or metformin (0.25 g, three times a day) for 48 consecutive weeks. Patients were treated with gliclazide sustained-release tablets once per day when their HbA1c was more than 7% after 24 weeks. If their triglyceride was more than 5.65 mmol/L-1, bezafibrate was given twice a day. Patients and clinicians were masked to group assignment. The primary endpoint was change from baseline to week 48 of mean HbA1c in each treatment group. Secondary endpoints included lipid concentrations (ie, triglyceride, total cholesterol, LDL, and HDL), waist circumference, bodyweight, and BMI. Analyses were done in the per-protocol population who complied with the protocol and had no violations. Percentages of patients that reached HbA1c targets (Results: Between Nov 25, 2011, and Jun 27, 2013, we randomly assigned 450 patients to either JTTZF (n=225) or to metformin (n=225). 378 patients were included in the per-protocol analysis (201 patients in the JTTZF group and 177 patients in the metformin group). At week 48, JTTZF reduced mean HbA1c to 7.30% (SD 1.21, -0.94% from baseline) and metformin reduced mean HbA1c to 7.23% (SD 1.15, -1.00% from baseline; p=0.55 for difference between groups). 46% of patients attained the HbA1c goal in the JTTZF group and 41% in the metformin group. Compared with metformin, JTTZF did not significantly reduce mean concentrations of triglycerides (-0.87 mmol/L, SD 2.73 in the JTTZF group vs -0.53 mmol/L, 2.33 in the metformin group; p=0.19), total cholesterol (-0.53 mmol/L, 1.36 vs -0.39 mmol/L, 1.27; p=0.324), LDL (-0.45 mmol/L, 1.00 vs -0.33 mmol/L, 0.82; p=0.204), and HDL (-0.08 mmol/L, 0.43 vs -0.06 mmol/L, 0.27; p=0.54). More patients in the JTTZF than the metformin group reached targets for triglycerides (42% vs 28%, p=0.007) and total cholesterol (78% vs 69%, p=0.047). After 48 weeks, compared with metformin, JTTZF decreased mean waist circumference (-4.15 cm, SD 5.41 vs -2.95 cm, 5.70; p=0.036), bodyweight (-2.72 kg, SD 4.29 vs -1.75 kg, 4.31; p=0.029), and BMI (-0.99 kg/m², SD 1.55 vs -0.62 kg/m², SD 1.59; p=0.021). Serious adverse events were reported in four (2%) of 225 patients in the JTTZF group and in six (3%) of 225 patients in the metformin group. No severe hypoglycaemia was reported in either group.Conclusions: JTTZF showed improvements in several cardiovascular risk factors compared with metformin. JTTZF might be a promising alternative treatment for patients with type 2 diabetes.Trial registration Clinicaltrials.gov Identifier: NCT01471275

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%, HR, 2.93, 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

Background Determining the optimal management of right anomalous coronary artery from the opposite sinus (R-ACAOS) with an interarterial course (IAC) in middle-aged adults remains elusive. Hybrid cardiac imaging combining non-invasive and invasive approaches to identify high-risk anatomic features, as well as functional testing to assess potential ischaemic status by dynamic compression, can guide therapeutic decisions. Case summary A 65-year-old female was newly diagnosed with R-ACAOS with IAC, accompanied by suspected angina and two syncope episodes. She was initially considered as non-specific chest pain based on negative treadmill test (TMT) taken 10 years earlier. An anomaly of R-ACAOS with IAC travelling between the aorta and pulmonary artery was detected by coronary computed tomography angiography with a severe stenosis at the ostium, but with little evidence of atherosclerotic plaque. Exercise test (TMT) and single-photon emission computed tomography (SPECT) results were negative. Invasive imaging revealed a luminal area stenosis of 45% at the ostial right coronary artery, and a slit-like orifice anatomical feature, with a minimal lumen area of 5.81 mm2 at diastole determined by intravascular ultrasound. Based on hybrid cardiac imaging results and previous data from a case series, conservative management was recommended with strenuous exercise restrictions. The patient fared well during 12 months of follow-up after discharge. Discussion Hybrid cardiac imaging-guided conservative management including exercise restriction appears justifiable in such middle-aged adults with R-ACAOS accompanied by suspected angina in absence of ischaemia in stress-induced tests (TMT or SPECT), despite high-risk anatomical features of an IAC and slit-like orifice being present.

Background: Diabetic peripheral neuropathy (DPN) characterized by nerve damage is a common and disabling chronic microvascular complication in patients with type 2 diabetic mellitus (T2DM), affecting at least half of patients diagnosed with T2DM. Unfortunately, the current treatment for DPN is not ideal. Traditional Chinese medicine (TCM), with a unique theoretical system, has made outstanding contributions in the treatment of T2DM and related complications. Mudan granule, a Chinese patent medicine, has been previously validated that could ameliorate the symptoms, promote nerve tissue repair, increase nerve conduction velocity (NCV) in patients with DPN. However, the previous studies are of variable quality, which limits the clinical application of Mudan granule. Therefore, we designed a double-blind, randomized, placebo-controlled, parallel-arm, multi-center trial to estimate the safety and efficacy of Mudan granule in conjunction with methylcobalamin in individuals suffering from type 2 diabetic peripheral neuropathy.Methods: This work is conducted as a 14-center, double-blind, randomized, placebo-controlled, parallel-arm trial. In all, 402 subjects (aged 30–70 years) will be recruited and randomized in a 1:1 ratio to an intervention group (n = 201; Mudan granule + methylcobalamin) and a control group (n = 201; placebo + methylcobalamin). Treatment is administered in 24 weeks cycles without any treatment interruption between cycles. Michigan Diabetic Neuropathy Score (MDNS) as the primary outcome will be evaluated at baseline, 12 weeks during the intervention period, and after 24 weeks of the intervention. Adverse events and safety assessments will be also documented. The analysis of all data will be carried out based on a predefined statistical analysis plan.Discussion: The outcomes from this study will offer important evidence regarding the safety and efficacy that Mudan granule can be used as an alternative and complementary therapeutic intervention in patients with type 2 diabetic peripheral neuropathy.Clinical trial registration: Registered at https://clinicaltrials.gov/. Trial registration number: NCT04711980. Registered January 2021.