ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

OBJECTIVE To provide a reference for revising the safety content of traditional Chinese medicine（TCM） instructions. METHODS A systematic analysis was conducted on the relevant announcements on the revision of TCM instruction from 2013 to 2024， including the year of publication， drug name， drug formulation， announcement release time， and the average number of revisions made to three safety contents （contraindication， adverse drug reaction， and precaution）. According to the report data of national adverse drug reaction monitoring from 2013 to 2024， analyze the proportion of TCM in all adverse drug reactions， the composition ratio of adverse drug reaction of different dosage forms of drugs [TCM injection， oral TCM， other （topical） TCM]. RESULTS From 2013 to 2024， the National Medical Products Administration issued a total of 101 notices on the revision of TCM instruction， involving 241 types of TCM. Among them， there were 163 types of oral TCM， 25 types of TCM injection， and 53 types of other （topical） TCM. There were 3， 10 and 0 types of TCM injection， oral TCM， and other （topical） TCM with missing safety content， respectively. The main source of adverse drug reaction data for TCM injections was post- marketing monitoring data （accounting for 48.00%）； the main source of adverse drug reaction data for oral TCM was monitoring data （accounting for 71.17%）； 73.58% of other （topical） TCM did not mention the source of adverse drug reaction data. The report on national adverse drug reaction monitoring showed that the proportion of all adverse drug reactions of TCM had decreased from 17.3% in 2013 to 12.1% in 2024. Among them， the proportion of adverse drug reaction of TCM injection in the three dosage forms of TCM had decreased from 61.3% in 2015 to 24.6% in 2024， while the proportion of adverse drug reaction of oral TCM in the three dosage forms of TCM had increased from 34.7% in 2015 to 64.0% in 2024. CONCLUSIONS The risk management of TCM safety content has achieved results in China， but still faces three major challenges： strongdependence on passive monitoring， insufficient data traceability， and missing key content. It is urgent to improve safety content by dosage form， optimize data sources， and fully utilize real-world evidence to supplement safety content.

Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P＜0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P＜0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P＜0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.

Methods: (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. Results: (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.

Objective To investigate the value of 4D-CTA combined with SDF-1a/CXCR4 signaling pathway in evaluating the risk of intracranial aneurysm rupture.Methods Fifty patients with unruptured intracranial posterior communicating aneurysms and 50 patients with ruptured intracranial posterior communicating aneurysms were divided into unruptured group 1 and ruptured group 1.All patients underwent 4D-CTA examination and serumSDF-1alevel was detected.Non-ruptured group 1 was followed up for 12 months(After conservative treatment),on this basis,patients with ruptured posterior communicating aneurysms were included in ruptured group 2,and patients with unruptured posterior communicating aneurysms were included in non-ruptured group 2.Results The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in diagnosing ruptured intracranial posterior communicating aneurysms were all greater than 0.70.The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in predicting ruptured intracranial posterior communicating aneurysms in ruptured group 2 were all greater than 0.70.Conclusion 4D-CTA combined with SDF-1acan effectively distinguish ruptured intracranial posterior communicating aneurysms and predict the risk of rupture.

Objective To investigate the impact of SARS-CoV-2 infection on male semen quality through meta-analysis and retrospec-tive study.Methods Literature retrieval was conducted in PubMed,CNKI,Wanfang Database and CBM database.Meta-analysis was performed using Stata 15.0.The male patients meeting the inclusion criteria from our hospital were enrolled as study subjects.General demographic data and semen parameters were collected.Single factor analysis of variance and graphing of semen parameters were con-ducted using GraphPad Prism 9.5.1.The test level was set at 0.05.Results A total of 9 studies involving 267 patients were included in the meta-analysis.There were no significant differences in sperm concentration and survival rate before and after SARS-CoV-2 infec-tion(P＞0.05).Semen volume and percentage of normal morphology significantly increased during 1-3 months after infection(P=0.005,P=0.010),with semen volume recovering to pre-infection level＞3 months later(P＞0.05).Sperm motility and progressive mo-tility increased＞3 months after infection(P=0.046,P=0.045),recovering to pre-infection levels(P=0.099,P=0.098).Sperm DNA fragmentation index may be temporarily elevated within 3 months after infection but gradually decreased＞3 months later.In the retrospective study of 8 cases,there were no statistical differences in semen parameters at different stages compared with pre-infection(P＞0.05),but semen parameters showed a negative trend during＜1 month after infection and recovered to pre-infection levels＞3 months later.Conclusion The results of this laboratory study are basically consistent with the meta-analysis.SARS-CoV-2 infection in males only caused short-term negative effects on sperm morphology,vitality and DNA integrity,but generally recovered to pre-infection levels＞3 months after infection.Due to the limitations of study subjects and sample size,the impact of SARS-CoV-2 infection on male semen quality needs to be further confirmed by long-term large-scale prospective studies.

