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.

Objective:To investigate the effect of theta-transcranial alternating current stimulation(θ-tACS)over the frontal-parietal cortex on working memory(WM)performance under different postural conditions(sitting and stand-ing)in healthy adults. Method:The study was a randomized,crossover,double-blind design.Sixteen healthy adults received tACS or sham stimulation in random order,with at least 72 hours interval between two sessions.Seven electrodes were placed in the left frontoparietal critical brain region with 6Hz for 21 mins.The sham stimulation used the same stimulation time and frequency as tACS group,but only 1 minute of stimulation(30s at the beginning and 30s at the end of the stimulation).WM performance was assessed before and immediately after stimulation,in-cluding accuracy,reaction time and inverse efficiency scores.Wilcoxon rank sum tests were used to observe between-and within-group differences on WM performance. Result:Fifteen participants completed the experiment and there were no significant differences in side effects be-tween two groups.There was a significant improvement in reaction time and inverse efficiency scores for sit-ting WM as well as reaction time for standing WM after the frontoparietal θ-tACS(P＜0.05).There was a trend towards improvement in inverse efficiency scores for standing WM(P=0.057),while there was no signif-icant difference in accuracy,reaction time and inverse efficiency scores of WM during the sitting and standing conditions in the sham stimulation(all P＞0.05). Conclusion:Frontoparietal θ-tACS can improve WM performance in both sitting and standing postures.This helps healthy adults cope with real-life multitasking cognitive activities and has important practical application value.

AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

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.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.

Primary hypotension is a common and frequently occurring blood vessel disease,characterized by insidious onset,lingering condition,complex etiology,and diverse symptoms.Its pathogenesis is primarily characterized by deficiency,and its onset involves multiple zang-fu organs.The"yang transforming qi and yin shaping up body"theory is derived from the Huangdi Neijing.This theory summarizes the fundamental laws of the movement and changes in yin and yang.From this perspective,the paper hypothesizes that the basic pathogenesis of primary hypotension stems from an insufficiency of yang in transforming qi and a malfunction of yin in shaping up body.The essence of the condition lies in an overall yang deficiency that fails to provide warmth and transformation,coupled with qi deficiency,which cannot control and regulate bodily functions.This leads to poor blood circulation and inadequate protection,causing yin to malfunction in forming the physical components of the body.As a result,normal physiological functions of the zang-fu organs are disrupted,the production of beneficial physiological substances is obstructed,and metabolic waste products accumulate.The primary therapeutic approach should be focused on tonifying qi and ascending yang;tonifying qi will provide the impetus for blood circulation,whereas ascending yang will facilitate yang transformation qi.The zang-fu organs should also be protected and nourished to ameliorate the internal environment of yang deficiency and yin excess,as well as to eliminate pathological product accumulation to dredge the channels of blood circulation.Using the"yang transforming qi and yin shaping up the body"theory to guide the treatment of primary hypotension can help deepen the understanding of the pathogenesis of this disease and broaden the clinical diagnosis and treatment strategies.