The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Objective To compare the immediate effects of acupuncture at the true and false acupoints of Yanglingquan on functional connectivity in sensorimotor network(SMN)and dorsal attentional network(DAN)of stroke patients based on functional magnetic resonance imaging(fMRI)technology;To explore the central regulatory mechanism and acupoint specificity of acupuncture in stroke patients with hemiplegia.Methods Totally 20 patients with stroke and hemiplegia were included in the study.fMRI scans of acupuncture at the true and false acupoints of Yanglingquan were performed once every 2 weeks,and motion-related SMN and DAN were extracted by independent component analysis to compare the differences in functional connectivity.Results In SMN,after acupuncture at the Yanglingquan true acupoint,the functional connectivity was enhanced compared with before acupuncture.The enhanced brain areas included the right anterior central gyrus,superior temporal gyrus,inferior frontal gyrus,cuneiform lobe,and anterior cuneiform lobe,as well as the left middle temporal gyrus,occipital gyrus,superior temporal gyrus,parahippocampal gyrus,inferior frontal gyrus,and superior temporal gyrus.After acupuncture at the Yanglingquan false acupoint,the functional connectivity was enhanced compared with before acupuncture.The enhanced brain areas included the right anterior central gyrus,superior frontal gyrus,middle frontal gyrus,and cingulate gyrus,as well as the left medial frontal gyrus,anterior cingulate gyrus,lentiform nucleus,and caudate nucleus.In DAN,after acupuncture at the Yanglingquan true acupoint,the functional connectivity was enhanced compared with before acupuncture.The enhanced brain areas included the right anterior cingulate lobe,superior temporal gyrus,middle temporal gyrus,and occipital gyrus,as well as the left cingulate gyrus,posterior cingulate gyrus,and anterior cingulate lobe.After acupuncture at the Yanglingquan false acupoint,the functional connectivity was enhanced compared with before acupuncture,and the enhanced brain areas included the right anterior cingulate gyrus,left anterior cingulate gyrus,and medial frontal gyrus.Conclusion Acupuncture at Yanglingquan can activate SMN and DAN bilateral related brain regions in patients with hemiplegia,which may promote the recovery of motor function by regulating the initiation and execution of motor activities,and has more acupoint specificity compared with false acupoint.

Yi He Rehabilitation,which is based on traditional Chinese rehabilitation treatments and rehabilitation principles from modern medicine,is effective in staging treatment of post-stroke hemiplegia.This paper systematically discusses the origin and annotation of Yi and He from the perspectives of traditional Chinese medicine and modern medicine.The medicinal connection between Yi and the body and its function is related to unobstructed attunement.Based on the connotation of Yi and He,we believe that the pathogenesis of post-stroke hemiplegia is the comprehensive result of abnormal effects of Yi on the organism at the microscopic level and abnormal effects of He on function at the macroscopic level,featured as tense muscle movement and a pathological process of abnormal motion,including the disturbance of yang qi with body dysfunction,the disorder of spirit with sinews and vessels with diversion,and the variation of brain collateral with physical and mental inconsistency.By inducing relaxation and calmness,Yi He rehabilitation takes effect in staging treatment of post-stroke hemiplegia with characteristic mechanisms.First,by calming ascending yang and relaxing the disordered body in periods of relaxation,it can achieve the maintenance function of the kinematic chain peripherally with passive rehabilitation.Second,by calming the disordered spirit and relaxing the inhibited meridian sinews in spasmodic periods,it can reconstruct the neural plasticity of motor function centrally with assistive rehabilitation.Third,by calming damaged brain collateral and relaxing the impassable zang organs in the recovery period,it can close the central-peripheral-central loop of rehabilitation with active rehabilitation.