Objective:To study the risk factors of venous thromboembolism(VTE)and the predictive value of the improved VTE score model to identify the risk of VTE in gynecological surgery patients.Methods:From Janu-ary 1,2020 to December 31,2022,41 patients with VTE after gynecological surgery were selected as the VTE group,and a total of 164 patients with adjacent gynecological surgeries during the same period were selected as the non-VTE group with a ratio of 1 :4.Univariate and multivariate Logistic regression analysis were used to ana-lyze the risk factors of VTE after gynecological surgery,and a modified VTE risk factor rapid assessment model(referred to as the improved VTE score model)was constructed.The receiver operating characteristic(ROC)curve was used to study the predictive value for VTE for in gynecological surgery,and compared with the Caprini score model(Caprini table for short).Results:①Multivatiate Logistic regression analysis showed that there were independent risk factors for postoperative VTE in gynecology surgery(OR＞1,P＜0.05),including age≥60 years,BMI≥28 kg/m2,malignant tumors,surgery time＞3 hours,history of thrombosis,and the increased D-di-mer difference before and after surgery.②The Area under Curve(AUC)of ROC was 0.963 in the improved VTE score model with a Youden index 81.10％,sensitivity 87.80％and specificity 93.29％.The AUC of the Caprini score model was 0.888 with Youden index 63.41％,sensitivity 73.17％and specificity 90.24％.The improved VTE score model the Caprini score model identified 92.68％and 85.37％of VTE patients as high-risk or ex-tremely high-risk,respectively,but the difference was not statistically significant(P＜0.05).Conclusions:More attention should be paid to the six independent risk factors for postoperative VTE in gynecology surgery.The two score models showed a similar identified level.However,the improved VTE score model is more simple and easier to operate,has better practicality,and has certain clinical promotion value.

Objective To analyze the registered clinical trials of headache treated by TCM;To discuss the current research status;To provide reference for the optimization of subsequent clinical trial research plans.Methods All clinical trials of headache treated by TCM were retrieved from the ChiCTR and the ClinicalTrials.The retrieval time was from the database establishment to May 22,2023.The general characteristics,study types,intervention measures and outcome indicators of the trials were analyzed respectively.Results A total of 104 registered studies were included,with the number of registered studies increasing since 2004 and reaching a peak in 2020,involving 25 provincial administrative regions or countries and 69 clinical trial institutions;the funding sources were mainly scientific research funds of universities,national finance and local finance.The research type was mainly intervention research;the designing scheme was mainly randomized parallel control study;the high frequency random method was simple random method;45 registered studies used blind methods.Exploratory studies/pre-trials were the most commonly used in the phases of clinical researches.Most of the registered studies were single-center clinical trials with a total sample size of 9 648 patients.The main interventions were acupuncture and oral Chinese medicines.The high frequency outcome indicators included life quality of score,headache attack frequency,headache attack days and headache severity,etc.There were some problems in outcome indicators,such as non-standard,lack of TCM characteristic advantages,and insufficient patient participation.Conclusion The number of registered studies of headache treated by TCM has increased by year,but there are some problems in design elements,such as random method,blind method,number of research centers,sample size and the setting of outcome indicator.

Objective To discuss the teaching method of staged target teaching(STT)combined with problem-based learning(PBL)in improving the effectiveness of cerebrovascular intervention training.Methods A total of 44 refresher doctors,who received cerebrovascular interventional training at the Department of Interventional Radiology of the First Affiliated Hospital of Zhengzhou University of China between March 2021 and March 2023,were enrolled in this study.Traditional teaching method was adopted for 20 refresher doctors(control group)and STT+PBL teaching method was adopted for the remaining 24 refresher doctors(study group).Before and after the training,the basic theoretical knowledge,operation skill,comprehensive interventional knowledge and the satisfaction survey were compared between the two groups.Results Before training the differences in the basic theoretical knowledge score and learning motivation between the two groups were not statistically significant(P＞0.05).After 6 months training the completion examination score of the study group was significantly better than that of the control group(P＜0.05).Through independently working in clinical practice for one year after training completion,the operation skill,basic theoretical knowledge and comprehensive ability of the study group were remarkably better than those of the control group(P＜0.05).Moreover,the scores of understanding ability,teacher-student interaction,communication skill,clinical thinking ability,self-learning ability,teamwork skill,knowledge mastery degree in the study group were strikingly higher than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion The combination teaching method of STT and PBL can significantly improve the quality and effectiveness of the training on the interventional treatment of cerebrovascular diseases.

This article reviews the current situation, influencing factors, evaluation tools, and intervention measures of sleep disorders in family caregivers of Alzheimer disease (AD) patients, so as to provide reference for improving the sleep quality and quality of life of family caregivers in AD patients.