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Background: Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. Methods: We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (

BackgroundPrevious studies found that Jinlida granules could significantly reduce blood glucose levels and enhance the low-glucose action of metformin. However, the role of Jinlida in the standard-reaching rate of blood glucose and improving clinical symptoms has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in type 2 diabetes (T2D) patients who experience clinical symptoms based on secondary analysis of a randomized controlled trial.MethodsData were analyzed from a 12-week, randomized, placebo-controlled study of Jinlida. The standard-reaching rate of blood glucose, the symptom disappearance rate, the symptom improvement rate, the efficacy of single symptoms, and the total symptom score were evaluated. The correlation between HbA1c and the improvement of clinical symptoms was analyzed.ResultsFor 12 weeks straight, 192 T2D patients were randomly assigned to receive either Jinlida or a placebo. The treatment group showed statistically significant differences in the standard-reaching rate of HbA1c < 6.5% (p = 0.046) and 2hPG (< 10 mmol/L, 11.1 mmol/L) (p < 0.001), compared with the control group. The standard-reaching rate of HbA1c < 7% (p = 0.06) and FBG < 7.0 mmol/L (p = 0.079) were not significantly different between the treatment and control groups. Five symptoms exhibited a statistical difference in symptom disappearance rate (p < 0.05). All the symptoms exhibited a significant difference in symptom improvement rate (p < 0.05). The mean change in total symptom score from baseline to week 12 was −5.45 ± 3.98 in the treatment group and −2.38 ± 3.11 in the control group, with statistically significant differences (p < 0.001). No significant correlations were noted between symptom improvement and HbA1c after 12 weeks of continuous intervention with Jinlida granules or placebo.ConclusionJinlida granules can effectively improve the standard-reaching rate of blood glucose and clinical symptoms of T2D patients, including thirst, fatigue, increased eating with rapid hungering, polyuria, dry mouth, spontaneous sweating, night sweat, vexing heat in the chest, palms, and soles, and constipation. Jinlida granules can be used as an effective adjuvant treatment for T2D patients who experience those symptoms.

Yu-Bin Liu,1 Lin Zhang,1 Xing-Chen Zhou,1 Ying Zhou,1 Yun Liu,1 Can Zheng,1 Xiao Xu,1 Pan-Pan Geng,1 Chun-Hua Hao,2 Zhuan-You Zhao,2 Chu-Tse Wu,1 Ji-De Jin1 1Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China; 2Center for Pharmacodynamic Research, Tianjin Institute of Pharmaceutical Research, Tianjin, 300462, People’s Republic of ChinaCorrespondence: Chu-Tse Wu; Ji-De Jin, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, People’s Republic of China, Tel +86 1086-68158312 ; +86 1086-66931425, Email wuct@bmi.ac.cn; jinjide505@163.comIntroduction: Recombinant neorudin (EPR-hirudin, EH) was developed through the addition of an EPR (Glu-Pro-Arg) peptide to the amino terminus of hirudin, which can be recognized and cut by coagulation factors XIa (FXIa) and/or Xa (FXa). In this study, the low-bleeding antithrombotic effects of EH were evaluated utilizing experimental models of thrombosis in rabbits and rats to provide a test basis for clinical trials.Methods: The bleeding risks of EH and hirudin were first compared in mice by the tail-clipping method, and then the antithrombotic activity of EH was investigated in a rabbit model of arteriovenous bypass thrombosis and a rat model of thrombotic cerebral infarction.Results: In mice, intravenous administration of EH at 1.5 mg/kg and 3 mg/kg did not affect the bleeding time compared with normal saline, while the administration of hirudin at 1.5 mg/kg prolonged the bleeding time by over 3 times the administration of normal saline. Furthermore, intravenous administration of EH had a significant dose-dependent inhibitory effect on the formation and development of arteriovenous bypass thrombosis and thrombotic cerebral infarction. Compared with an equimolar dose of hirudin, the antithrombotic effect of EH was similar, while the bleeding side effects were significantly attenuated. Moreover, when the antithrombotic effects were similar, EH had a shorter bleeding time and was associated with less bleeding than low molecular weight heparin (LMWH). EH had a therapeutic effect on thrombotic cerebral infarction without increasing the occurrence of cerebral hemorrhage.Conclusion: The findings from the preclinical animal models used in this study showed that EH could not only effectively inhibit thrombus formation but also reduce the risk of bleeding.Keywords: recombinant neorudin, hirudin, antithrombotic effect, bleeding

