The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

ObjectiveTo explore the current status and issues regarding the application of ancient books in clinical practice guidelines and expert consensus of traditional Chinese medicine （TCM） published in China， and to provide methodological recommendations for the incorporation of ancient books in the development of TCM guidelines. MethodsWe searched China National Knowledge Infrastructure （CNKI）， WanFang Data， VIP， SinoMed， PubMed， Embase， as well as six industry websites including China Association of Chinese Medicine， National Group Standards Information Platform， and Chinese Association of the Integration of Traditional and Western Medicine，etc. TCM clinical practice guidelines or expert consensus issued during January 1st， 2017， to November 26th， 2022 were searched. Clinical practice guidelines or expert consensus that explicitly referred to ancient books were included， and the content regarding the searching for ancient books， sources of access to ancient books， methods of evaluating the level of evidence， methods of evaluating the level of recommendation， and methods of evaluating the evidence for the ancient books were analysed. ResultsA total of 1,215 TCM clinical practice guidelines or expert consensus were retrieved， with 442 articles explicitly mentioning the application of ancient books， including 300 （67.87%） clinical practice guidelines and 142 （32.13%） expert consensus. Sixty of the 442 publications explicitly reported that ancient books searching had been conducted （13.57%）； among these 60 publications 27 （45.00%） explicitly reported ancient books searching strategies， and the most frequent method was manual searching with a total of 24 articles （40.00%）. The most popular search source was Chinese Medical Dictionary， a TCM classics database， with a total of 18 articles. 197 articles （44.57%） explicitly reported the evaluation criteria for the level of evidence， of which 141 articles （71.57%） involved the evaluation criteria for the ancient books； 413 articles （93.44%） mentioned ancient books in the recommendations， and only the source of formula name was mentioned in 409 （99.03%） of the publications. ConclusionThe current application of ancient books in TCM clinical practice guidelines and expert consensus is limited， with issues of non-standard searching and evaluation methods. Standar-dization and uniformity are needed in evidence grading and recommendation standards. Future research should clarify the scope and methods of applying ancient book， emphasize their integration with modern research evidence， and enhance their value and quality in the development of TCM clinical practice guidelines.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Objective To identify the pathogenic variants in 110 patients with essential tremor(ET).Methods Clinical data and peripheral blood samples of ET patients were collected from the Department of Neurology of Peking Union Medical College Hospital and then the genomic DNA was extracted.Dynamic mutation detection of NOTCH2NLC was performed in patients with essential tremor by triplet repeat primed PCR(TP-PCR).Since ET is as-sociated with multiple mechanisms of neuro-degeneration,the next generation sequencing(NGS)panel targeting neu-rodegenerative associating genes were performed to check pathogenic variants in additional genes.Results A total of 110 ET patients and 187 matched control individuals were recruited.The age of onset in the current ET group was(36.30±17.64)years,and 74.8%patients had a family history.No abnormal trinucleotide repeat expansion in NOTCH2NLC was identified.The repeat number of(GGC)n lied within normal ranges between 10－47(average 18.6±5.4).Variants burden analysis showed association of ET with PLA2G6.Three rare variants in four patients in PLA2G6 were identified with unknown significance.Conclusions Dynamic mutations of NOTCH2NLC are uncom-mon in ET patients and that suggests need of more researches for further exploring the genetic mechanism of ET.

Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.

Cadmium sulfide nanoparticles are a new type of semiconductor nanomaterials used in many applications. Studies have shown that cadmium sulfide nanoparticles have toxic effects on the reproductive system， liver， and kidney of the body， and the toxicities are affected by various factors. This paper summarized the current research on the toxicity of cadmium sulfide nanoparticles at home and abroad， and reviewed the latest research progress on the mechanisms of its toxic effects and influencing factors.

Objective:To investigate the complication and compliance of different supine time and the degree of obedience in children with leukemia after intrathecal chemotherapy.Methods:A total of 553 children with leukemia after intrathecal chemotherapy from April 1, 2017 to March 28, 2019 in Beijing Children′s Hospital Affiliated to Capital Medical University were selected. Children who received intrathecal injection from April 1, 2017 to December 31, 2017 were selected as control group(274 cases), from January 1, 2018 to March 28, 2019 were selected as research group(279 cases). The children in research group were supine 2 hours but control group were supine 4 hours after intrathecal. The complications that occurred after injection and within one week after injection and compliance were observed.Results:Finally, 457 children included in this study, there were 235 cases in research group and 222 cases in control group. The number of cases of limb numbness and local pressure reddening in the research group and the control group were 18, 20 and 31, 34, respectively, with statistically significant differences between the two groups( χ2 values were 4.74, 5.07, P<0.05). After intrathecal injection, the patients' compliance with the time of supine removal was completely acceptable to the research group, relatively acceptable, acceptable, and required efforts to adhere to the number of cases were 65, 83, 42, 45, respectively, while the control group were 34, 50, 76, 62, respectively, the differences were significant ( χ2 value was 30.04, P<0.05). Conclusions:Supine for 2 hours after intrathecal injection can reduce the incidence of complications and improve compliance, which is safe and feasible. So, supine for 2 hours after intrathecal injection is recommended.

