ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:To explore the effects of Sangqiao Qingfei Prescription combined with Western medicine conventional therapy with mechanical ventilation on lung function and airway inflammation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) respiratory failure; To evaluate clinical efficacy.Methods:A randomized controlled trial study was conducted. Totally 90 AECOPD patients with respiratory failure in our hospital from January 2020 to December 2022 were selected as the observation subjects. They were divided into two groups using a random number table method, with 45 cases in each group. The control group received mechanical ventilation treatment, while the observation group received Sangqiao Qingfei Prescription on the basis of the control group. Both groups were treated for 2 weeks. TCM syndrome scoring was performed before and after treatment, and the time of successful withdrawal from the machine was recorded; a blood gas analyzer was used to detect PaO 2, PaCO 2, blood oxygen saturation (SaO 2) and pH values; the plateau pressure (Pplat), peak airway pressure (Ppeak), airway resistance (Raw) and dynamic lung compliance (Cdyn) were recorded during the ventilator; a pulmonary function meter was used to measure respiratory rate (RR), maximum expiratory flow (PEF), FVC, FEV1, and the percentage of FEV1 to the estimated value (FEV1% estimated value); serum CRP, TNF-α, and Procalcitonin (PCT) were detected using ELISA method. Clinical efficacy was evaluated. Results:During the treatment period, there were no cases of detachment in both groups. The mechanical ventilation time in the observation group was (7.16 ± 0.69) d, while in the control group it was (9.88 ± 1.04) d, with statistical significance ( t=14.62, P<0.001); after treatment, the main symptom, secondary symptom scores, and total scores of the observation group were lower than those in the control group ( t values of 13.43, 18.53, 31.21, P<0.001); the PaO 2 [(79.16 ± 7.42) mmHg vs. (67.49 ± 6.88) mmHg, t=8.24], SaO 2 [(95.15 ± 9.93)% vs. (84.59 ± 9.48)%, t=5.16], and pH value (7.35 ± 0.23 vs. 7.26 ± 0.16, t=2.16) in the observation group were higher than those in the control group ( P<0.01 or P<0.05), while PaCO 2 [(49.89 ± 3.65) mmHg vs. (62.39 ± 4.27) mmHg, t=14.93] was lower than that of the control group ( P<0.01); after treatment in the observation group, Pplat [(15.31 ± 2.51) cmH 2O vs. (17.53 ± 2.02) cmH 2O, t=4.62], Ppeak [(22.43 ± 3.16) cmH 2O vs. (25.78 ± 3.17) cmH 2O, t=5.02], Raw [(18.96 ± 3.86) cmH 2O/(S?L) vs. (24.29 ± 4.29) cmH 2O/(S?L), t=6.20] were lower than those in the control group ( P<0.01), Cdyn [(34.53 ± 3.35) cmH 2O/(S?L) vs. (30.27 ± 3.87) cmH 2O/(S?L), t=5.58] was higher than the control group ( P<0.01); the RR [(19.25 ± 2.43) times/min vs. (23.49 ± 3.07) times/min, t=7.26] in the observation group was lower than that of the control group ( P<0.01), PEF [(4.99 ± 0.40) L/s vs. (4.03 ± 0.34) L/s, t=12.27], FVC [(3.04 ± 0.20) L vs. (2.14 ± 0.22) L, t=20.31], FEV1 [(2.83 ± 0.20) L vs. (2.16 ± 0.13) L, t=18.84], FEV1% estimated value [(42.23 ± 4.66)% vs. (36.43 ± 5.09)%, t=5.64] were higher than those in the control group ( P<0.01); serum CRP, IL-6, TNF-α and PCT in the observation group were lower than those in the control group ( t values were 18.13, 13.36, 15.97, 30.67, P<0.01). The total effective rate of the observation group was 93.33% (42/45), while that of the control group was 77.78% (35/45), with statistical significance ( χ2=4.41, P=0.036). Conclusion:The combination of Sangqiao Qingfei Prescription and conventional Western medicine treatment with mechanical ventilation can effectively improve lung ventilation function, reduce inflammatory cytokine levels, alleviate inflammatory reactions, and improve clinical efficacy in AECOPD patients with respiratory failure.