Objective. To explore the application of touching combined with intelligent interaction of voice and rhythm in the nursing of neonatal feeding intolerance and its effect on the quality of life. Methods. A total of 140 newborns with feeding intolerance treated in our hospital from April 2019 to April 2021 were selected. The patients were randomly divided into two groups: the control group and the study group. The control group received touch nursing and the study group received touch combined with intelligent interactive nursing mode of voice, music, and rhythm. The general data, feeding performance, feeding process, growth and development, feeding intolerance, total intestinal feeding, jaundice duration, hospital stay, and quality of life scores were compared between the two groups. Results. First of all, we compared the general data of the two groups. There was no significant difference in gestational age, sex, mode of delivery, birth weight, head circumference, body length, Apgar score, and other general data between the two groups. Second, we compared the feeding performance of the two groups. Before nursing, there was no significant difference between the two groups ( P > 0.05 ). After nursing, the feeding rate, milk intake ratio, and proficiency of the two groups increased, and the comparison between the two groups. The feeding rate, milk intake ratio, and proficiency of the study group were better than those of the control group. In terms of the feeding process of the two groups, the days of oral feeding, complete import feeding, feeding conversion, and indwelling gastric tube in the study group were lower than those in the control group ( P < 0.05 ). In terms of the growth and development of the two groups, the recovery time of birth weight in the study group was lower than that in the control group, and the growth of body weight, length, and head circumference at 14 days in the study group was higher than those in the control group. The feeding intolerance, the duration of jaundice, and the days of hospitalization in the study group were lower than those in the control group ( P < 0.05 ). Moreover, the feeding intolerance, the duration of jaundice, and the days of hospitalization in the study group were lower than those in the control group ( P < 0.05 ). Finally, we compared the scores of qualities of life between the two groups. The physiological function, psychological function, and social function of the study group were lower than those of the control group ( P < 0.05 ). The physiological function, psychological function, and social function of the study group were lower than those of the control group ( P < 0.05 ). Conclusion. The application of touching combined with phonetic rhythm intelligent interaction technology in the nursing of neonatal feeding intolerance can promote the faster development and maturity of neonatal gastrointestinal function, improve gastrointestinal motility, shorten the time of parenteral nutrition in newborns, achieve total enteral feeding faster, and promote neonatal growth and development, so as to shorten the duration of hospitalization, improve the tolerance of neonatal gastrointestinal feeding, and improve the quality of life.

Diabetic kidney disease (DKD) is more prevalent with an increase in diabetes mellitus. Oxidative stress is a major factor in the occurrence and progression of DKD. Defending against oxidative stress and restoring antioxidant defense might be key to preventing and treating DKD. The purpose of this article is to provide an explanation of how oxidative stress affects DKD, conduct a systematic review and meta-analysis on DKD, and examine the effect of antioxidants on the disease. An analysis of 19 randomized controlled trials showed that the use of antioxidants could reduce UAE (albumin excretion rate) in patients with DKD (SMD: − 0.31; 95% CI [− 0.47, − 0.14], I2 = 0%), UACR (urine albumin/creatinine ratio) (SMD: − 0.60; 95% CI [− 1.15, − 0.06], I2 = 89%), glycosylated hemoglobin (hbA1c) (MD: − 0.61; 95% CI [− 1.00, − 0.21], I2 = 93%) and MDA (malonaldehyde) (SMD:-1.05; 95% CI [− 1.87, − 0.23], I2 = 94%), suggesting that antioxidants seemed to have therapeutic effects in patients with DKD, especially in reducing proteinuria and hbA1c. The purpose of this study is to provide new targets and ideas for drug research and clinical treatment of DKD.

The stability assessment of a large power system in real-time is very necessary after it encounters fault. The paper proposes a new model (SVM-GDPSO) for assessing the large power system. In order to enhance SVM, taking tangent vector of power flow Jacobian (PFJ) as the goal of machine learning was used for improving the precision. Besides, particle swarm optimization (PSO) with Gaussian disturbance (GD) is taken for setting the key parameters of SVM, and metalearning was utilized to decrease the search space of PSO. The experiment on the standard test system of IEEE 118-bus demonstrated that this model could reflect the status of large power system in time. Besides, the method could locate the fault area and rank the fault level by the observation of critical bus. The proposed method has the reliability rate 97.22 %, which is superior to the back propagation neural network (BPNN) and SVM-GA, as well as determines the fault area with the success rate of 96.61 %.

