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.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

OBJECTIVE To analyze the peak wideband acoustic immittance(WAI)values reflecting the tympanic membrane absorption characteristics during the measurement process in patients with congenital middle ear malformation.METHODS We selected 36 patients diagnosed with congenital middle ear malformation by CT as subjects and evaluated their tympanic membrane absorption characteristics by measuring their acoustic impedance peak pressure.Then,we divided these data into two groups based on the pathological malformation obseved during the surgical process,namely the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group.Calculate the absorption rate values of the tympanic membrane at each frequency corresponding to the peak pressure value of the tympanogram,and the relative area of absorption rate.By conducting independent t-tests,we compared two groups-normal children and patients who had undergone ossicular chain fixation surgery-to analyze the absorption area and peak absorption rate of their tympanic peak pressure values.RESULTS Under peak pressure,there were significant differences(P<0.001)in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with fixed ossicular chain and the normal group.However,there was no difference in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with soft ossicular chain and the normal group.Under peak pressure,the absorption area of the ossicular chain fixation group was significantly lower than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001),while the absorption area of the ossicular chain soft connection group was significantly higher than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001).CONCLUSION When conducting broadband acoustic impedance test,there is a significant difference in the relative area of tympanic membrane absorption rate of acoustic impedance peak pressure between the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group across 226-1 000 Hz.It has application value as a clinical rapid screening and diagnostic tool for middle ear malformations.

OBJECTIVE To investigate the impact of inflammatory cytokines related to different endotypes of chronic rhinosinusitis on the transcriptome of nasal epithelial cells.METHODS Human primary nasal epithelial cells were cultured in vitro,and treated with type 1,type 2,and type 3 inflammatory cytokines IFN-γ(10 ng/ml),IL-4(50 ng/ml),and IL-17A(50 ng/ml),respectively.After 48 hours,cells were collected for RNA extraction and transcriptome analysis.Differentially expressed genes were identified,followed by functional annotation and pathway enrichment analysis.Additionally,common regulated genes among different cytokines were analyzed.RESULTS Treatment of primary nasal epithelial cells with IFN-γ,IL-4,and IL-17A induced significant transcriptomic alterations,with 650,540,and 192 differentially expressed genes,respectively,compared to the control group.Functional annotation and pathway enrichment analysis showed that IFN-γ was mainly associated with defense response to virus,antigen processing and presentation,leukocyte and lymphocyte mediated immunity,and NOD-like receptor signaling pathway;IL-4 was mainly related to the regulation of leukocyte chemotaxis,cell-cell adhesion,ECM-receptor interaction,and MAPK signaling pathway;IL-17A was involved in the regulation of neutrophil chemotaxis,response to molecule of bacterial origin,chemokine signaling pathway,and NF-κB signaling pathway.Genes commonly regulated by IFN-γ,IL-4,and IL-17A were identified,with DUOX2 being upregulated by all the three cytokines.CONCLUSION IFN-γ,IL-4,and IL-17A reshapes the transcriptomic profile of nasal epithelial cells,which mainly regulates signaling pathways related to defense response to virus,leukocyte chemotaxis,and response to bacteria,respectively.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective: To explore the causal association between micronutrients and irritable bowel syndrome (IBS) using a Mendelian randomization (MR) method, so as to provide the evidence for formulating prevention and treatment measures for IBS. Methods: Genome-wide association studies (GWAS) summary data for 14 micronutrients (copper, selenium, zinc, iron, magnesium, calcium, potassium, folate, vitamin C, vitamin D, vitamin E, vitamin B6, vitamin B12, and carotene) were collected from the MRC Integrative Epidemiology Unit at the University of Bristol GWAS data and the UK Biobank data. GWAS data for IBS were obtained from the FinnGen R10 database. A bidirectional two-sample MR analysis was conducted to assess the causal relationships between micronutrients and IBS, with the inverse-variance weighted method as the primary analytical approach. Heterogeneity among instrumental variables was evaluated using Cochran's Q test. Horizontal pleiotropy was assessed via MR-Egger regression and the MR-PRESSO test. The robustness of the results was examined using leave-one-out and funnel plot. Results: Forward MR analysis revealed a statistically significant association between vitamin B12 and IBS (OR=1.523, 95%CI: 1.093-2.213), while no significant associations were observed for the other 13 micronutrients (all P>0.05). Reverse MR analysis showed no significant association between IBS and any of the 14 micronutrients (all P>0.05). Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among the instrumental variables (all P>0.05). The robustness of the findings was supported by leave-one-out and funnel plot. Conclusion Higher vitamin B12 level is associated with an increased risk of IBS, but no reverse causal relationship between vitamin B12 and IBS has been found.

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

Objective To investigate the association between extensive perivascular space(EPVS)burden in different locations and ischemic stroke(IS),its subtypes,and transient ischemic attack(TIA)through Mendelian randomization(MR)analysis.Methods The summary data from large-scale Genome-wide Association Studies(GWAS)and various MR methods were employed.We applied multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness.Subsequently,meta-analysis was utilized to integrate causal relationships between EPVS burden in different locations and IS from various sources.Additionally,reverse MR was employed to observe the impact of various IS types on EPVS burden.Finally,linkage disequilibrium score regression was conducted to assess genetic correlations between exposures and outcomes.Results EPVS burden in both the white matter(OR=1.12,95％CI:1.01-1.25;P=0.04)and basal ganglia(OR=1.57,95％CI:1.30-1.89;P＜0.01)are significant risk factors for IS.EPVS burden in the basal ganglia is also a risk for IS(small-vessel)(OR=4.56,95％CI:2.57-8.27;P=5.95× 10-7).After IS and TIA there seems to be a potential increase in extensive basal ganglia perivascular space burden.Conclusions Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators to predict IS.