Objective To explore the predictive value of serum cathepsin S(CTSS),progranulin(PGRN)and chemo-kine ligand 12(CXCL12)for acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 202 patients with COPD who were admitted to the Tongling Municipal Hospital from January 2020 to February 2023 were selected as the research subjects.The patients were divided into an acute exacerbation group(n=64)and a non-acute exacerbation group(n=138)according to whether acute exacerbation occurred.Clinical data such as serum CTSS,PGRN and CXCL12 levels,age,gender,body mass index(BMI),disease course,smoking history,forced expiratory volume in one second/forced vital capacity ratio(FEV1％),and COPD assessment test(CAT)score in the stable period were collected.Univariate analysis was made to compare the differences in relevant indicators between the two groups,and multivariate logistic regression analysis was made to identify the independent risk factors for acute exacerbation in COPD patients.The Pearson correlation method was used to analyze the correlation between serum CTSS,PGRN,CXCL12 levels and FEV1％,CAT score.Relative risk analysis was used to evaluate the influence of different CTSS,PGRN and CXCL12 levels on acute exacerbation in COPD patients.The predictive efficacy of serum CTSS,PGRN and CXCL12 levels on acute exacerbation in COPD patients was evaluated by receiver operating characteristic(ROC)curve.Results Univariate analysis showed that there was no significant difference in age,sex,BMI and disease course of patients between the two groups(P＞0.05),while there were significant differences in the propor-tion of patients with smoking history,FEV1％,CAT score,and serum CTSS,PGRN and CXCL12 levels between the two groups(P＜0.05).Multivariate logistic regression analysis showed that elevated serum CTSS,PGRN and CXCL12 levels were risk factors for acute exacerbation in COPD patients(P＜0.05).There were significant differences in serum CTSS,PGRN and CXCL12 levels among patients with different FEV1％and CAT scores(P＜0.05).Pearson correlation analysis showed that serum CTSS,PGRN and CXCL12 levels were negatively correlated with FEV1％and positively correlated with CAT score(P＜0.05).Risk analysis showed that the risk of acute exacerbation in COPD patients with high serum CTSS,PGRN and CXCL12 levels was 2.089 times[95％confidence interval(CI):1.341-3.253],2.294 times(95％CI:1.363-3.862)and 2.359 times(95％CI:1.459-3.815)of the COPD patients with low serum CTSS,PGRN and CXCL12 levels.ROC analysis indica-ted that the area under the curve for predicting the risk of acute exacerbation in COPD patients based on serum CTSS,PGRN and CXCL12 levels alone was 0.780,0.811 and 0.755,respectively;the area under the curve for predicting the risk of acute exacerbation in COPD patients based on the combination of serum CTSS,PGRN and CXCL12 levels was 0.923.Conclusion Serum CTSS,PGRN and CXCL12 levels are risk factors for acute exacerbation of COPD.Abnormal elevation of serum CTSS,PGRN and CXCL12 levels can significantly increase the risk of acute exacerbation of COPD.The combination of serum CTSS,PGRN and CXCL12 levels is more effective in predicting the risk of acute exacerbation of COPD.