Objective To compare the changes of brain voxel-mirrored homotopic connectivity(VMHC)of patients before and after Tai Chi Chuan training based on functional magnetic resonance imaging(fMRI)technology;To discuss the central effect mechanism of Tai Chi Chuan in treating chronic fatigue syndrome(CFS).Methods A total of 25 CFS patients(experiment group)and 27 healthy individuals(control group)were recruited to undergo a 1-month Tai Chi Chuan intervention.All receive one month of Tai Chi Chuan training.Differences in SF-36 scores and VMHC between CFS patients and HCs were compared.Results Before training,the SF-36 scores in the experimental group were significantly lower than those in the control group(P<0.001),and the VMHC in the bilateral inferior occipital gyrus,paracentral lobule,lingual gyrus,insula and superior temporal gyrus brain areas were weakened.After training,the scores of SF-36 in the experimental group significantly increased(P<0.001),and the VMHC in bilateral inferior occipital gyrus,superior temporal gyrus,anterior cuneiform lobe and paracentral lobule were significantly enhanced.The difference in whole brain VMHC was positively correlated with the difference in energy scores in SF-36(r=0.456,P=0.025);some scores of SF-36 in the control group significantly increased(P<0.05),and no significant changes in VMHC were observed in brain regions.Conclusion Tai Chi Chuan can effectively improve the quality of life of patients with CFS.This change may be related to the enhancement of functional connections in brain regions such as inferior occipital gyrus,superior temporal gyrus,precuneus,paracentral lobule,et al.

Objective:To explore the changes of sensorimotor network functional connectivity and coefficient of variation of dyanmic functional connection in stroke patients before and after acupuncture on the left Yanglingquan by means of functional magnetic resonance, and explore the effect mechanism of needle retention.Methods:Twenty five patients with right subcortical cerebral infarction who were hospitalized in Dongzhimen Hospital from September 2014 to September 2019 were selected as the experimental group.In the same period 21 healthy controls were selected as healthy control group. The resting state and acupuncture state images were collected by functional magnetic resonance imaging, and the images were preprocessed. The sensory motor brain network of subjects was extracted by independent component analysis (ICA). The functional connectivity and dynamic changes were compared before and after acupuncture based on the sensory motor network.Results:In the experimental group, there were differences between acupuncture state and resting state in the left inferior parietal lobule. The acupuncture state was stronger than the resting state (P < 0.05, GRF correction). The coordinates of the peak point were (-27, -51, 48), the T value of the peak point was 5.502, and the number of voxels was 12. The variation of dynamic functional connectivity in the sensory motor network of acupuncture state was significantly lower than that in resting state( P<0.05, GRF correction), the peak point coordinates were (-5, -30, 39), the peak T value was -3.152, and the number of voxels is 9.In the control group, there was no significant difference between acupuncture state and resting state in functional connection of sensory motor network, while the difference of sensory motor network and thalamus between acupuncture state and resting state was statistically significant. The intensity of acupuncture state was lower than that of resting state ( P<0.05, GRF correction), the coordinates of peak point were (-12, 3, 6), the T value of peak point was -4.253, and the number of voxels was 183.There was no significant difference in the variation of dynamic functional connectivity in sensory motor network before and after acupuncture. Compared with the healthy control group, the functional connectivity of the experimental group was stronger than that of the healthy control group ( P<0.05, GRF correction). The coordinates of the peak point were (0, 42, 48), the T value of the peak point was 3.988, and the number of voxels was 53.The difference in the resting state of thalamus in the experimental group was weaker than that in the healthy control group ( P< 0.05, GRF correction), the coordinates of the peak point were (- 9, -15, 9), the T value of the peak point was -6.596, and the number of voxels was 101; there was no significant difference in the dynamic functional connectivity variability between the two groups, but there were scattered differences in the resting state ( P<0.05, GRF correction). With age, gender and course of disease as control variables, partial correlation analysis showed that the average functional connectivity strength in the sensory motor network of the experimental group was significantly higher than that of the Fugl Meyer assessment (FMA) of the lower limbs. There was a negative correlation between the scores of FMA. The correlation coefficient between the average functional connectivity in the sensory motor network of acupuncture state and the FMA score of lower extremity was -0.533 ( P=0.011), and the correlation coefficient between the average functional connectivity in the sensory motor network of acupuncture state and FMA score of lower extremity was -0.485 ( P=0.022). Conclusion:The brain function in acupuncture state sensorimotor network of patients with cerebral infarction is different from that in resting state, and this operation mode also has time-related fluctuation changes.

Ischemic stroke (IS) is the result of a combination of multiple risk factors, and its pathogenesis involves multiple systemic physiological and pathological changes. Recent studies have found that the activation of renin-angiotensin system (RAS) is closely related to the development of IS. In this review, we mainly summarize the generation of RAS and pathogenesis of RAS in IS.