Bone homeostasis is a relative balance between bone formation and resorption. Signal transducer and activator of transcription 3 (STAT3), which is closely related to bone homeostasis, takes part in multiple intracellular and extracellular signal pathways. STAT3 participates in the process of osteoblast differentiation regulated by several factors. It can also maintain bone homeostasis by regulating the recruitment, differentiation and activation of osteoclasts. In addition, STAT3 is involved in the interaction between osteoblasts and osteoclasts. Patients with STAT3 mutations can have several inherited bone metabolism diseases. Furthermore, STAT3 plays a critical role in load-driven bone remodeling. Mechanical stimulation promotes osteoblast differentiation and bone formation through activating or enhancing STAT3 expression during bone remodeling process. This review summarizes the participation of STAT3 in maintaining bone homeostasis together with its possible mechanisms and discusses the connection between STAT3 and mechanical stimulation in bone remodeling, so as to provide a potential pharmacological target for the treatment of bone diseases.

Objective:To identify the pathogenic gene of a pedigree with symphalangism and to prove the pathogenicity of this locus in vitro.Methods:The clinical data of patients’families were collected at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, peripheral blood was collected and genomic DNA was extracted and NOG, FGF9, GDF5 exon regions were amplified by PCR, and the exon gene mutations were detected by first-generation sequencing technique. The structure of noggin-GDF5 protein complex was simulated in silicon. COS-7 cells were transfected with 5 μg empty plasmid, wild type plasmid and V202G mutant plasmid in vitro. Each group of plasmids was transfected into 3 well cells. The experiment was repeated for 3 times, and the expression of noggin protein was detected by Western blotting. C2C12 cells were also transfected with the above plasmids in vitro for osteogenic differentiation. By applying alkaline phosphatase staining and quantitative assay. Relative expression level of osteoblast-related genes Col1α1, ALP and Runx2 were detected by qRT-PCR. Each group of plasmids was transfected into 3 well cells, and the experiment was repeated for 3 times. All statistical analysis were performed by Prism 6 software. The result were shown as mean±standard deviation, and the comparison between groups was done by unpaired t-test. Data were considered statistically significant when P value is less than 0.05. Results:Both the proband and his mother suffered from symphalangism. The result of Sanger sequencing showed that there was a heterozygous missense mutation of NOG gene (p.V202G) in all patients in this pedigree. No disease-related mutations were detected in FGF9 and GDF5. Computer three-dimensional mechanism simulation showed that the site was located at the α helix. The result of Western blotting showed that the expression of mutant protein was significantly lower than that of wild type. Osteogenic differentiation in vitro showed that the inhibitory effect of V202G mutant protein on osteogenic differentiation decreased. The quantitative result of alkaline phosphatase staining showed that the alkaline phosphatase activity in the vector group was (12.3±0.8) U/L, and the alkaline phosphatase activity in the wild type plasmid group was (2.6±0.3) U/L, which was significantly lower than that in the vector group ( t=11.550, P<0.001). The alkaline phosphatase activity in the mutant plasmid group was (10.8±0.3) U/L. There was no significant difference between the mutant group and the vector group ( t=1.830, P=0.141). The mRNA expression level of osteogenesis-related genes was consistent with the above result . Compared with vector group, the expression of osteogenesis-related genes in wild-type noggin group decreased significantly ALP、 Col1α1 and Runx2 ( t=5.987, 4.498, 4.170; P=0.004, 0.011, 0.014). There was no significant difference between mutant plasmid group and blank vector group in ALP、 Col1α1 and Runx2 ( t=0.433, 0.177, 1.159; P=0.688, 0.868, 0.311). Conclusions:NOG gene c. 605T < G p. V202G is a novel mutation in symphalangism, which is located in the α helix of noggin protein, leading to the decrease of the expression of noggin protein and the manifestation of ankylosis.