Type 2 diabetes mellitus (T2DM), a chronic low-grade inflammatory disease with high morbidity and mortality, is a serious threat to public health. Previously we demonstrated that a traditional Chinese medicine formulation, Jiedu Tongluo Tiaogan Formula (JDTL), exerted a favorable hypoglycemic effect due to unknown molecular mechanisms involving interactions among JDTL compounds and various cellular components. This study aimed to explore JDTL mechanisms for alleviating hyperglycemia using an integrated strategy incorporating system pharmacology, bioinformatics analysis, and experimental verification. This strategy entailed initial elucidation of JDTL chemical composition using fingerprint analysis via high performance liquid chromatography (HPLC). Next, functions of putative shared target genes and associated pathways were deduced using GO and KEGG pathway enrichment and molecular docking analyses. Ultimately, targets associated with JTDL anti-T2DM effects were found to be functionally associated with biological functions related to lipopolysaccharide and cytokine receptor binding. These results implicated PI3K-Akt signaling pathway involvement in JDTL anti-T2DM effects, as this pathway had been previously shown to play significant roles in glucose and lipid metabolism-related diseases. Furthermore, addition of JDTL to INS-1 and HepG2 cell cultures stimulated cellular mRNA-level and protein-level expression leading to enhanced production of IRS1, Akt, and PI3K. In summary, here JDTL bioactive ingredients, potential targets, and molecular mechanisms underlying JDTL anti-T2DM effects were identified using a multi-component, multi-target, and multi-channel analytical approach, thus providing an important scientific foundation to facilitate development of new drugs mechanistic strategies for preventing and treating T2DM.

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

Diabetic kidney disease (DKD) is one of the major public health problems in society today. It is a renal complication caused by diabetes mellitus with predominantly microangiopathy and is a major cause of end-stage renal disease (ESRD). Autophagy is a metabolic pathway for the intracellular degradation of cytoplasmic products and damaged organelles and plays a vital role in maintaining homeostasis and function of the renal cells. The dysregulation of autophagy in the hyperglycaemic state of diabetes mellitus can lead to the progression of DKD, and the activation or restoration of autophagy through drugs is beneficial to the recovery of renal function. This review summarizes the physiological process of autophagy, illustrates the close link between DKD and autophagy, and discusses the effects of drugs on autophagy and the signaling pathways involved from the perspective of podocytes, renal tubular epithelial cells, and mesangial cells, in the hope that this will be useful for clinical treatment.

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

Background: Acute bronchitis (AB) is a common disease in pediatrics. Prolonged AB may develop into chronic bronchitis. Bronchitis caused by the influenza virus can lead to severe hypoxia or insufficient ventilation, causing great harm to patients and increasing the burden on children and society. Presently, there is no specific treatment for AB except symptomatic supportive treatment. It is urgent to find an effective treatment for AB. Jinzhen Oral Liquid (JZOL) has been found to have a broad spectrum of anti-inflammatory and antiviral effects in previous clinical and basic studies and has a good effect on AB in children. However, the large-sample, randomized, double-blind, head-to-head, evidence-based studies are lacking. The purpose of this protocol is to evaluate the efficacy, safety, and mechanism of JZOL in the treatment of AB in children.Methods: This is a randomized, double-blind, parallel-controlled multi-center clinical trial. The sample size is 500 participants in the intervention group and the control group respectively, with a total of 1000 participants. They will be recruited by 10 hospitals in China. The Intervention group takes JZOL and Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution (AHCHOS) placebo, while the control group receives AHCHOS and JZOL placebo. The dosage of the two drugs varies according to age and weight. The medication lasts for 7 days. The disappearance time of cough is adopted as the primary outcome. Quality control will be carried out at every stage of data management and processing to ensure that all data are reliable and processed correctly. SAS is used for statistical analysis. Intention-to-treat analysis will be carried out in this trial. All statistical tests are conducted using a two-sided test, and p Discussion: We hypothesized that children with AB could get good health benefits from JZOL. This study not only evaluates the clinical efficacy and safety of JZOL but also conducts metagenomics analysis and metabolomics analysis of feces and saliva of participants to study the mechanism of JZOL against AB. Therefore, this protocol evaluates the efficacy, safety, and mechanism of JZOL from a comprehensive perspective, so as to obtain a more solid evidence chain, which will enhance the credibility of the evidence. If successful, this study will provide a high-level evidence-based reference for the treatment of AB in children and future relevant studies.

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/.

BackgroundDiabetic retinopathy (DR), one of the commonest microvascular complications in diabetic patients, is featured by a series of fundus lesions. Conventional Western medicine therapies for DR are always with modest treatment outcome. This paper is to assess the ocular fundus signs, vision and safety of Chinese patent medicines (CPMs) as an add-on treatment for DR.Method7 electronic databases were searched to determine eligible trials. Randomized controlled trials (RCTs) of non-proliferative diabetic retinopathy (NPDR) in which the intervention group received CPMs combined with calcium dobesilate (CD), and the control group received only CD were included for analysis. Two reviewers extracted the data independently. Results expressing as mean differences (MD) and relative risks (RR) were analyzed with a fixed-effects or random-effects models.Results19 RCTs involved 1568 participants with 1622 eyes met our inclusion criteria. The results suggested that compared with CD alone, CPMs plus CD for NPDR was superior at reducing the microaneurysm volume (MD -3.37; 95% confidence interval [CI], -3.59 to -3.14), microaneurysm counts (MD -2.29; 95%CI -2.97 to -1.61), hemorrhage area (MD -0.79; 95%CI -0.83 to -0.75), and macular thickness (MD -59.72; 95%CI -63.24 to -56.20). Participants in CPMs plus CD group also achieved a better vision. No obvious adverse events occurred.ConclusionCPMs as an add-on therapy for NPDR have additional benefits and be generally safe. This meta‐analysis demonstrated that CPMs combined with CD could improve retinal microaneurysm, hemorrhage, macular thickness, visual acuity, fasting blood glucose (FBG), and glycosylated hemoglobin (HbAlc) compared with CD alone. Further studies are needed to provide more conclusive evidence.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021257999.

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.

BackgroundDiabetic renal fibrosis (DRF) is an irreversible renal pathological change in the end-stage of diabetic kidney disease (DKD), which plays a significant role in the development and deterioration of the disease. However, data for bibliometric analysis of renal fibrosis in DKD is currently missing. This study aimed to provide a comprehensive and visualized view of DRF research and lay the foundation for further studies.Materials and MethodsFirstly, the data was collected from the Web of Science Core Collection (WoSCC) database. Secondly, the Web of Science analytic tool was performed to analyze publication years, authors, countries/regions, organizations, and citation frequency. Finally, CiteSpace was employed to construct a visualization bibliometric network to reveal the emerging trends and hotspots of DRF.ResultsA total of 3,821 publications from 1985 to 2020 were included in this study. The number of publications has maintained a growth trend since 2003. Cooper is the most prolific author in this field, and the American Journal of Physiology-Renal Physiology ranking as first place compared with other journals. In terms of the number of publications, China contributed the most to DRF. Monash University is the organization that published the most papers. The top 5 clusters of keyword co-appearance are “chronic kidney disease”, “primary biliary cirrhosis”, “receptor”, “TGF-beta”, “renal tubulointerstitium”. The top 5 clusters of reference co-citation are “microRNAs”, “bone morphogenetic protein”, “hypertrophy”, “glomerulosclerosis”, “diabetic kidney disease”. The strongest citation burst of keyword is “diabetic kidney disease” and the strongest burst of cited reference is “Meng, 2016”.ConclusionsThe present study analyzed the research hotspots, Frontiers, and development trend of DRF and have important implications for future research.

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 global greenhouse gas emitted from shipping activities is one of the factors contributing to global warming; thus, there is an urgent need to mitigate the adverse effect of climate change. One of the key strategies is to build a vibrant maritime industry with the use of innovation and digital technologies as well as intelligent systems. The digitization of the shipping industry not only provides a competitive edge to the shipping business model but also enhances ship operational and energy efficiency. This review paper focuses on the big data analytics and machine learning applied to harbour craft vessels with the aim to achieve fuel efficiency. The paper reviews the telemetry system requires for the digitalization of harbour craft vessels, its challenges in installation, the vessel monitoring and data transmission system. The commonly used methods for data cleaning are also presented. Last but not least, the paper considers two types of the machine learning systems, i.e., supervised and unsupervised machine learning systems. The multi-linear regression and hidden Markov model for supervised machine learning system and the artificial neural network, grey box model and long short-term memory model for unsupervised machine learning are discussed, and their pros and cons are presented.

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.

Food is people’s primal want. A reasonable diet and healthy food not only provide nutrients for human growth but also contribute to disease prevention and treatment, while following an unhealthy diet can lead to an increased risk of many diseases, especially metabolic disorders, such as diabetes. Nature is enriched with different food sources, and it seems that purely natural products are more in line with the current concept of health, which enhance the formation of the notion that “Food/Diet Supplements from Natural Sources as a Medicine.” As a delicious fruit, the medicinal values such as anticancer, antibacterial, antioxidation, and antiglycating properties of lychee have been found. Lychee (Litchi in Chinese) is a subtropical fruit plant belonging to the family Sapindaceae. It has been widely cultivated in warm climates worldwide, particularly in China, for thousands of years. In recent years, various phytochemical components such as quercetin, procyanidin A2, and (2R)-naringenin-7-O-(3-O-αL-rhamnopyranosyl-β-D-glucopyranoside) have been identified in a lychee seed, which may lend a lychee seed as a relatively safe and inexpensive adjuvant treatment for diabetes and diabetic complications. In fact, accumulating evidence has shown that lychee seed, lychee seed extracts, and related compounds have promising antihyperglycemic activities, including improving insulin resistance, anti-inflammatory effect, lipid regulation, neuroprotection, antineurotoxic effect, and renoprotection effect. In this review, we summarized publications on antiglycemic effects and mechanisms of lychee seed, lychee seed extracts, and related compounds, which included their efficacies as a cure for diabetes and diabetic complications in cells, animals, and humans, attempting to obtain a robust evidence basis for the clinical application and value of lychee seed.

In terms of treatment, a particularly targeted drug is needed to combat the COVID-19 pandemic. Although there are currently no specific drugs for COVID-19, traditional Chinese medicine(TCM) is clearly effective. It is recommended that through data analysis and mining of TCM cases (expert experience) and population evidence (RCT and cohort studies), core prescriptions for various efficacy can be obtained. Starting from a multidimensional model of regulating immunity, improving inflammation, and protecting multiple organs, this paper constructs a multidimensional model of targeted drug discovery, integrating molecular, cellular, and animal efficacy evaluation. Through functional activity testing, biophysical detection of compound binding to target proteins, multidimensional pharmacodynamic evaluation systems of cells (Vero E6, Vero, Vero81, Huh7, and caca2) and animals (mice infected with the new coronavirus, rhesus macaques, and hamsters), the effectiveness of effective preparations was evaluated, and various efficacy effects including lung moisturizing, dehumidification and detoxification were obtained. Using modern technology, it is now possible to understand how the immune system is controlled, how inflammation is reduced, and how various organs are protected. Complete early drug characterization and finally obtain effective targeted TCM. This article provides a demonstration resource for the development of new drugs specifically for TCM.

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.

Graphical abstract Abbreviation: SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus Disease 2019., Highlights • TCM could reduce the all-cause mortality in COVID-19 patients. • TCM could inhibit virus replication and transcription of SARS-CoV-2. • TCM can attenuate the cytokine storm and immune deficiency caused by the SARS-CoV-2., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus causing serious human disease to spread across the world in the past 20 years, after SARS and Middle East respiratory syndrome. As of mid-September 2020, more than 200 countries and territories have reported 30 million cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, including 950,000 deaths. Supportive treatment remains the mainstay of therapy for COVID-19. The World Health Organization reported that four candidate drugs, including remdesivir, are ineffective or have little effect on COVID-19. According to China News, 90 % of Chinese patients with COVID-19 use traditional Chinese medicine (TCM), with an effectiveness rate of 80 %, and no deterioration in patient condition. We have compiled the direct evidence of TCM treatment for COVID-19 as of December 31, 2020. We describe the advantages of TCM in the treatment of COVID-19 based on clinical evidence and the required methods for its clinical use. TCM can inhibit virus replication and transcription, prevent the combination of SARS-CoV-2 and the host, and attenuate the cytokine storm and immune deficiency caused by the virus infection. The cooperation of many countries is required to establish international guidelines regarding the use of TCM in patients with severe COVID-19 from other regions and of different ethnicities. Studies on the psychological abnormalities in patients with COVID-19, and medical staff, is lacking; it is necessary to provide a complete chain of evidence to determine the efficacy of TCM in the related prevention, treatment, and recovery. This study aims to provide a reference for the rational use of TCM in the treatment of COVID-19.