BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

BACKGROUND:Stem cells can promote nerve regeneration,repair damaged nerves,inhibit inflammation and apoptosis of nerve cells,and provide a new way for the treatment of Alzheimer's disease. OBJECTIVE:To make a bibliometrical analysis of the articles on stem cell therapy for Alzheimer's disease published internationally from 2004 to 2023,in order to reveal the research hotspot and trend of stem cell therapy for Alzheimer's disease. METHODS:From the Web of Science Core Collection database,by using Excel,VOSviewer,and Citespace software,the annual number of publications,countries,institutions,journals/co-cited journals,authors,and keywords of articles related to stem cells and Alzheimer's disease published from January 1,2004 to October 31,2023 were visually analyzed. RESULTS AND CONCLUSION:A total of 3 521 core papers were included,and the number of published papers increased year by year.The United States is the country with the most papers.Harvard Medical School is the most prolific institution.Maiese kenneth is the author with the most papers.International Journal of Molecular Sciences has the most papers in this field.The journal PLoS One published the most citations.At present,the field of stem cell therapy for Alzheimer's disease focuses on pathophysiological mechanism and animal experimental research,and"neurogenesis","oxidative stress","extracellular vesicles",and"mesenchymal stem cells"are the research trends in this field.Stem cell therapy for Alzheimer's disease has broad prospects.In the future,exchanges and cooperation between institutions and authors should be strengthened to further explore the main mechanism of stem cell therapy for Alzheimer's disease,solve possible clinical problems such as immune rejection,effectiveness,and safety,and further tap the potential of stem cells in the treatment of Alzheimer's disease.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

On the premise of respecting the objective law of the occurrence and development of traditional Chinese medicine（TCM） dispensing granules， relevant national departments have gradually formed the research and formulation ideas of national drug standards for dispensing granules based on the experiences and lessons learned in the development process of quality standards， as well as the formation mechanism of national standards for dispensing granules. This has certain reference significance for the formulation path of TCM quality standards. Combined with the general situation of the published standards and specific cases， the research concepts of the national standards for dispensing granules were analyzed and summarized in this paper， and the analysis of the technical characteristics of the issued national standards was focused， including the introduction of standard decoction， the overall quality control of TCM， the whole process quality control and other research ideas. At the same time， it summarized the industry common problems in the research and development process of national standards for dispensing granules， such as the source and process control of medicinal materials， and strived to solve them together， encouraging the demonstration and application of new technological means in the field of TCM dispensing granules. Finally， based on the literature analysis， the shortcomings of the current national standards were discussed， and relevant suggestions were put forward to further improve the national standards for dispensing granules. Through the overall analysis， it is helpful to comprehensively understand the technical characteristics of the national standards for TCM dispensing granules， and provide reference for the scientific exploration and practice of quality control methods for TCM.

ObjectiveTo identify the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the health check-up population， and to perform stratified management of patients with the low， medium， and high risk of advanced fibrosis based on noninvasive fibrosis scores. MethodsA cross-sectional study was conducted among 3 125 individuals who underwent physical examination in Beijing Physical Examination Center from December 2017 to December 2019， and they were divided into MAFLD group with 1 068 individuals and non-MAFLD group with 2 057 individuals. According to BMI， the MAFLD group was further divided into lean MAFLD group （125 individuals with BMI<24 kg/m²） and non-lean MAFLD group （943 individuals with BMI≥24 kg/m²）. Indicators including demographic data， past history， laboratory examination， and liver ultrasound were compared between groups. Fibrosis-4 （FIB-4） score， NAFLD fibrosis score （NFS）， aspartate aminotransferase-to-platelet ratio index （APRI）， and BARD score were calculated for the patients in the MAFLD group to assess the risk of advanced fibrosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influence of each indicator in MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-9.758， P<0.05）， proportion of male patients （χ²=137.555， P<0.05）， and levels of body weight （Z=-27.987， P<0.05）， BMI （Z=-32.714， P<0.05）， waist circumference （Z=-31.805， P<0.05）， hip circumference （Z=-26.342， P<0.05）， waist-hip ratio （Z=-28.554， P<0.05）， alanine aminotransferase （ALT） （Z=-25.820， P<0.05）， aspartate aminotransferase （AST） （Z=-16.894， P<0.05）， gamma-glutamyl transpeptidase （GGT） （Z=-25.069， P<0.05）， alkaline phosphatase （Z=-12.533， P<0.05）， triglyceride （Z=-27.559）， total cholesterol （Z=-7.833， P<0.05）， low-density lipoprotein cholesterol （LDL-C） （Z=-8.222， P<0.05）， and uric acid （UA） （Z=-20.024， P<0.05）， as well as a significantly higher proportion of patients with metabolic syndrome （MetS） （χ²=578.220， P<0.05）， significantly higher prevalence rates of hypertension （χ²=241.694， P<0.05）， type 2 diabetes （χ²=796.484， P<0.05）， and dyslipidemia （χ²=369.843， P<0.05）， and a significant reduction in high-density lipoprotein cholesterol （HDL-C） （Z=23.153， P<0.001）. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=1.45， 95% confidence interval ［CI］： 1.203‍ ‍—‍ ‍1.737）， ALT （OR=1.05， 95%CI： 1.046‍ ‍—‍ ‍1.062）， LDL-C （OR=1.23， 95%CI： 1.102‍ ‍—‍ ‍1.373）， and comorbidity with MetS （OR=5.97， 95%CI： 4.876‍ ‍—‍ ‍7.316） were independently associated with MAFLD. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.736， P<0.05） and HDL-C （Z=2.679， P<0.05） and significant reductions in the proportion of male patients （χ²=28.970， P<0.05）， body weight （Z=-14.230， P<0.05）， BMI （Z=-18.188， P<0.05）， waist circumference （Z=-13.451， P<0.05）， hip circumference （Z=-13.317， P<0.05）， ALT （Z=-4.519， P<0.05）， AST （Z=-2.258， P<0.05）， GGT （Z=-4.592， P<0.05）， UA （Z=-4.415， P<0.05）， the proportion of patients with moderate or severe fatty liver disease or MetS （χ²=42.564， P<0.05）， and the prevalence rates of hypertension （χ²=12.057， P<0.05） and type 2 diabetes （χ²=3.174， P<0.05）. Among the patients with MAFLD， 10 patients （0.9%） had an FIB-4 score of >2.67， 4 patients （0.4%） had an NFS score of >0.676， 8 patients （0.7%） had an APRI of >1， and 551 patients （51.6%） had a BARD score of ≥2. ConclusionThere is a relatively high prevalence rate of MAFLD among the health check-up population in Beijing， but with a relatively low number of patients with a high risk of advanced fibrosis， and such patients need to be referred to specialized hospitals for liver diseases.

As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.