With the continuous development of China's aging society and the prevalence of unhealthy lifestyles, the incidence of cardiovascular disease in China has been increasing in recent years. Among them, atrial fibrillation (AF) is the most common arrhythmia disease. In recent years, pulsed field ablation (PFA) has been continuously applied to AF treatment as a novel treatment. This paper first introduces the principle of PFA applied to AF treatment, and introduces the research progress of PFA in different directions, such as the comparison of different ablation methods, the study of physical parameters, the study of ablation area, the study of tissue specificity and clinical research. Then, the clinical prior research of PFA is discussed, including the use of simulation software to obtain the simulation effect of different parameters, the evaluation of ablation effect during animal research, and finally the current AF treatment. Various prior studies and clinical studies are summarized, and suggestions are made for the shortcomings found in the study of AF treatment and the future research direction is prospected.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

BACKGROUND:Stand-alone oblique lateral interbody fusion has a high rate of complications of fusion segment sink.Oblique lateral interbody fusion with posterior fixation can provide stable support,but intraoperative position changes and double incisions weaken the advantages of this technique.Oblique lateral interbody fusion combined with lateral plate fixation can achieve one-stage decompression in the same incision,while the lateral internal fixation provides stable support. OBJECTIVE:To analyze the short-term efficacy of oblique lateral interbody fusion combined with lateral plate fixation in the treatment of single-level lumbar degenerative disease. METHODS:The clinical data of 34 patients with single-level lumbar degenerative disease treated with oblique lateral interbody fusion combined with lateral plate fixation were collected from May 2020 to October 2022.Among them,14 were males and 20 were females aged from 41 to 72 years at the mean age of(58.6±9.9)years.There were 11 cases of lumbar spondylolisthesis(Ⅰ°),7 cases of lumbar disc herniation with segmental instability,and 16 cases of lumbar spinal stenosis.Operation time,blood loss,and complications were recorded.Visual analog scale scores of lumbago,radiative pain of both lower limbs,and Oswestry disability index scores were evaluated before surgery,3 months after surgery,and the last follow-up.Dural sac cross-sectional area,intervertebral height,and intervertebral fusion were measured and observed. RESULTS AND CONCLUSION:(1)The 34 patients were followed up for 14-36 months,with an average of(21.3±5.2)months.(2)The operation time ranged from 50 to 92 minutes,with an average of(68.5±11.1)minutes.Intraoperative blood loss was 50-170 mL,with an average of(71.6±25.3)mL.(3)Compared with the preoperative results,the visual analog scale scores and Oswestry disability index scores were significantly decreased at 3 months after surgery and at the last follow-up(P<0.001),and the maximum Oswestry disability index scores were improved by nearly 50％.(4)Bone fusion was achieved in all patients during half-year follow-up.The overall complication rate was 21％(7/34),including 1 case of plate displacement,3 cases of cage subsidence,1 case of psoas weakness,and 2 cases of anterior thigh pain.(5)It is concluded that oblique lateral interbody fusion combined with lateral plate fixation for the treatment of lumbar degenerative diseases has the characteristics of less blood loss,short operation time,rapid postoperative recovery,and significant short-term clinical efficacy with the stable support to a certain extent.The long-term curative effect needs further follow-up observation.

BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis （AC） infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum， aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group （n=6） and an infection group （n=6）. The infection group was orally administered 30 third-stage larvae of AC， while the control group received an equal volume of saline. Body weight， visual function， and behavioral scores were measured on post-infection 3， 6， 9， 12， 15， 18， and 21 days to assess neurological alterations. After 21 days， brain tissues were harvested for immunofluorescence staining， hematoxylin-eosin （HE） staining， and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed， and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection， Balb/c mice showed a decline in neurological behavioral scores （P<0.05）. By day 15， visual scores decreased （P<0.05）， and by day 21， significant weight loss （P＜0.001） and mortality were observed. Concurrently， transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes （P<0.001）. HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites， with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE （20：2） was significantly upregulated （P<0.001）， while phosphatidylmethanol （18：0_18：1） was significantly downregulated （P<0.01）. KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis， bile secretion， and cholesterol metabolism， and were involved in key metabolic pathways such as sphingolipid metabolism， neural signal regulation， and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways， modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways， particularly the dysregulation of cholesterol and sphingolipid metabolism， potentially playing a central role in demyelination onset. Furthermore， alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.

ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study systematically analyzed the global research landscape, technological composition, and core patents in the field of networks target and network pharmacology, and proposes further suggestions based on the IncoPat patent citation database and VOSviewer bibliometric network visualization tool. Using patent literature metrics and scientific knowledge mapping method, technological innovation pathways, research hotspots, and future directions in this field were further revealed. In particular, this field is moving towards data-driven, intelligent, and systematic approaches. Patent analysis indicated that most patent applications in this domain focused on traditional Chinese medicine(TCM), which have provided key engineering technical approaches to explore and solve complex problems of TCM. By integrating big data and artificial intelligence technologies, network targets and network pharmacology have conferred high-precision screening and quality control of key components and targets in herbal formulations and prescriptions, accelerating the clinical translation and industrialization of TCM-based new drugs and health products with medicine-food homology. Therefore, it is essential to optimize the patent protection system and establish integrated technology platforms in this field for ensuring the competitiveness of technological achievements in research and clinical application. These efforts will advance the widespread application and high-quality development of TCM modernization, precision medicine, and innovative drug discovery.
Bibliometrics ; Patents as Topic ; Humans ; Medicine, Chinese Traditional ; Network Pharmacology/trends* ; Drugs, Chinese Herbal/pharmacology*

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female