Objective:To investigate the role and mechanism of microRNA (miR)-4472 targeting PIN1 in regulating the nuclear factor kappa B (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE).Methods:Between January 2022 and January 2024, sixty Sprague-Dawley rats were randomly assigned to six groups at The Second Hospital of Jiaxing using a random number table method: a normal control group, an HIE model group, an inhibition control group, a miR-4472 inhibition group, a miR-4472 inhibition + interference control group, and a miR-4472 inhibition + PIN1 interference group, with ten rats in each group. There was no significant difference in body mass among the six groups (all P > 0.05). Rat models of HIE were established using the Rice-Vannucci method. Behavioral performance was assessed using the Morris water maze test, while neurological function was evaluated using the Longa scoring method. Apoptosis was detected using the TUNEL assay, and the expression of NF-κB and STAT3 protein was measured using Western blot analysis. Results:Compared with the HIE model group, the miR-4472 inhibition group and the miR-4472 inhibition + interference control group showed a shortened escape latency, while the miR-4472 inhibition + PIN1 interference group exhibited an extended escape latency (all P < 0.05). The number of platform crossings in the miR-4472 inhibition + PIN1 interference group [(2.13 ± 0.54) times] was significantly lower than that in the HIE model group [(3.56 ± 0.71) times], the inhibition control group [(3.61 ± 0.87) times], the miR-4472 inhibition group [(5.47 ± 1.29) times], and the miR-4472 inhibition + interference control group [(5.58 ± 1.32) times] ( t = 5.07, 4.57, 7.55, 7.65, all P < 0.05). The Longa score in the miR-4472 inhibition + PIN1 interference group [(3.03 ± 0.30) points] was significantly lower than that in the HIE model group [(2.45 ± 0.54) points], the inhibition control group [(2.38 ± 0.69) points], the miR-4472 inhibition group [(1.27 ± 0.46) points], and the miR-4472 inhibition + interference control group [(1.29 ± 0.51) points] ( t = 2.97, 2.73, 10.13, 9.30, all P < 0.05). The apoptosis rate of hippocampal neurons in the miR-4472 inhibition + PIN1 interference group [(25.34 ± 6.16)%] was significantly lower than that in the HIE model group [(18.42 ± 5.46)%], the inhibition control group [(17.95 ± 4.38)%], the miR-4472 inhibition group [(8.89 ± 2.10)%], and the miR-4472 inhibition + interference control group [(9.13 ± 2.57)%] ( t = 2.97, 2.73, 10.13, 9.30, all P < 0.05). Compared with the HIE model group, the miR-4472 inhibition group and the miR-4472 inhibition + interference control group exhibited decreased gray values of NF-κB and STAT3 protein, while the miR-4472 inhibition + PIN1 interference group showed increased gray values of NF-κB and STAT3 protein (all P < 0.05). Conclusion:miR-4472 targets and regulates PIN1, which contributes to HIE injury through the activation of the NF-κB/STAT3 signaling pathway.

Japan is one of the main trading partners for the import and export of experimental animals in China,and its quarantine and supervision policies for the import and export of experimental animals are very detailed and strict.This article takes experimental dogs,cats,and monkeys as examples to provide an in-depth analysis of the quarantine and supervision policies for the main experimental animals exported to Japan.At the same time,it reflects on the current laws and regulations,import and export management method,standards,biosafety,breeding and management status,as well as the import and export business status of experimental animals in China.Suggestions are provided in improving the laws and regulations,import and export management method,ensuring national biosafety,improving the management level of experimental animal breeding,and promoting the import and export trade of experimental animals,in order to provide reference for comprehensively improving the production,use,and breeding management level of experimental animals in China and strengthening the trade between China and Japan.

Objective To evaluate the effectiveness of internet-based decision aids(DA)in colorectal cancer screening.Methods Randomized controlled trials of efficacy of internet-based DA in colorectal cancer screening were searched by computer from CNKI,Wanfang Data,VIP,CBM,PubMed,the Cochrane Library,Embase and Web of Science.The retrieval period was from the establishment of the database to June 2023.Descriptive analysis was used to analyze the main contents and summarize their clinical application effects.Results A total of 12 literatures were included,including 6038 subjects,of which 3089 were in experimental group and 2949 were in control group.The results showed that the contents of internet-based DA mainly included basic information support,benefits and risks of colorectal cancer screening,and clarification of patients'personal values.It could help patients enhance screening willingness,improve informed decision-making ability,reduce decision-making conflicts,and promote the positive role of patients in decision-making.Patients have higher satisfaction with internet-based DA.Conclusion Internet-based DA has shown positive results in the application of colorectal cancer screening,and has unique advantages over the traditional paper version of the manual,but it still has certain limitations.In the future,we can learn from the relevant theoretical achievements of foreign decision-making assistance,research and develop a more comprehensive DA for colorectal cancer screening combined with China's national conditions.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled