This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Root rot severely restricts the sustainable development of Astragalus membranaceus var. mongholicus (AMM) industry. Resistance breeding is an economical and environmentally safe way to manage the disease and its key lies in the obtaining of resistance indicators. This study aimed to quickly and accurately screen the resistance-related (RR) metabolites so as to provide reference for the screening of indicators of AMM breeding for resistance. LC-MS-based targeted metabolomics and real-time quantitative PCR technology were employed, in combination with multivariate statistical analysis, in analyzing the dynamic changes of phenylpropanoid metabolites in AMM in response to root rot pathogen Fusarium solani (FS) infection and identifying the differential metabolites. The LC-MS method established showed high sensitivity; each metabolite had a good linear relationship (R² ≥ 0.968 9) in the corresponding linear range of the respective standard curve; the recoveries and the relative standard deviations (RSDs) (n = 6) ranged from 70% to 107% and from 1.2% to 9.9%, respectively. Obvious disturbances were observed in the changes of the targeted metabolites in AMM infected by FS. These metabolites, compared with the mock-inoculated (CK) group, showed different up or down regulation with time series. Calycosin-7-O-β-D-glucoside, ononin, calycosin and formononetin were identified as differential metabolites, and they all belong to flavonoids. The first three compounds were significantly negatively correlated (r ≤ -0.97, P < 0.05) with the content of FS in the root of AMM. As potential RR metabolites, they are helpful in obtaining promising resistance indicators for AMM against FS infection.

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ²=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ²=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ²=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ²=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ²=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.
Humans ; Thyroid Nodule ; Thyroid Neoplasms/diagnosis* ; Carcinoma, Papillary/pathology* ; Ultrasonography/methods* ; Retrospective Studies

Hydrogen peroxide (H

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

The purpose was to discuss the infection status of human parainfluenza virus type 3 (HPIV-3) in children with acute respiratory tract infection(ARTI) in Qingdao, Shandong province, and to analyze the gene characteristics of HPIV-3 hemagglutinin-neuraminidase protein (HN). This study was a cross-sectional study. A total of 1 674 throat swab samples were collected randomly from children with ARTI, in the three hospitals (Qingdao Women and Children's Hospital, West Coast Branch of Affiliated Hospital of Qingdao University, Laoshan Branch of Affiliated Hospital of Qingdao University) from January 2018 to December 2019. Multiplex real-time fluorescence RT-PCR was performed to screen HPIV-3 positive specimens. For HPIV-3 positive specimens, nested PCR was used to amplify the full-length HN gene of HPIV-3. The HN gene was sequenced and compared with the representative strains of HPIV-3 in GenBank, and the phylogenetic tree was established. As results, this study collected 1 674 samples, in which there were 90 HPIV-3 positive samples showed and the detection rate was 5.37%. Among positive specimens, the number of samples from children under 6 years old was 88, accounting for 97.78%. HPIV-3 positive cases were mainly distributed in spring and summer. The full-length sequences of 44 HPIV-3 HN genes were obtained by nested PCR method. Sequence alignment and evolutionary analysis showed that the HPIV-3HN gene belonged to the C3a and C3b branches of C3 genotype, with 30 strains of subtype C3a and 14 strains of subtype C3b. The nucleotide and amino acid homology of the amplified 44 strains of the HPIV-3 HN gene in Qingdao were 97.0%-100.0% and 98.5%-100.0%, respectively. In conclusion, from 2018 to 2019, the C3a and C3b branches of HPIV-3 C3 genotype were circulating prevalent in Qingdao, Shandong province. HN gene variation rate was low, but showed certain regional characteristics in evolution.
Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Hemagglutinins ; Humans ; Neuraminidase ; Parainfluenza Virus 3, Human/genetics* ; Phylogeny ; Respiratory Tract Infections/epidemiology* ; Viral Proteins

This study is to explore the mechanism of Xueshuantong improving cerebral microcirculation disorder through the combination of network pharmacology and experimental validation in vivo. Structural formulas of main Panax notoginseng saponins, including notoginsenoside R1, and ginsenoside Rg1, Re, Rb1 and Rd were obtained from Pubchem website and their potential targets were predicted by Swiss Target Prediction database. Potential molecular targets of brain microcirculation disorder were acquired from OMIM and GeneCards database. The overlapped molecular targets between the drug and disease were analyzed. Protein interaction analysis and topology maps were constructed through the STRING online analysis platform and Cytoscape software. Core action targets were selected. GO function and KEGG pathway were analyzed by DAVID database. Immunohistochemical method was used to examine the expression of platelet endothelial cell adhesion molecule-1 (CD31) in the ischemic cortex of middle cerebral artery occlusion and reperfusion (MCAO/R) rats. The levels of mRNA and protein expressions of core action targets in MCAO/R model rats′ brain microvessels were verified by RT-qPCR and Western blot. Based on network pharmacology, 242 targets of Xueshuantong, 425 targets of brain microcirculation disorder, and 35 overlapped targets were obtained. The potential key targets of Xueshuantong, protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), caspase 3 (CASP3), matrix metallopeptidase 9 (MMP-9), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), signal transducer and activator of transcription 3 (STAT3) involved in the alleviation of cerebral microcirculation disorder were obtained by setting degree and betweenness centrality as screening parameters. Xueshuantong at the dose of 48 mg·kg^-1 was shown to significantly improve the injury of neurological behaviors, as well as the density and morphology of microvessels of MCAO/R model rats. Xueshuantong could down-regulate the mRNA levels of AKT1, MMP-9, and STAT3, increase the protein expression levels of CD31, phosphorylated AKT and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the ratio of B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/Bax), but decrease the protein expression levels of MMP-9, cleaved caspase-3 and phosphorylated STAT3. In summary, Xueshuantong could improve ischemic cerebral microcirculation disorder and thereby reduce nerve damage in ischemia-reperfusion rats by regulating signaling pathways related with PI3K, AKT, MMP-9, STAT3 and caspase-3 in microvessels. The study strictly adhered to all ethical protocols that experimental animals should follow in the course of medical research.

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.
Medicine, Chinese Traditional ; China

OBJECTIVE: To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat). METHODS: With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups. RESULTS: A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001). CONCLUSION Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.
Acupuncture Points ; Adolescent ; Anti-Bacterial Agents/therapeutic use* ; Child ; Child, Preschool ; Cough/drug therapy* ; Diarrhea ; Humans ; Infant ; Infant, Newborn ; Pharyngitis/drug therapy*